637 results on '"French Ministry of Health."'
Search Results
2. Risk of Morbidity, Mortality and Long-term Monitoring of Antiretroviral Treatment in People Living With HIV (AquiVIH-NA)
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National Agency for Research on AIDS and Viral Hepatitis (ANRS), Institut National de la Santé Et de la Recherche Médicale, France, and French Ministry of Health through the COREVIH Aquitaine
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- 2021
3. Spared and impaired abilities in community-dwelling patients entering the severe stage of Alzheimer's disease.
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Gillioz A, Villars H, Voisin T, Cortes F, Gillette-Guyonnet S, Andrieu S, Gardette V, Nourhashémi F, Ousset P, Jouanny P, Vellas B, and Clinical Research Hospital Program of the French Ministry of Health
- Abstract
Background: Comprehensive geriatric assessments of patients entering the severe stage of Alzheimer's disease (AD) are scarce. Methods: Cross-sectional study of 126 patients entering the severe stage of AD in the longitudinal study of REAL.FR cohort. Patients who had a first MMSE score ! 10 during follow-up underwent cognitive, behavioral, nutritional and functional assessment. Support requirements were also evaluated. Results: The best-preserved cognitive abilities were social interaction and response to own name, while praxis, orientation, memory and language showed the largest declines. Regarding independence in daily living, locomotion was best preserved (71% of patients independent) while personal hygiene deteriorated most (15.5%). Behavioral disorders were frequent, and consisted principally of apathy, aberrant motor behavior, and agitation. The Mini Nutritional Assessment showed that 68.5% of patients were malnourished or at risk of malnutrition. Caregiver burden remained mild to moderate in 69.8% of cases. In addition, 80% of patients still lived at home and 71.6% used at least 2 support services, consisting mainly of physician visits and home help. Conclusion: Assessment of remaining cognitive, functional abilities and behavioral disorders at entry to severe AD should help to improve targeted management aimed at preserving these abilities and treating complications, thereby optimizing these patients' quality of life. [ABSTRACT FROM AUTHOR]
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- 2009
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4. Machine Learning–Based Phenogrouping in Mitral Valve Prolapse Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events
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Olivier Huttin, Nicolas Girerd, Antoine Jobbe-Duval, Anne-Laure Constant Dit Beaufils, Thomas Senage, Laura Filippetti, Caroline Cueff, Kevin Duarte, Antoine Fraix, Nicolas Piriou, Damien Mandry, Nathalie Pace, Solena Le Scouarnec, Romain Capoulade, Matthieu Echivard, Jean Marc Sellal, Marie Marrec, Marine Beaumont, Gabriella Hossu, Jean-Noel Trochu, Nicolas Sadoul, Pierre-Yves Marie, Charles Guenancia, Jean-Jacques Schott, Jean-Christian Roussel, Jean-Michel Serfaty, Christine Selton-Suty, Thierry Le Tourneau, Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - équipe Thorax - CHU Nantes (CIC - thorax), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fondation Cœur et Recherche (TLT, 2013, Paris, France), French Ministry of Health 'PHRC-I 2012' (TLT, API12/N/019, Paris, France). T Le Tourneau was supported by an INSERM Translational Research Grant (2012-2016, Paris, France). The STAMP study (OH, CSS) was supported by a grant from the French Ministry of Health (APJ 2015, n°: 2016-A00954-47). Pr Girerd is supported by the French National Research Agency Fighting Heart Failure (ANR-15-RHU-0004), by the French PIA project Lorraine Université d’Excellence GEENAGE (ANR-15-IDEX-04-LUE) programs, and the Contrat de Plan Etat Région Lorraine and FEDER IT2MP, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), and European Project
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[SDV]Life Sciences [q-bio] ,Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine - Abstract
International audience; Background: Structural changes and myocardial fibrosis quantification by cardiac imaging have become increasingly important to predict cardiovascular events in patients with mitral valve prolapse (MVP). In this setting, it is likely that an unsupervised approach using machine learning may improve their risk assessment.Objectives: This study used machine learning to improve the risk assessment of patients with MVP by identifying echocardiographic phenotypes and their respective association with myocardial fibrosis and prognosis.Methods: Clusters were constructed using echocardiographic variables in a bicentric cohort of patients with MVP (n = 429 patients, 54 ± 15 years) and subsequently investigated for their association with myocardial fibrosis (assessed by cardiac magnetic resonance) and cardiovascular outcomes.Results: Mitral regurgitation (MR) was severe in 195 (45%) patients. Four clusters were identified: cluster 1 comprised no remodeling with mainly mild MR, cluster 2 was a transitional cluster, cluster 3 included significant left ventricular (LV) and left atrial (LA) remodeling with severe MR, and cluster 4 included remodeling with a drop in LV systolic strain. Clusters 3 and 4 featured more myocardial fibrosis than clusters 1 and 2 (P < 0.0001) and were associated with higher rates of cardiovascular events. Cluster analysis significantly improved diagnostic accuracy over conventional analysis. The decision tree identified the severity of MR along with LV systolic strain 42 mL/m2 as the 3 most relevant variables to correctly classify participants into 1 of the echocardiographic profiles.Conclusions: Clustering enabled the identification of 4 clusters with distinct echocardiographic LV and LA remodeling profiles associated with myocardial fibrosis and clinical outcomes. Our findings suggest that a simple algorithm based on only 3 key variables (severity of MR, LV systolic strain, and indexed LA volume) may help risk stratification and decision making in patients with MVP. (Genetic and Phenotypic Characteristics of Mitral Valve Prolapse; NCT03884426 and Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse [MVP STAMP]; NCT02879825).
- Published
- 2023
5. Autoantibodies against type I IFNs in patients with critical influenza pneumonia
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Zhang, Qian, Pizzorno, Andrés, Miorin, Lisa, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Manry, Jeremy, Rosain, Jérémie, Philippot, Quentin, Goavec, Kelian, Wroblewski, Isabelle, Husebye, Eystein, Fellay, Jacques, Pothier, Pierre, Morand, Patrice, Navarrete, Nicolás, Franco, José Luis, Uddin, Mohammed J., Carratalà, Jordi, Merino Díaz, Laura, Palomo, Virginia, Seppänen, Mikko R.J., Särekannu, Karita, Aiuti, Alessandro, Retamar Gentil, Pilar, Debette, Stéphanie, Belot, Alexandre, Abel, Laurent, Soler Palacín, Pere, Abad Arranz, Maria, Aguilar Guisado, Manuela, Meyts, Isabelle, Casanova, Jean-Laurent, Gonzalez Granado, Luis L., Butte, Manish J., Itan, Yuval, Escoresca Ortega, Ana, Morio, Tomohiro, Padey, Blandine, Niubó, Jordi, Gallardo Ríos, Rafaela, Lau, Yu-lung, Triantafyllia, Vasiliki, Briones, Marisa, Saker, Kahina, Richard, Pascale, Drolet, Beth A., Espinosa Padilla, Sara, Wauters, Joost, Peigue Lafeuille, Helene, Valiente, Adoración, El Baghdadi, Jamila, Tiberghien, Pierre, Balsera-manzanero, María, Zins, Marie, Hammarström, Lennart, Andreakos, Evangelos, Notarangelo, Luigi D., Prando, Carolina, Condino-neto, Antonio, Dominguez Pinilla, Nerea, Aydillo, Teresa, Okamoto, Keisuke, Soumaré, Aïcha, Karamitros, Timokratis, Medina, Rafael A., Kisand, Kai, Ramírez Duque, Nieves, Feys, Simon, Romero Oraa, Laura, Kuo, Chen-yen, Lei, Wei-te, Quintana Murci, Lluis, Milner, Joshua D., Ku, Cheng-lung, Van De Beek, Diederik, Hsieh, Elena W.Y., Tal, Galit, Fournet, Thomas, Cerba Healthcare Group, Patural, Hugues, Novelli, Giuseppe, Lyon Antigrippe Working Group, Arias, Andrés A., Rovina, Nikoletta, Rodríguez-gallego, Carlos, Puel, Anne, Jouanguy, Emmanuelle, Vinh, Donald C., Henny, Joseph, Mogensen, Trine H., Cobat, Aurélie, Casari, Giorgio, Ramaswamy, Sathishkumar, Abelenda Alonso, Gabriela, Morel, Pascal, Trouillet Assant, Sophie, Tzourio, Christophe, Gallian, Pierre, Reipi Inf Working Group, García Sastre, Adolfo, Constantinescu, Stefan N., Hamzeh Cognasse, Hind, Haerynck, Filomeen, Flores, Carlos, Bousfiha, Ahmed A., García Salum, Tamara, Shahrooei, Mohammed, Slaby, Ondrej, Fragkou, Paraskevi C., Argaud, Laurent, Shcherbina, Anna, Al-muhsen, Saleh, Biggs, Catherine M., Bogunovic, Dusan, Planas, Anna M., Heath, James R., Von Bernuth, Horst, Dufouil, Carole, Bolze, Alexandre, Boeuf, Benoit, Rodríguez Gallego, Carlos, Christodoulou, John, Bondarenko, Anastasiia, Martin, Fernando, Koltsida, Ourania, Sediva, Anna, Ruiz Hernandez, José Juan, Bonneaudeau, Brigitte, Cannet, Dorothée, Etablissement Français Du Sang Study Group, Froidure, Antoine, Laurent, Emilie, Galani, Ioanna Evdokia, Gregersen, Peter K., Lemonnier, Sylvie, Spaan, András N., Darmon, Michael, Grimbacher, Bodo, Del Mar Muñoz Garcia, Maria, Zawadzki, Pawel, Henrickson, Sarah E., O'farrelly, Cliona, Rosa Calatrava, Manuel, Lachaize, Morgane, Okada, Satoshi, Vanker, Martti, Bryceson, Yenan, Ling, Yun, Cooper, Megan A., Lucas, Carrie L., Maniatis, Tom, Romero Vázquez, Gloria María, Mansouri, Davood, Castagnoli, Riccardo, Maródi, László, Mironska, Kristina, Rapti, Vasiliki, Baris Feldman, Hagit, Pozzetto, Bruno, Renia, Laurent, Tancevski, Ivan, Imai, Kohsuke, Ozcelik, Tayfun, Pan-hammarström, Qiang, Al-mulla, Fahd, Pape, Jean W., Etzioni, Amos, Souweine, Bertrand, Perez De Diego, Rebeca, Sánchez Cordero, Maria Jose, Solé Violán, Jordi, Perlin, David S., Queromes, Gregory, Anderson, Mark S., Resnick, Igor, Pesole, Graziano, Su, Helen C., Vanderbeke, Lore, Hagin, David, Jeanne, Michel, Desai, Murkesh, Ferres, Marcela, Sánchez Céspedes, Javier, Perroquin, Magali, Ng, Lisa F.P., Abou Tayoun, Ahmad, Le Corre, Nicole, Snow, Andrew L., Temel, Şehime Gülsün, Tsiodras, Sotirios, Coeuret Pellicer, Mireille, Javouhey, Etienne, Turvey, Stuart E., Covid Human Genetic Effort, Rombauts, Alexander, Zatz, Mayana, Uddin, K.m. Furkan, Fievet, Nathalie, Jarvis, Erich D., Rodríguez De Castro, Felipe, Ferreres, José, Flaig, Amandine, Pujol, Aurora, Cognasse, Fabrice, Sancho Shimizu, Vanessa, Nadif, Rachel, Hanna, Suhair, Constances Cohort, Goldberg, Marcel, Brodin, Petter, Le Got, Stéphane, Ozguler, Anna, Quenot, Jean Pierre, Novelli, Antonio, Cordero, Elisa, Colomb, Benoit, Cupic, Anastasija, Mehlal Sedkaoui, Souad, Sallette, Jérôme, Hernu, Romain, Bustamante, Carlos D., Lina, Bruno, Halwani, Rabih, Casalegno, Jean Sebastien, Schwebel, Carole, Salamanca Rivera, Celia, 3C-Dijon Study, Tangye, Stuart G., Dalgard, Clifton L., Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), European Commission, Square Foundation, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université Paris Cité, Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), Center of Excellence for Influenza Research and Response (US) CEIRR, Agencia Nacional de Investigación y Desarrollo (Chile), Centre National de la Recherche Scientifique (France), Ministère des Solidarités et de la Santé (France), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Sociedad Española de Neumología y Cirugía Torácica, Cabildo de Tenerife, Hellenic Foundation for Research and Innovation, Fondation pour la Recherche Médicale, Fondation Bettencourt Schueller, Ministerio de Ciencia, Innovación y Universidades (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Junta de Andalucía, Research Foundation - Flanders, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 01057100, HORIZON-HLTH-2021-DISEASE-04, MESRI-COVID-19, ANR-10-LABX-62-IBEID, P18-RT-3320, CGIEU0000219140, RTC-2017-6471-1, REIPI RD16/0016/0009, National Institutes of Health, NIH: R01AI088364, R01AI163029, Howard Hughes Medical Institute, HHMI, National Institute of Allergy and Infectious Diseases, NIAID: 75N93021C00014, U19AI135972, U19AI142733, U19AI168631, Jeffrey Modell Foundation, JMF, Glenn Foundation for Medical Research, GFMR: ANRS-COV05, EA20170638020, EQU201903007798, Pfizer, Albert Ellis Institute, AEI, National Center for Advancing Translational Sciences, NCATS: UL1 TR001866, JPB Foundation, JPBF, Horizon 2020 Framework Programme, H2020: 824110, Fondation du Souffle, FdS, College of Natural Resources and Sciences, Humboldt State University, CNRS, Ministerio de Ciencia, Innovación y Universidades, MCIU, Instituto Tecnológico y de Energías Renovables, ITER, SCOR Corporate Foundation for Science, Agence Nationale de la Recherche, ANR: ANR-10-IAHU-01, Institut National de la Santé et de la Recherche Médicale, Inserm, Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT: 1161971, 1212023, Association Nationale de la Recherche et de la Technologie, ANRT, Fonds Wetenschappelijk Onderzoek, FWO: G0B5120N, G0C8517N, G0E8420N, KU Leuven: C16/18/007, Instituto de Salud Carlos III, ISCIII: COV20_01333, COV20_01334, PI12/01565, European Regional Development Fund, ERDF: CB21/13/00006, University of the East, UE, Hellenic Foundation for Research and Innovation, ΕΛ.ΙΔ.Ε.Κ, Université de Paris, SINOVAC outside the submitted work. P. Retamar-Gentil reported personal fees from Merck outside the submitted work. I. Meyts reported grants from CSL-Behring outside the submitted work. E. Andreakos reported grants from Janssen Pharmaceuticals during the conduct of the study. J. Wauters reported grants and personal fees from Pfizer and Gilead outside the submitted work. L. Vanderbeke reported grants from Research Foundation Flanders and non-financial support from Pfizer outside the submitted work. S. Feys reported grants from Pfizer outside the submitted work. J. Casalegno reported 'other' from Pfizer and grants from Sanofi outside the submitted work. M. Rosa-Calatrava reported a patent to WO2016/146836 licensed (Signia Therapeutics), a patent to WO2017/174593 licensed (Signia Therapeutics), and a patent to WO2019/224489 licensed (Signia Therapeutics), and is the co-founder of Signia Therapeutics SAS. S. Trouillet-Assant reported non-financial support from BioMérieux outside the submitted work. A. Garcia-Sastre reported 'other' from Vivaldi Biosciences, Pagoda, Contrafect, Vaxalto, Accurius, Curelab oncology, and Curelab veterinary, personal fees from Avimex, 7Hills, Esperovax, Pfizer, Farmak, Applied Biological Laboratories, Paratus, Pharmamar, Pfizer, and Synairgen, grants from Pfizer, Pharmamar, Blade Therapeutics, Avimex, Accurius, Dyna-vax, Kenall Manufacturing, ImmunityBio, Nanocomposix, Merck, Model Medicines, Atea Pharma, Shenwa Biosciences, Johnson & Johnson, 7 Hills, Hexamer, N-fold LLC, and Applied Biological Laboratories outside the submitted work, in addition, A. Garcia-Sastre had a patent for influenza virus vaccines and uses thereof issued, and invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. J. Casanova reported a patent to PCT/US2021/ 042741 pending. No other disclosures were reported., We thank Dr. Cato Jacobs for her contribution to the sampling of UZLeuven patients in Belgium. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Sci-ence, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmis-sion, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cab-ildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Eu-rope', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University. Author contributions: Q. Zhang, A. Pizzorno, L. Miorin, P., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and, Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Europe', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University., ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), and ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021)
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INTERFERON ,Cerba HealthCare Group ,Immunology ,SEVERE COVID-19 ,Pneumònia ,Autoanticossos ,DETERMINANTS ,IMMUNITY ,Grip ,NEUTRALIZING ANTIBODIES ,3C-Dijon Study ,INFECTION ,Influenza, Human ,Medicine and Health Sciences ,Immunology and Allergy ,Humans ,COVID Human Genetic Effort ,MYASTHENIA-GRAVIS PATIENTS ,Autoantibodies ,REIPI INF Working Group ,Etablissement Français du Sang Study Group ,Yellow Fever Vaccine ,COVID-19 ,Pneumonia ,ALLELES ,Lyon Antigrippe Working Group ,Influenza ,ALPHA ,Settore MED/03 ,Interferon Type I ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,BURDEN ,Constances Cohort - Abstract
Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH; R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y Desarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19”). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009); cofinanced by European Regional Development Fund “A way to achieve Europe”; Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University.
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- 2022
6. Matching Graft Quality to Recipient’s Disease Severity Based on the Survival Benefit in Liver Transplantation
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Jean-Pierre Daurès, Cyrille Feray, Audrey Winter, Daniel Azoulay, Corinne Antoine, Paul Landais, Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Clinique Beau Soleil [Montpellier], University of California [Los Angeles] (UCLA), University of California, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence de la biomédecine [Saint-Denis la Plaine], This work was funded by a grant of the French Ministry of Health and Social Affairs. The present study is part of the 'OPTIMATCH' program funded by the French Ministry of Health within the framework of the national Clinical Research Hospital Program., Bodescot, Myriam, and University of California (UC)
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Adult ,Male ,Quality Control ,medicine.medical_specialty ,Epidemiology ,medicine.medical_treatment ,Population ,lcsh:Medicine ,030230 surgery ,Liver transplantation ,Gastroenterology ,Article ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Disease severity ,Internal medicine ,medicine ,Humans ,Prospective Studies ,education ,lcsh:Science ,education.field_of_study ,Multidisciplinary ,Proportional hazards model ,business.industry ,Liver Diseases ,Statistics ,Hazard ratio ,lcsh:R ,Patient Acuity ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,medicine.disease ,Survival Analysis ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Liver Transplantation ,3. Good health ,Transplantation ,body regions ,Survival benefit ,Liver cirrhosis ,Female ,030211 gastroenterology & hepatology ,lcsh:Q ,business ,Liver cancer - Abstract
Persistent shortage and heterogeneous quality of liver grafts encourages the optimization of donor-recipient matching in liver transplantation (LT). We explored whether or not there was a survival benefit (SB) of LT according to the quality of grafts assessed by the Donor Quality Index (DQI) and recipients’ disease severity, using the Model for End-Stage Liver Disease (MELD) in 8387 French patients wait-listed between 2009 and 2014. SB associated with LT was estimated using the sequential stratification method in different categories of MELD and DQI. For each transplantation, a stratum was created that matched one transplanted patient with all eligible control candidates. Strata were thereafter combined, and a stratified Cox model, adjusted for covariates, was fitted in order to estimate hazard ratios that qualified the SB according to each MELD and DQI sub-group. A significant SB was observed for all MELD and DQI sub-groups, with the exception of high MELD patients transplanted with “high-risk” grafts. More specifically, in decompensated-cirrhosis patients, “high-risk” grafts did not appear to be detrimental in medium MELD patients. Interestingly, in hepatocellular-carcinoma (HCC) patients, a significant SB was found for all MELD-DQI combinations. For MELD exceptions no SB was found. In terms of SB, “low-risk” grafts appeared appropriate for most severe patients (MELD > 30). Conversely, low/medium MELD and HCC patients presented an SB while allocated “high-risk” grafts. Thus, SB based matching rules for LT candidates might improve the survival of the LT population as a whole.
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- 2020
7. Evaluation of the usefulness of ultrasound measurement of the lower uterine segment before delivery of women with a prior cesarean delivery: a randomized trial
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Emmanuel Simon, Isabelle Boutron, Raphaël Porcher, Philippe Deruelle, Elodie Perrodeau, Raoul Desbriere, Yves Ville, Patrick Rozenberg, Norbert Winer, Marie-Victoire Senat, Gilles Kayem, Groupe de Recherche en Obstétrique et Gynécologie, HAL UVSQ, Équipe, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Gynécologie - Obstétrique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Hôpital Saint-Joseph [Marseille], Ministère des Affaires Sociales et de la Santé: PHRC R 12139, This study was funded by a research grant from the French Ministry of Health ( PHRC R 12139 ) and sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique-Hôpitaux de Paris. The sponsor did not participate in the study design, data analysis, data interpretation, or writing of the report. All authors confirm that they had full access to the data in the study and accept responsibility for submitting the article for publication., and This study was funded by a research grant from the French Ministry of Health (PHRC R 12139) and sponsored by the D?partement de la Recherche Clinique et du D?veloppement de l'Assistance Publique-H?pitaux de Paris. The sponsor did not participate in the study design, data analysis, data interpretation, or writing of the report. All authors confirm that they had full access to the data in the study and accept responsibility for submitting the article for publication.
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medicine.medical_specialty ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,medicine.medical_treatment ,[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,law.invention ,Randomized controlled trial ,law ,cesarean delivery ,medicine ,Contraindication ,uterine rupture ,Hysterectomy ,Vaginal delivery ,business.industry ,Obstetrics ,ultrasound ,Absolute risk reduction ,Obstetrics and Gynecology ,medicine.disease ,lower uterine segment thickness ,Confidence interval ,Uterine rupture ,[SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,[SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging ,vaginal birth after cesarean ,Relative risk ,business - Abstract
International audience; Background: The main reason to avoid trial of labor after cesarean delivery is the possibility of uterine rupture. Identifying women at risk is thus an important aim, for it would enable women at low risk to proceed with a secure planned vaginal birth. bjective: To evaluate the impact of proposing mode of delivery based on the ultrasound measurement of the lower uterine segment thickness on a composite outcome of maternal-fetal mortality and morbidity, compared with usual management, among pregnant women with a previous cesarean delivery.Study Design: This multicenter, randomized, controlled, parallel-group, unmasked trial was conducted at 8 referral university hospitals with a neonatal intensive care unit and enrolled 2948 women at 36 weeks 0 days to 38 weeks 6 days of gestation with 1 previous low transverse cesarean delivery and no contraindication to trial of labor. Women in the study group had their lower uterine segment thickness measured by ultrasound. Those with measurements >3.5 mm, were encouraged to choose a planned vaginal delivery, and those with measurements ≤3.5 mm, were encouraged to choose a planned repeat cesarean delivery. This measurement was not taken in the control group; their mode of delivery was decided according to standard management. The primary outcome was a composite criterion comprising maternal mortality, uterine rupture, uterine dehiscence, hysterectomy, thromboembolic disease, transfusion, endometritis, perinatal death, or neonatal encephalopathy. Prespecified secondary outcomes were repeat cesarean deliveries, elective or after trial of labor.Results: The study group included 1472 women, and the control group included 1476 women. These groups were similar at baseline. The primary outcome occurred in 3.4% of the study group and 4.3% of the control group (relative risk, 0.78; 95% confidence interval, 0.54–1.13: risk difference, −1.0%; 95% confidence interval, −2.4 to 0.5). The uterine rupture rate in the study group was 0.4% and in the control group 0.9% (relative risk, 0.43; 95% confidence interval, 0.15–1.19). The planned cesarean delivery rate was 16.4% in the study group and 13.7% in the control group (relative risk, 1.21; 95% confidence interval, 1.00–1.47), whereas the rates of cesarean delivery during labor were 25.1% and 25.0% (relative risk, 1.01; 95% confidence interval, 0.89–1.14) in the study and control groups, respectively.Conclusion: Ultrasound measurements of lower uterine segment thickness did not result in a statistically significant lower frequency of maternal and perinatal adverse outcomes than standard management. However, because this study was underpowered, further research should be encouraged.
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- 2022
8. The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies
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Manry, Jérémy, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Liis, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesús, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Mégarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James, Franco, José Luis, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia, Zhang, Yu, Snow, Andrew, Holland, Steven, Biggs, Catherine, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Anglicheau, Dany, Planas, Anna, Haerynck, Filomeen, Duvlis, Sotirija, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila, Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel, Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam, Kennelly, Sean, Bourke, Nollaig, Halwani, Rabih, Sharif-Askari, Fatemeh Saheb, Dorgham, Karim, Sallette, Jérôme, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald, Erikstrup, Christian, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András, Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard, Mane, Shrikant, Anderson, Mark, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine, Rowen, Lee, Mond, James, Debette, Stéphanie, de Lamballerie, Xavier, Burdet, Charles, Bouadma, Lila, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter, Piemonti, Lorenzo, Rodríguez-Gallego, Carlos, Notarangelo, Luigi, Su, Helen, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles, Tiberghien, Pierre, Zhang, Qian, Casanova, Jean-Laurent, Abel, Laurent, Cobat, Aurélie, Zhang, Peng, Seeleuthner, Yoann, Talouarn, Estelle, Marchal, Astrid, Matuozzo, Daniela, de la Chapelle, Aliénor, Chen, Jie, Chrabieh, Maya, Liu, Dana, Nemirowskaya, Yelena, Cruz, Inés Marín, Materna, Marie, Pelet, Sophie, Thibault, Chloé, Liu, Zhiyong, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Darazam, Ilad Alavi, Albisures, Jonathan Antonio Roblero, Aldave, Juan, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, Allardet-Servent, Jerome, Allende, Luis, Alonso-Arias, Rebeca, Alshahrani, Mohammed, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Feldman, Hagit Baris, Barrou, Benoit, Barzaghi, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P., Bukhari, Huda, Bustamante, Jacinta, Agra, Juan José Cáceres, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew, Clavé, Pere, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, de Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Flores, Carlos, Francois, Bruno, Fumadó, Victoria, Fung, Kitty, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Godínez, Karen Alejandra Cifuentes, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Gut, Marta, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-Ki, Holanda-Peña, María Soledad, Horcajada, Juan, Hraiech, Sami, Humbert, Linda, Hung, Ivan, Iglesias, Alejandro, Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Kanık-Yüksek, Saliha, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Daganou, Maria, Koukaki, Evangelia, Koutsoukou, Antonia, Rapti, Vasiliki, Syrigos, Konstantinos, Król, Zbigniew, Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur, Kwan, Yat Wah M., Kwok, Janette, Lam, David, Conti, Francesca, Pession, Andrea, Lampropoulou, Vicky, Lanternier, Fanny, Bourgeois, Fleur Le, Leo, Yee-Sin, Lopez, Rafael Leon, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Lima, Edson Jose Adrian Bolanos, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José, Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Lye, David, Magnone, Cinthia, Mansouri, Davood, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa Rb, Matthews, Gail, Mayaux, Julien, Mclaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morange, Pierre-Emmanuel, Mordacq, Clémence, Morelle, Guillaume, Mouly, Stéphane, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paz-Artal, Estela, Pedraza-Sánchez, Sigifredo, Gálvez-Romero, José Luis, Pellecer, Nancy Carolina González, Pellegrini, Silvia, Diego, Rebeca Pérez De, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Planas-Serra, Laura, Ploin, Dominique, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rivet, Nadia, Rocamora-Blanch, Gemma, Rodero, Mathieu, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Gallego, Carlos, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Prado, Maria Yolanda Ruiz Del, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril, Scolari, Francesco, Sediva, Anna, Seijo, Luis, Seminario, Analia Gisela, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Shahrooei, Mohammad, Siguret, Virginie, Siouti, Eleni, Smadja, David, Smith, Nikaia, Sobh, Ali, Soler, Catherine, Soler-Palacín, Pere, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, Thorn, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Tsang, Owen, Tserel, Liina, Tso, Eugene, Tucci, Alessandra, Öz, Şadiye Kübra Tüter, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, van den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Veliz, Silvia Patricia Zuniga, Viel, Sébastien, Villain, Cédric, Vilaire-Meunier, Marie, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wu, Alan, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby, Yükselmiş, Ufuk, Ghirardello, Stefano, Zuccaro, Valentina, Andrés, Ana De, van Praet, Jens, Lambrecht, Bart, van Braeckel, Eva, Bosteels, Cédric, Hoste, Levi, Hoste, Eric, Bauters, Fré, Clercq, Jozefien De, Heijmans, Cathérine, Slabbynck, Hans, Naesens, Leslie, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Danielson, Jeffrey, Dobbs, Kerry, Kashyap, Anuj, Ding, Li, Dalgard, Clifton, Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Bettini, Laura Rachele, D’angio, Mariella, Beretta, Ilaria, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Batten, Isabella, Reddy, Conor, Mcelheron, Matt, Noonan, Claire, Connolly, Emma, Fallon, Aoife, Storgaard, Merete, Jørgensen, Sofie, Pedersen, Ole Birger, Sørensen, Erik, Mikkelsen, Susan, Dinh, Khoa Manh, Larsen, Margit Anita Hørup, Paulsen, Isabella Worlewenut, von Stemann, Jakob Hjorth, Hansen, Morten Bagge, Ostrowski, Sisse Rye, Townsend, Liam, Ni Cheallaigh, Cliona, Bergin, Colm, Martin-Loeches, Ignacio, Dunne, Jean, Conlon, Niall, O’farrelly, Cliona, Allavena, Clotilde, Andrejak, Claire, Angoulvant, François, Azoulay, Cecile, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behillill, Sylvie, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bhavsar, Krishna, Bitker, Laurent, Bouscambert-Duchamp, Maude, Paz, Pauline Caraux, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, D’ortenzio, Eric, de Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Duval, Xavier, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farase, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lemaignen, Adrien, Lemee, Véronique, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Machado, Moïse, Malvy, Denis, Mambert, Marina, Manuel, Aldric, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Peigne, Vincent, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Tubiana, Sarah, van der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Jaïs, Jean-Philippe, Pelet, Anna, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, D’enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gomperts-Boneca, Ivo, Hasan, Milena, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly, Lantz, Olivier, Kenny, Rose Anne, Ménager, Mickaël, Michel, Frédérique, Patin, Etienne, Pellegrini, Sandra, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Fontes, Magnus, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew, Alavoine, Loubna, Behillil, Sylvie, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Bourgeon, Marilou, Lefèvre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David, Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave, Dujardin, Romein, Elbers, Paul, Fleuren, Lucas, Geerlings, Suzanne, Geijtenbeek, Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin, Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine, Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe, de Jong, Menno, Lim, Endry, van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther, Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan, van der Poll, Tom, Preckel, Bennedikt, Prins, Jan, Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits, Schinkel, Michiel, Schultz, Marcus, Schrauwen, Femke, Schuurman, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen, Smeele, Patrick, Smit, Marry, Stijnis, Cornelis, Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa, Tuinman, Pieter, van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke, van Vugt, Michèle, Wouters, Dorien, Zwinderman, A., Brouwer, Matthijs, Wiersinga, W. Joost, Vlaar, Alexander, Al-Muhsen, Saleh, Al-Mulla, Fahd, Arias, Andrés, Bogunovic, Dusan, Bolze, Alexandre, Bryceson, Yenan, Bustamante, Carlos, Butte, Manish, Chakravorty, Samya, Christodoulou, John, Constantinescu, Stefan, Cooper, Megan, Desai, Murkesh, Drolet, Beth, El Baghdadi, Jamila, Espinosa-Padilla, Sara, Froidure, Antoine, Henrickson, Sarah, Hsieh, Elena, Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich, Karamitros, Timokratis, Ku, Cheng-Lung, Ling, Yun, Lucas, Carrie, Maniatis, Tom, Maródi, László, Milner, Joshua, Mironska, Kristina, Novelli, Antonio, Novelli, Giuseppe, de Diego, Rebeca Perez, Perez-Tur, Jordi, Arkin, Lisa, Asano, Takaki, Oriol, Roger Colobran, Renia, Laurent, Resnick, Igor, Sancho-Shimizu, Vanessa, Seppänen, Mikko R.J., Shahrooei, Mohammed, Slaby, Ondrej, Tayoun, Ahmad Abou, Ramaswamy, Sathishkumar, Turvey, Stuart, Uddin, K., Uddin, Mohammed, von Bernuth, Horst, Zawadzki, Pawel, Grimbacher, Bodo, Pape, Jean, Perlin, David, Pesole, Graziano, García, Paula Andrea Gaviria, López, Gustavo Andrés Salguero, Rojas-Villaraga, Adriana, Vélez, Verónica Posada, Landinez, Lina Marcela Acevedo, Correales, Luisa Paola Duarte, Gómez, Oscar, Guaqueta, Jeser Santiago Grass, Pérez, Cristian Alejandro Ricaurte, Carrillo, Jorge, Vergara, José Alejandro Daza, Landinez, Sandra, Mantilla, Rubén, Yepes, Jairo David Torres, Ricaurte, Oscar Andrés Briceño, Pérez-Díaz, Carlos, Mateus, Yady Nataly, Navarro, Laura Mancera, Rodríguez, Yhojan, Acosta-Ampudia, Yeny, Monsalve, Diana, Rojas, Manuel, Nadif, Rachel, Goldberg, Marcel, Ozguler, Anna, Henny, Joseph, Lemonnier, Sylvie, Coeuret-Pellicer, Mireille, Got, Stéphane Le, Tzourio, Christophe, Dufouil, Carole, Soumaré, Aïcha, Lachaize, Morgane, Fievet, Nathalie, Flaig, Amandine, Martin, Fernando, Bonneaudeau, Brigitte, Cannet, Dorothée, Gallian, Pierre, Jeanne, Michel, Perroquin, Magali, Hamzeh-Cognasse, Hind, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Hiroshima University, Vall d’Hebron Research Institute (VHIR), University of Tartu, CHU Henri Mondor, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hospital Universitario Infanta Leonor [Madrid], Hospices Civils de Lyon (HCL), Grand Hôpital de l'Est Francilien (GHEF), Vall d'Hebron University Hospital [Barcelona], Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), National Institutes of Health [Bethesda] (NIH), Tokyo Medical and Dental University [Japan] (TMDU), Universitat de Barcelona (UB), Institut National de la Santé et de la Recherche Médicale (INSERM), Biomedical Research Foundation of the Academy of Athens (BRFAA), Institute for Systems Biology [Seattle] (ISB), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidad del Rosario [Bogota], Hospital Universitario de Gran Canaria Dr Negrin, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), Uniformed Services University of the Health Sciences (USUHS), University of British Columbia (UBC), CHU Necker - Enfants Malades [AP-HP], Spanish National Research Council (CSIC), Ghent University Hospital, Goce Delchev University (UGD), Invitae Corporation, Bilkent University [Ankara], Necmettin Erbakan University [Konya, Turquie], Centre Hospitalier Universitaire Hassan II (CHU HII), CHU Ibn Rochd [Casablanca], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institute, Réseau International des Instituts Pasteur (RIIP), Tel Aviv Sourasky Medical Center [Te Aviv], The Feinstein Institute for Medical Research, IRCCS San Raffaele Scientific Institute [Milan, Italie], IRCCS Ospedale San Raffaele [Milan, Italy], Universidade de São Paulo = University of São Paulo (USP), Fundacion Rioja Salud, Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Shupyk National Medical Academy of Postgraduate Education [Kiev] (SNMAPE), I.Horbachevsky Ternopil State Medical University, Ternopil, Ukraine, Hospital Donostia, Garvan Institute of medical research, Sorbonne Université (SU), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Charles University [Prague] (CU), University Hospital Motol [Prague], Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology [Moscow, Russia], The University of Hong Kong (HKU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of La Sabana = Universitad de la Sabana, Hôpital Robert Ballanger [Aulnay-sous-Bois], Sackler Faculty of Medicine, Tel Aviv University (TAU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Tallaght Hospital, Trinity College Dublin, University of Sharjah (UoS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire CERBA [Saint Ouen l'Aumône], King Fahad University, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), McGill University = Université McGill [Montréal, Canada], Aarhus University [Aarhus], Instituto de Pesquisa Pelé Pequeno Principe, Hôpital Jean Verdier [AP-HP], Ecole Polytechnique Fédérale de Lausanne (EPFL), Yale University [New Haven], University of California [San Francisco] (UC San Francisco), University of California (UC), Academy of Athens, Institució Catalana de Recerca i Estudis Avançats (ICREA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), IrsiCaixa (Institut de Recerca de la Sida), Hôpital Foch [Suresnes], Etablissement Français du Sang, EFS, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), George Mason University, Yale University, National Human Genome Research Institute (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), Scientific Committee on Oceanic Research, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondation Bettencourt Schueller, Centro de Investigación Biomédica en Red Enfermedades Raras (España), European Commission, G. Harold & Leila Y. Mathers Foundation, Hospital Universitario Infanta Leonor, National Institute of Allergy and Infectious Diseases (US), National Institute of Dental and Craniofacial Research (US), Estonian Research Council, Al Jalila Foundation, American University of Sharjah, National Health and Medical Research Council (Australia), University of New South Wales (Australia), Regione Lombardia, Instituto de Salud Carlos III, Japan Agency for Medical Research and Development, Sorbonne Université, Université de Bordeaux, National Cancer Institute (US), Research Foundation - Flanders, Hellenic Foundation for Research and Innovation, Sao Paulo Research Foundation, The Meath Foundation, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), INSERM UMRS-1144, Université Paris Cité, Réanimation Médicale et Toxicologique, Hôpital Lariboisière, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the NIH (Grants R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Awards program (Grant UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (Grant S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (Grant ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (Grant EQU201903007798), the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05), the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects, the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e co-morbidità'). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program 'Cohortes et collections de données biologiques.' S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1, AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID), by the Katholieke Universiteit Leuven C1 Grant C16/18/007, by a Flanders Institute for Biotechnology-Grand Challenges - PID grant, by the FWO Grants G0C8517N, G0B5120N, and G0E8420N, and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation., HGID Lab, COVID Clinicians, COVID-STORM Clinicians, NIAID Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, St. James's Hospital, SARS CoV2 Interest Group, French COVID Cohort Study Group, Imagine COVID-Group, Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank Investigators, COVID Human Genetic Effort, CP-COVID-19 Group, CONSTANCES cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement Français du Sang Study group, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-19-CE15-0009,CNSVIRGEN,Déficits immunitaires innés dans les infections sévères du tronc cérébral(2019), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), Manry, J, Bastard, P, Gervais, A, Le Voyer, T, Rosain, J, Philippot, Q, Michailidis, E, Hoffmann, H, Eto, S, Garcia-Prat, M, Bizien, L, Parra-Martínez, A, Yang, R, Haljasmägi, L, Migaud, M, Särekannu, K, Maslovskaja, J, de Prost, N, Tandjaoui-Lambiotte, Y, Luyt, C, Amador-Borrero, B, Gaudet, A, Poissy, J, Morel, P, Richard, P, Cognasse, F, Troya, J, Trouillet-Assant, S, Belot, A, Saker, K, Garçon, P, Rivière, J, Lagier, J, Gentile, S, Rosen, L, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, P, Sene, D, Stepanian, A, Mégarbane, B, Triantafyllia, V, Fekkar, A, Heath, J, Franco, J, Anaya, J, Solé-Violán, J, Imberti, L, Biondi, A, Bonfanti, P, Castagnoli, R, Delmonte, O, Zhang, Y, Snow, A, Holland, S, Biggs, C, Moncada-Vélez, M, Arias, A, Lorenzo, L, Boucherit, S, Anglicheau, D, Planas, A, Haerynck, F, Duvlis, S, Ozcelik, T, Keles, S, Bousfiha, A, El Bakkouri, J, Ramirez-Santana, C, Paul, S, Pan-Hammarström, Q, Hammarström, L, Dupont, A, Kurolap, A, Metz, C, Aiuti, A, Casari, G, Lampasona, V, Ciceri, F, Barreiros, L, Dominguez-Garrido, E, Vidigal, M, Zatz, M, van de Beek, D, Sahanic, S, Tancevski, I, Stepanovskyy, Y, Boyarchuk, O, Nukui, Y, Tsumura, M, Vidaur, L, Tangye, S, Burrel, S, Duffy, D, Quintana-Murci, L, Klocperk, A, Kann, N, Shcherbina, A, Lau, Y, Leung, D, Coulongeat, M, Marlet, J, Koning, R, Reyes, L, Chauvineau-Grenier, A, Venet, F, Monneret, G, Nussenzweig, M, Arrestier, R, Boudhabhay, I, Baris-Feldman, H, Hagin, D, Wauters, J, Meyts, I, Dyer, A, Kennelly, S, Bourke, N, Halwani, R, Sharif-Askari, F, Dorgham, K, Sallette, J, Sedkaoui, S, Alkhater, S, Rigo-Bonnin, R, Morandeira, F, Roussel, L, Vinh, D, Erikstrup, C, Condino-Neto, A, Prando, C, Bondarenko, A, Spaan, A, Gilardin, L, Fellay, J, Lyonnet, S, Bilguvar, K, Lifton, R, Mane, S, Anderson, M, Boisson, B, Béziat, V, Zhang, S, Andreakos, E, Hermine, O, Pujol, A, Peterson, P, Mogensen, T, Rowen, L, Mond, J, Debette, S, de Lamballerie, X, Burdet, C, Bouadma, L, Zins, M, Soler-Palacin, P, Colobran, R, Gorochov, G, Solanich, X, Susen, S, Martinez-Picado, J, Raoult, D, Vasse, M, Gregersen, P, Piemonti, L, Rodríguez-Gallego, C, Notarangelo, L, Su, H, Kisand, K, Okada, S, Puel, A, Jouanguy, E, Rice, C, Tiberghien, P, Zhang, Q, Casanova, J, Abel, L, Cobat, A, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Graduate School, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Gunst, Jan, Acibadem University Dspace, Manry, Jérémy, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Lii, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicola, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesú, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Loui, Sene, Damien, Stepanian, Alain, Mégarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R, Franco, José Lui, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M, Zhang, Yu, Snow, Andrew L, Holland, Steven M, Biggs, Catherine M, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Anglicheau, Dany, Planas, Anna M, Haerynck, Filomeen, Duvlis, Sotirija, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A, Dominguez-Garrido, Elena, Vidigal, Mateu, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Llui, Klocperk, Adam, Kann, Nelli Y, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C, Arrestier, Romain, Boudhabhay, Idri, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H, Kennelly, Sean P, Bourke, Nollaig M, Halwani, Rabih, Sharif-Askari, Fatemeh Saheb, Dorgham, Karim, Sallette, Jérôme, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C, Erikstrup, Christian, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András N, Gilardin, Laurent, Fellay, Jacque, Lyonnet, Stanisla, Bilguvar, Kaya, Lifton, Richard P, Mane, Shrikant, Anderson, Mark S, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelo, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H, Rowen, Lee, Mond, Jame, Debette, Stéphanie, de Lamballerie, Xavier, Burdet, Charle, Bouadma, Lila, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K, Piemonti, Lorenzo, Rodríguez-Gallego, Carlo, Notarangelo, Luigi D, Su, Helen C, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M, Tiberghien, Pierre, Zhang, Qian, Casanova, Jean-Laurent, Abel, Laurent, Cobat, Aurélie, Vougny, Marie-Christine, and Amsterdam Neuroscience - Neuroinfection & -inflammation
- Subjects
Adult ,Male ,Risk ,infection fatality rate ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,autoantibodies ,chronic mucocutaneous candidiasis ,CHRONIC MUCOCUTANEOUS CANDIDIASIS ,Autoimmunity ,IMMUNITY ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Article ,DISEASE ,Basic medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,INFECTION ,Medicine and Health Sciences ,Humans ,IMUNOLOGIA ,Aged ,Autoantibodies ,Aged, 80 and over ,disease ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Multidisciplinary ,SARS-CoV-2 ,type I IFNs ,Age Factors ,COVID-19 ,Type I IFNs ,Middle Aged ,autoantibodie ,immunity ,Antibodies, Neutralizing ,infection ,Infection fatality rate ,Relative risk ,relative risk ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,Interferon Type I ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,type I IFN - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (Grants R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Awards program (Grant UL1 TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (Grant S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (Grant ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (Grant EQU201903007798); the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05); the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects; the Square Foundation; Grandir–Fonds de solidarité pour l’Enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.” S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1; AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID); by the Katholieke Universiteit Leuven C1 Grant C16/18/007; by a Flanders Institute for Biotechnology-Grand Challenges - PID grant; by the FWO Grants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation.
- Published
- 2022
9. Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial
- Author
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Writing Committee for the REMAP-CAP Investigators, Estcourt, Lise J, Turgeon, Alexis F, McQuilten, Zoe K, McVerry, Bryan J, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Arnold, Donald M, Beane, Abigail, Bégin, Philippe, van Bentum-Puijk, Wilma, Berry, Lindsay R, Bhimani, Zahra, Birchall, Janet E, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Buxton, Meredith, Callum, Jeannie L, Chassé, Michaël, Cheng, Allen C, Cove, Matthew E, Daly, James, Derde, Lennie, Detry, Michelle A, De Jong, Menno, Evans, Amy, Fergusson, Dean A, Fish, Matthew, Fitzgerald, Mark, Foley, Claire, Goossens, Herman, Gordon, Anthony C, Gosbell, Iain B, Green, Cameron, Haniffa, Rashan, Harvala, Heli, Higgins, Alisa M, Hills, Thomas E, Hoad, Veronica C, Horvat, Christopher, Huang, David T, Hudson, Cara L, Ichihara, Nao, Laing, Emma, Lamikanra, Abigail A, Lamontagne, François, Lawler, Patrick R, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, MacLennan, Sheila, Marshall, John, McAuley, Daniel F, McDyer, John F, McGlothlin, Anna, McGuinness, Shay, Miflin, Gail, Montgomery, Stephanie, Mouncey, Paul R, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane C, Priddee, Nicole, Purcell, Damian FJ, Reyes, Luis F, Richardson, Peter, Robitaille, Nancy, Rowan, Kathryn M, Rynne, Jennifer, Saito, Hiroki, Santos, Marlene, Saunders, Christina T, Serpa Neto, Ary, Seymour, Christopher W, Silversides, Jon A, Tinmouth, Alan A, Triulzi, Darrell J, Turner, Anne M, van de Veerdonk, Frank, Walsh, Timothy S, Wood, Erica M, Berry, Scott, Lewis, Roger J, Menon, David K, McArthur, Colin, Zarychanski, Ryan, Angus, Derek C, Webb, Steve A, Roberts, David J, Shankar-Hari, Manu, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Investigators, Writing Committee for the REMAP-CAP, Writing Comm REMAP-CAP Investigators, Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institutes of Health, NIH, National Institute of Child Health and Human Development, NICHD, Pittsburgh Foundation, Breast Cancer Research Foundation, BCRF, Bristol-Myers Squibb, BMS, GlaxoSmithKline, GSK, Medtronic, Baxter International, Manitoba Medical Service Foundation, MMSF, CancerCare Manitoba Foundation, CCMF, Wellcome Trust, WT, University of Manitoba, UM, Health Research Board, HRB: PHRC-20-0147, National Blood Authority, NBA, Llywodraeth Cymru, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, CTN 2014-012, Medical Research Council, MRC, National Institute for Health Research, NIHR, Department of Health and Social Care, DH, European Commission, EC: APP194811, National Heart and Lung Institute, NHLI, National Health and Medical Research Council, NHMRC: 2015-06-18, 2016-16-011, APP1101719, APP2002132, Health Research Council of New Zealand, HRC: 16/631, 447335, Monash University, MU, Ministère des Affaires Sociales et de la Santé: 215522, Seventh Framework Programme, FP7, Université Pierre et Marie Curie, UPMC, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Minderoo Foundation, Dr Fitzgerald reported receiving grants from the PREPARE Network and the European Commission. Dr Gordon reported receiving grants from the National Institute for Health Research and receiving personal fees from 30 Respiratory, GlaxoSmithKline, and Bristol Myers Squibb. Dr Gosbell reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Haniffa reported receiving grants from the Wellcome Trust Innovations Project, the Minderoo Foundation, and the UK Research and Innovation African Critical Care Registry Network. Dr Higgins reported receiving grants from the National Health and Medical Research Council, the Minderoo Foundation, and the National Blood Authority. Dr Hills reported receiving grants from the Health Research Council of New Zealand. Dr Hoad reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Horvat reported receiving grants from the National Institute of Child Health and Human Development. Dr Huang reported receiving grants from the Breast Cancer Research Foundation. Dr Lamontagne reported receiving grants from the Canadian Institutes of Health Research. Dr Lawler reported receiving consulting fees from Novartis, Coronna LLC, and Brigham and Women’s Hospital, receiving royalties from McGraw-Hill Publishing, and receiving grants from the Canadian Institutes of Health Research, the LifeArc Foundation, the National Institutes of Health, the Peter Munk Cardiac Centre, the Ted Rogers Centre for Heart Research, the Thistledown Foundation, and the province of Ontario. Dr Lorenzi reported receiving personal fees from Berry Consultants. Dr Marshall reported receiving personal fees from AM-Pharma (data and safety monitoring board chair) and Critical Care Medicine (associate editor). Dr McAuley reported receiving personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Eli Lilly, Vir Biotechnology, Faron Pharmaceuticals, and Sobi, receiving grants from the National Institute for Health Research, Wellcome Trust, Innovate UK, the Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, and holding a patent for an anti-inflammatory treatment that was issued to Queen’s University Belfast. Dr McGlothlin reported receiving grants from the PREPARE Network, the European Commission, and the Global Coalition for Adapative Research. Mr Mouncey reported receiving grants from the European Union, the PREPARE Network, the National Institute for Health Research, and European Union Horizon 2020. Dr Nichol reported receiving grants from the Health Research Board of Ireland and Baxter and receiving personal fees from AM-Pharma. Dr Parke reported receiving grants from Fisher and Paykel Healthcare Ltd. Ms Parker reported receiving grants from Monash University. Mr Richardson reported receiving funding from the Welsh government. Dr Rowan reported receiving grants from the European Commission and the National Institute for Health Research. Dr Saunders reported receiving grants from the PREPARE Network, the European Commission, and the Global Coalition for Adapative Research. Dr Serpa Neto reported receiving personal fees from Drager and Endpoint Health. Dr Tinmouth reported receiving grants and personal fees from the Canadian Blood Services. Ms Turner reported receiving grants from the Health Research Council of New Zealand. Dr van de Veerdonk reported receiving personal fees from Gilead, Sobi, and GlaxoSmithKline. Dr Wood reported receiving grants from the Australian Medical Research Future Fund. Dr S. Berry reported being an employee of Berry Consultants with an ownership role. Dr Lewis reported being an employee of Berry Consultants. Dr Menon reported receiving grants from the National Institute for Health Research. Dr McArthur reported receiving grants from the Health Research Council of New Zealand. Dr Zarychanski reported receiving grants from the Canadian Institutes of Health Research, the University of Manitoba, LifeArc, the Thistledown Foundation, Research Manitoba, the CancerCare Manitoba Foundation, the Victoria General Hospital Foundation, the Peter Munk Cardiac Centre, and the Manitoba Medical Services Foundation. Dr Webb reported receiving grants from the National Health and Medical Research Council and the Minderoo Foundation. Dr Shankar-Hari reported receiving grants from the National Institute for Clinical Research. No other disclosures were reported., nonprofit sponsors: Monash University, Melbourne, Australia (Australasian sponsor), Utrecht Medical Center, Utrecht, the Netherlands (European sponsor), St Michael’s Hospital, Toronto, Ontario, Canada (Canadian sponsor), and the Global Coalition for Adaptive Research, San Francisco, California (US sponsor). This study was additionally funded by grant 602525 FP7-health-2013-innovation-1 from the European Union Platform for European Preparedness Against Reemerging Epidemics, grants APP1101719 and APP1116530 from the Australian National Health and Medical Research Council, grant APP2002132 from the Australian Medical Research Future Fund, grant 16/631 from the New Zealand Health Research Council, grant 447335 from the Canadian Institutes of Health Research COVID-19 Rapid Research, grant 158584 from the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program, grant CTN 2014-012 from the Health Research Board of Ireland, grant PHRC-20-0147 from the French Ministry of Health, and grant 215522 from the Wellcome Trust Innovations Project and funding from the National Institute for Health Research, the Department of Health and Social Care, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the National Institute for Health Research, the National Institute for Health Research Imperial Biomedical Research Centre, the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the Pittsburgh Foundation, and the Minderoo Foundation. The Australian government funds the Australian Red Cross Lifeblood for the provision of blood products and services. The collection of plasma in the United Kingdom was funded by European Union SoHo grants from the Department of Health and Social Care. Dr Turgeon is the Canada Research Chair in Critical Care Neurology and Trauma. Dr McQuilten is supported by emerging leader fellowship APP194811 from the National Health and Medical Research Council. Dr Gordon is funded by research professorship 2015-06-18 from the National Institute for Health Research. Dr Shankar-Hari is funded by clinician scientist fellowship 2016-16-011 from the National Institute for Health Research., In Canada, the trial has been funded by the Canadian Institute of Health Research, Strategy for Patient-Oriented Research (CIHR-SPOR) Innovative Clinical Trials Program Grant (no. 158584) for CAD $1,497,200, for the recruitment of 300 patients., The Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium is funded by the European Union (FP7-HEALTH-2013-INNOVATION-1, grant number 602525). Within the PREPARE consortium, the trial has funding for the recruitment of approximately 4000 patients., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands (RCC-Net)., Funding sources for the REMAP-CAP trial are specified in the core protocol documents. This domain has received domain-specific funding from the Australian Medical Research Future Fund (MRFF)., reported receiving grants from the National Institute for Health Research and European Union Horizon 2020. Dr Turgeon reported receiving grants from the Canadian Institutes of Health Research. Dr McQuilten reported receiving grants from the Australian Medical Research Future Fund. Dr McVerry reported receiving grants from the Pittsburgh Foundation, the Translational Breast Cancer Research Consortium, UPMC Learning While Doing Program, National Heart, Lung, and Blood Institute, and Bayer Pharmaceuticals and receiving personal fees from Boehringer Ingelheim. Dr Annane reported receiving grants from the French Ministry of Health and Solidarity. Dr Arnold reported receiving grants from the Canadian Institutes of Health Research. Ms Beane reported receiving grants and salary support from Wellcome Trust. Ms Bentum-Puijk reported receiving grants from the European Commission and the European Union. Dr L. Berry reported receiving grants from Berry Consultants. Dr Bradbury reported receiving personal fees from Lilly, Bristol Myers Squibb, Pfizer, Bayer, Amgen, Novartis, Janssen, Portola Advisors, and Ablynx. Dr Buxton reported receiving personal fees from the Breast Cancer Research Foundation, Amgen, and Eisai. Dr Callum reported receiving grants from the Canadian Blood Services and Octapharma. Dr Cove reported receiving grants from National University Health System, receiving consulting fees from Medtronic and Baxter, and holding a US patent for removal of carbon dioxide via dialysis. Dr Daly reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Derde reported receiving grants from University Medical Center Utrecht, being a member of the COVID-19 guideline committee of the Surviving Sepsis Campaign/ European Society of Intensive Care Medicine and European Society of Intensive Care Medicine COVID-19 taskforce, and serving as chair of the Dutch intensivists taskforce acute infectious threats. Dr Detry reported receiving grants from the European Union Platform for European Preparedness Against Reemerging Epidemics (PREPARE) consortium, the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, and the UPMC Learning While Doing Program. Dr De Jong reported receiving personal fees from Roche Scientific, Shionogi Scientific, and Janssen., The current regions are: x Europe, with funding from a European Union FP7 grant (FP7-HEALTH-2013-INNOVATION-1, grant number 602525), to support the enrollment of 4000 participants. This funding terminates in 2021. x Australia and New Zealand. In Australia the project has received funding from a NHMRC Project Grant (APP1101719), to support the enrollment of 2000 participants. This funding terminates in December 2021, although some extension may be feasible. In New Zealand the project has received funding from a HRC Programme Grant (16/631), to support the enrollment of 800 participants. This funding terminates in November 2021. x Canada. In Canada the project has received funding for a CIHR grant (158584), to support the enrollment of 300 participants. This funding terminates in 2022. x United States. In the US, funding has been received from UPMC health system for recruitment internally at all UPMC hospitals (>40) and to support a US regional coordinating center. Philanthropic support is being provided through GCAR. Additional funds are being pursued., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Trials Group, the Irish Critical Care, European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), NIHR, National Institute for Health Research, Medical Microbiology and Infection Prevention, AII - Infectious diseases, and Intensive Care Medicine
- Subjects
Male ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,030204 cardiovascular system & hematology ,Logistic regression ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Critical Illness/therapy ,Vasoconstrictor Agents ,030212 general & internal medicine ,Hospital Mortality ,Treatment Failure ,11 Medical and Health Sciences ,Original Investigation ,Mortality rate ,General Medicine ,Middle Aged ,Intensive care unit ,Writing Committee for the REMAP-CAP Investigators ,3. Good health ,Female ,Life Sciences & Biomedicine ,COVID-19/therapy ,Adult ,medicine.medical_specialty ,Randomization ,Respiration, Artificial/statistics & numerical data ,Critical Illness ,ABO Blood-Group System ,03 medical and health sciences ,Medicine, General & Internal ,Internal medicine ,General & Internal Medicine ,medicine ,Humans ,Adverse effect ,COVID-19 Serotherapy ,Aged ,Mechanical ventilation ,Science & Technology ,business.industry ,Immunization, Passive ,Vasoconstrictor Agents/therapeutic use ,COVID-19 ,Odds ratio ,Length of Stay ,Respiration, Artificial ,Logistic Models ,Human medicine ,business - Abstract
Importance The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.Objective To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19.Design, Setting, and Participants The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021.Interventions The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916).Main Outcomes and Measures The primary ordinal end point was organ support–free days (days alive and free of intensive care unit–based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned –1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support–free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support–free days; cardiovascular support–free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events.Results Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support–free days was 0 (IQR, –1 to 16) in the convalescent plasma group and 3 (IQR, –1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR Conclusions and Relevance Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support–free days.Trial Registration ClinicalTrials.gov Identifier: NCT02735707
- Published
- 2021
10. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19
- Author
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Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J., Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G., Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G., Arias, Andres Augusto, Morelle, Guillaume, Kyheng, Christèle, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M., Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E., Pérez de Diego, Rebeca, Keles, Sevgi, Aytekin, Gokhan, Metin Akcan, Ozge, Bryceson, Yenan T., Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C. I. Edvard, Norlin, Anna-Carin, Campbell, Tessa M., Covill, Laura E., Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N., Dalgard, Clifton L., Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P., Bastard, Paul, Notarangelo, Luigi D., Abel, Laurent, Su, Helen C., Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Al-Muhsen, Saleh, Al-Mulla, Fahd, Anderson, Mark S., Andreakos, Evangelos, Arias, Andrés A., Feldman, Hagit Baris, Belot, Alexandre, Biggs, Catherine M., Bogunovic, Dusan, Bondarenko, Anastasiia, Bousfiha, Ahmed A., Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Condino-Neto, Antonio, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Fellay, Jacques, Franco, José Luis, Froidure, Antoine, Gregersen, Peter K., Haerynck, Filomeen, Hagin, David, Halwani, Rabih, Heath, James R., Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Kisand, Kai, Ku, Cheng-Lung, Lau, Yu-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Meyts, Isabelle, Milner, Joshua D., Mironska, Kristina, Mogensen, Trine H., Morio, Tomohiro, Ng, Lisa F.P., O'Farrelly, Cliona, Okada, Satoshi, de Diego, Rebeca Perez, Planas, Anna M., Prando, Carolina, Quintana-Murci, Lluis, Renia, Laurent, Resnick, Igor, Rodríguez-Gallego, Carlos, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänen, Mikko R.J., Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Tancevski, Ivan, Tangye, Stuart G., Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., van de Beek, Diederik, Vinh, Donald C., von Bernuth, Horst, Zatz, Mayana, Zawadzki, Pawel, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, AlKhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Arrestier, Romain, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Boyarchuk, Oksana, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Dalmau, David, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gilardin, Laurent, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Klocperk, Adam, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lagier, Jean-Christophe, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, LAU, Yu-Lung, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Leung, Daniel, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Bolanos Lima, Edson Jose Adrian, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Luyt, Charles-Edouard, Lye, David C, Magnone, Cinthia, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Martinez-Picado, Javier, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morandeira, Francisco, Morange, Pierre-Emmanuel, Mordacq, Cléemence, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paul, Stéphane, Paz-Artal, Estela, Pedraza, Sigifredo, González Pellecer, Nancy Carolina, Pellegrini, Silvia, de Diego, Rebeca Pérez, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Ploin, Dominique, Poissy, Julien, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie S, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Didier, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rigo-Bonnin, Raúl, Rivet, Nadia, Rivière, Jacques G, Rocamora-Blanch, Gemma, Rodero, Mathieu P, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Seijo, Luis, Seminario, Analia Gisela, Sene, Damien, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Solanich, Xavier, Solé-Violán, Jordi, Soler, Catherine, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, Thorn, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Triantafyllia, Vasiliki, Trouillet-Assant, Sophie, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wauters, Joost, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Pelet, Anna, Andrejak, Claire, Angoulvant, François, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behilill, Sylvie, Beluze, Marine, Benkerrou, Dehbia, Bhavsar, Krishna, Bouadma, Lila, Bouchez, Sabelline, Bouscambert, Maude, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Couffignal, Camille, Couffin-Cadiergues, Sandrine, d’Ortenzio, Eric, Debray, Marie-Pierre, Deconinck, Lauren, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Duval, Xavier, Elharrar, Brigitte, Eloy, Philippine, Enouf, Vincent, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Devouge, Eglantine Ferrand, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Khalil, Antoine, Khan, Coralie, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Malvy, Denis, Mambert, Marina, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Nseir, Saad, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Perpoint, Thomas, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rabaud, Christian, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Van Der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Alavoine, Loubna, Behillil, Sylvie, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, van der Werf, Sylvie, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Laine, Fabrice, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefévre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David T.P., Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul, Fleuren, Lucas, Geerlings, Suzanne, Geijtenbeek, Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Koning, Rutger, Lim, Endry H.T., van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan A.I., van der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits C.F.J., Schinkel, Michiel, Schultz, Marcus J., Schrauwen, Femke A.P., Schuurmans, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos), Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Tompkins, Miranda F., Alba, Camille, Hupalo, Daniel N., Rosenberger, John, Sukumar, Gauthaman, Wilkerson, Matthew D., Zhang, Xijun, Lack, Justin, Oler, Andrew J., Dobbs, Kerry, Delmonte, Ottavia M., Danielson, Jeffrey J., Bettini, Laura Rachele, D’Angio, Mariella, Beretta, Ilaria, Imberti, Luisa, Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Neurology, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rockefeller University [New York], Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Helix [San Mateo, CA], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Özçelik, Tayfun, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pathology, Asano, T., Boisson, B., Onodi, F., Matuozzo, D., Moncada-Velez, M., Renkilaraj, M. R. L. M., Zhang, P., Meertens, L., Bolze, A., Materna, M., Korniotis, S., Gervais, A., Talouarn, E., Bigio, B., Seeleuthner, Y., Bilguvar, K., Zhang, Y., Neehus, A. -L., Ogishi, M., Pelham, S. J., Le Voyer, T., Rosain, J., Philippot, Q., Soler-Palacin, P., Colobran, R., Martin-Nalda, A., Riviere, J. G., Tandjaoui-Lambiotte, Y., Chaibi, K., Shahrooei, M., Darazam, I. A., Olyaei, N. A., Mansouri, D., Hatipoglu, N., Palabiyik, F., Ozcelik, T., Novelli, G., Novelli, A., Casari, G., Aiuti, A., Carrera, P., Bondesan, S., Barzaghi, F., Rovere-Querini, P., Tresoldi, C., Franco, J. L., Rojas, J., Reyes, L. F., Bustos, I. G., Arias, A. A., Morelle, G., Kyheng, C., Troya, J., Planas-Serra, L., Schluter, A., Gut, M., Pujol, A., Allende, L. M., Rodriguez-Gallego, C., Flores, C., Cabrera-Marante, O., Pleguezuelo, D. E., Diego, R. P. D., Keles, S., Aytekin, G., Akcan, O. M., Bryceson, Y. T., Bergman, P., Brodin, P., Smole, D., Smith, C. I. E., Norlin, A. -C., Campbell, T. M., Covill, L. E., Hammarstrom, L., Pan-Hammarstrom, Q., Abolhassani, H., Mane, S., Marr, N., Ata, M., Ali, F. A., Khan, T., Spaan, A. N., Dalgard, C. L., Bonfanti, P., Biondi, A., Tubiana, S., Burdet, C., Nussbaum, R., Kahn-Kirby, A., Snow, A. L., Bustamante, J., Puel, A., Boisson-Dupuis, S., Zhang, S. -Y., Beziat, V., Lifton, R. P., Bastard, P., Notarangelo, L. D., Abel, L., Su, H. C., Jouanguy, E., Amara, A., Soumelis, V., Cobat, A., Zhang, Q., Casanova, J. -L., Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University, the St. Giles Foundation, the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at the George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01) and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1, AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by ANR under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX, 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045). A.-L.N. was supported by the Bettencourt Schueller Foundation and the International PhD program of the Imagine Institute. P. Bergman and C.I.E.S received support from the Center for Medical Innovation (CIMED), the Swedish Medical Research Council and the Stockholm County Council (ALF-project). Part of this work was generated within the European Reference Network for rare primary immunodeficiency, autoinflammatory and autoimmune diseases (RITA)., Members of French COVID Cohort Study Group: Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Marie Bartoli5, Romain Basmaci6, Sylvie Behilill7, Marine Beluze8, Dehbia Benkerrou9, Krishna Bhavsar4, Lila Bouadma4, Sabelline Bouchez10, Maude Bouscambert11, Minerva Cervantes-Gonzalez4, Anissa Chair4, Catherine Chirouze12, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric d’Ortenzio5, Marie-Pierre Debray4, Lauren Deconinck4, Dominique Deplanque15, Diane Descamps4, Mathilde Desvallée16, Alpha Diallo5, Alphonsine Diouf13, Céline Dorival9, François Dubos17, Xavier Duval4, Brigitte Elharrar18, Philippine Eloy4, Vincent Enouf7, Hélène Esperou14, Marina Esposito-Farese4, Manuel Etienne19, Eglantine Ferrand Devouge19, Nathalie Gault4, Alexandre Gaymard11, Jade Ghosn4, Tristan Gigante20, Morgane Gilg20, Jérémie Guedj21, Alexandre Hoctin13, Isabelle Hoffmann4, Ikram Houas14, Jean-Sébastien Hulot22, Salma Jaafoura14, Ouifiya Kafif4, Florentia Kaguelidou23, Sabrina Kali4, Antoine Khalil4, Coralie Khan16, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre5, Hervé Le Nagard24, François-Xavier Lescure4, Sophie Letrou4, Yves Levy25, Bruno Lina11, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy26, Marina Mambert13, France Mentré4, Amina Meziane9, Hugo Mouquet7, Jimmy Mullaert4, Nadège Neant24, Duc Nguyen26, Marion Noret27, Saad Nseir17, Aurélie Papadopoulos14, Christelle Paul5, Nathan Peiffer-Smadja4, Thomas Perpoint28, Ventzislava Petrov-Sanchez5, Gilles Peytavin4, Huong Pham4, Olivier Picone6, Valentine Piquard4, Oriane Puéchal29, Christian Rabaud30, Manuel Rosa-Calatrava11, Bénédicte Rossignol20, Patrick Rossignol30, Carine Roy4, Marion Schneider4, Richa Su4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé9, Olivier Terrier11, Jean-François Timsit4, Christelle Tual31, Sarah Tubiana4, Sylvie Van Der Werf7, Noémie Vanel32, Aurélie Veislinger31, Benoit Visseaux4, Aurélie Wiedemann25, Yazdan Yazdanpanah4, ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), Asano, T, Boisson, B, Onodi, F, Matuozzo, D, Moncada-Velez, M, Maglorius Renkilaraj, M, Zhang, P, Meertens, L, Bolze, A, Materna, M, Korniotis, S, Gervais, A, Talouarn, E, Bigio, B, Seeleuthner, Y, Bilguvar, K, Zhang, Y, Neehus, A, Ogishi, M, Pelham, S, Le Voyer, T, Rosain, J, Philippot, Q, Soler-Palacín, P, Colobran, R, Martin-Nalda, A, Rivière, J, Tandjaoui-Lambiotte, Y, Chaïbi, K, Shahrooei, M, Darazam, I, Olyaei, N, Mansouri, D, Hatipoğlu, N, Palabiyik, F, Ozcelik, T, Novelli, G, Novelli, A, Casari, G, Aiuti, A, Carrera, P, Bondesan, S, Barzaghi, F, Rovere-Querini, P, Tresoldi, C, Franco, J, Rojas, J, Reyes, L, Bustos, I, Arias, A, Morelle, G, Christèle, K, Troya, J, Planas-Serra, L, Schlüter, A, Gut, M, Pujol, A, Allende, L, Rodriguez-Gallego, C, Flores, C, Cabrera-Marante, O, Pleguezuelo, D, de Diego, R, Keles, S, Aytekin, G, Akcan, O, Bryceson, Y, Bergman, P, Brodin, P, Smole, D, Smith, C, Norlin, A, Campbell, T, Covill, L, Hammarström, L, Pan-Hammarström, Q, Abolhassani, H, Mane, S, Marr, N, Ata, M, Al Ali, F, Khan, T, Spaan, A, Dalgard, C, Bonfanti, P, Biondi, A, Tubiana, S, Burdet, C, Nussbaum, R, Kahn-Kirby, A, Snow, A, Bustamante, J, Puel, A, Boisson-Dupuis, S, Zhang, S, Béziat, V, Lifton, R, Bastard, P, Notarangelo, L, Abel, L, Su, H, Jouanguy, E, Amara, A, Soumelis, V, Cobat, A, Zhang, Q, and Casanova, J
- Subjects
Male ,SUBSETS ,[SDV]Life Sciences [q-bio] ,Penetrance ,REDUNDANT ,COVID-19 (Malaltia) ,0302 clinical medicine ,Resposta immunitària ,80 and over ,Medicine and Health Sciences ,Medicine ,Young adult ,Child ,X-linked recessive inheritance ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,0303 health sciences ,education.field_of_study ,PYOGENIC BACTERIAL-INFECTIONS ,virus diseases ,Genetic Diseases, X-Linked ,HUMANS ,General Medicine ,Middle Aged ,PROTECTIVE IMMUNITY ,3. Good health ,Pedigree ,Settore MED/03 ,Immune System Diseases ,Genetic Diseases ,Child, Preschool ,Cohort ,medicine.symptom ,SINGLE-STRANDED RNA ,Adult ,Adolescent ,Aged ,Alleles ,COVID-19 ,Humans ,Infant ,Toll-Like Receptor 7 ,Young Adult ,Immunology ,Population ,Asymptomatic ,Article ,03 medical and health sciences ,HOST-DEFENSE ,Immune response ,Allele ,Preschool ,education ,030304 developmental biology ,TOLL-LIKE RECEPTORS ,business.industry ,RECOGNITION ,Proteins ,X-Linked ,medicine.disease ,Pneumonia ,3121 General medicine, internal medicine and other clinical medicine ,PLASMACYTOID DENDRITIC CELLS ,business ,Proteïnes ,030215 immunology - Abstract
Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract. Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University; the St. Giles Foundation; the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS); NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at the George Mason University; the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956); the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01) and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (EQU201903007798); the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects; the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics). The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by ANR under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX; 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045)
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- 2021
11. Potential for recovery between 4 and 8 years after a severe traumatic brain injury. Data from the PariS-TBI longitudinal study
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Eleonore Bayen, Alexis Ruet, Lamiae Grimaldi, S. Azerad, Layide Meaude, Claire Jourdan, Claire Vallat-Azouvi, James Charanton, Philippe Azouvi, Centre Universitaire des Maladies Rénales [CHU Caen] (CUMR Caen), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Raymond Poincaré [AP-HP], Laboratoire de Psychopathologie et Neuropsychologie (LPN), Université Paris 8 Vincennes-Saint-Denis (UP8), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], Pharmacoépidémiologie et maladies infectieuses (PhEMI), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Ressources francilien du traumatisme crânien [Paris], Ministère des Affaires Sociales et de la Santé: AOM04084, The first part of this study and the 8-year evaluation were funded by a grant from the French Ministry of Health (Programme hospitalier de recherche clinique 2004 and 2012, AOM04084) and sponsored by AP?HP (D?partement de la recherche clinique et du d?veloppement). The second part of this study (4-year outcome) was funded by a grant from the Institut de recherche en sant? publique (IRESP)., The first part of this study and the 8-year evaluation were funded by a grant from the French Ministry of Health (Programme hospitalier de recherche clinique 2004 and 2012, AOM04084 ) and sponsored by AP–HP (Département de la recherche clinique et du développement) . The second part of this study (4-year outcome) was funded by a grant from the Institut de recherche en santé publique (IRESP) ., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Adult ,030506 rehabilitation ,Longitudinal study ,medicine.medical_specialty ,Traumatic brain injury ,[SDV]Life Sciences [q-bio] ,Glasgow Outcome Scale ,03 medical and health sciences ,0302 clinical medicine ,Brain Injuries, Traumatic ,Mood ,medicine ,Humans ,Orthopedics and Sports Medicine ,Longitudinal Studies ,Prospective Studies ,Depression (differential diagnoses) ,Univariate analysis ,business.industry ,Rehabilitation ,Odds ratio ,Recovery of Function ,medicine.disease ,3. Good health ,Outcome assessment ,Physical therapy ,Anxiety ,medicine.symptom ,0305 other medical science ,business ,030217 neurology & neurosurgery - Abstract
International audience; Background: Severe traumatic brain injury (TBI) is a leading cause of complex and persistent disability. Yet, long-term change in global functioning and determinants of this change remain unclear. Objectives: This study aimed to assess change in global functioning in the long-term after severe TBI and factors associated with the change. Methods: This was a prospective observational study of an inception cohort of adults with severe TBI in the Paris area (PariS-TBI). Outcome was assessed at 1, 4 and 8 years post-injury. For the included participants (n = 257), change in global outcome between 4 and 8 years was evaluated with the Glasgow Outcome Scale Extended (GOSE) score, and its association with pre-injury, injury-related and post-injury variables was tested with univariate and multivariable analyses. Results: More than half of the 73 participants evaluated at both 4 and 8 years showed global improvement (of at least one point) in GOSE score and an improvement in mood, executive function, and subjective complaints. On univariate analysis, none of the pre-injury, injury or post-injury variables were associated with GOSE score change between 4 and 8 years, except for GOSE score at 4 years (rho = −0.24, P = 0.04). On multivariable analysis, probability of increased GOSE score was associated with more years of education (odds ratio 1.18 [95% confidence interval 1.02–1.37], P = 0.03). The change in GOSE score was significantly correlated with change in Hospital Anxiety Depression Scale score between 4 and 8 years (rho = −0.42, P < 0.001). Conclusions: Most participants with severe TBI in the present sample showed a late improvement (4 to 8 years post-injury) in global functioning. Of the socio-demographic and injury-related factors, only more years of education was associated with improvement in global functioning. Decreased anxiety and depression symptoms were associated with improved global functioning. Targeting interventions to enhance resilience may be the most effective in the long-term after severe TBI.
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- 2021
12. Perinatal outcome after planned vaginal delivery in monochorionic compared with dichorionic twin pregnancy
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François Goffinet, M. V. Senat, Loïc Sentilhes, Norbert Winer, Charles Garabedian, Patrick Rozenberg, Elie Azria, Christophe Vayssière, Diane Korb, Thomas Schmitz, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Maternité Port-Royal [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), DHU Risques Et Grossesse, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AOM2012 Ministère des Affaires Sociales et de la Santé, The authors thank URC-CIC Paris Descartes Necker/Cochin (Laurence Lecomte) for the study implementation, monitoring and data management. This work was funded by a grant from the French Ministry of Health (PHRC, AOM2012). L.S. carried out consultancy work and was a lecturer for Ferring Laboratories in the previous 3 years., and The authors thank URC‐CIC Paris Descartes Necker/Cochin (Laurence Lecomte) for the study implementation, monitoring and data management. This work was funded by a grant from the French Ministry of Health (PHRC, AOM2012).
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Adult ,medicine.medical_specialty ,Population ,Twins ,Reproductive technology ,[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,Labor Presentation ,03 medical and health sciences ,0302 clinical medicine ,Obstetrics and gynaecology ,dichorionic twins ,Pregnancy ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,030212 general & internal medicine ,education ,Perinatal Mortality ,Twin Pregnancy ,education.field_of_study ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,business.industry ,Vaginal delivery ,Obstetrics ,Cephalic presentation ,Infant, Newborn ,Pregnancy Outcome ,Obstetrics and Gynecology ,Gestational age ,Chorion ,General Medicine ,neonatal morbidity ,twin pregnancy ,Delivery, Obstetric ,Obstetric Labor Complications ,3. Good health ,Reproductive Medicine ,Vagina ,monochorionic twins ,Pregnancy, Twin ,Female ,planned vaginal delivery ,France ,Monochorionic twins ,business - Abstract
OBJECTIVE To assess, according to chorionicity, the perinatal outcome of twin pregnancy in which vaginal delivery is planned. METHODS JUMODA (JUmeaux MODe d'Accouchement) was a national prospective population-based cohort study of twin pregnancies, delivered in 176 maternity units in France, from February 2014 to March 2015. In this planned secondary analysis, we assessed, according to chorionicity, the perinatal outcome of twin pregnancies, in which vaginal delivery was planned, that delivered at or after 32 weeks of gestation with the first twin in cephalic presentation. In order to select a population with well-recognized indications for planned vaginal delivery, we applied the same exclusion criteria as those in the Twin Birth Study, an international randomized trial. Monochorionic twin pregnancies with twin-to-twin transfusion syndrome or twin anemia-polycythemia sequence were defined as complicated and were excluded. The primary outcome was a composite of intrapartum mortality and neonatal morbidity and mortality. Multivariable logistic regression models were used to control for potential confounders. Subgroup analyses were conducted according to birth order (first or second twin) and gestational age at delivery (
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- 2021
13. Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies
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Fulvio Ricceri, Joseph A. Rothwell, Amanda J. Cross, Graham G. Giles, Elisabete Weiderpass, Tilman Kühn, Emily Sonestedt, Yi Yang, Rudolf Kaaks, Valeria Pala, Anna Karakatsani, Dallas R. English, Rosario Tumino, Pilar Amiano, Antonia Trichopoulou, John L. Hopper, Leila Lujan-Barroso, Allison M. Hodge, Bengt Wallner, Ruth C. Travis, María Dolores López, Anne Tjønneland, Hazel M. Mitchell, Kostas Tsilidis, Domenico Palli, Harindra Jayasekara, Elio Riboli, Antonio Agudo, Robin Room, Heiner Boeing, Eva Ardanaz, Bas Bueno-de-Mesquita, Torkjel M. Sandanger, Pietro Ferrari, Robert J. MacInnis, Susana Merino, Andrew Haydon, Eleni Peppa, Marie-Christine Boutron-Ruault, Salvatore Panico, María José Sánchez, Marc J. Gunter, Hanna Sternby, Roger L. Milne, Gianluca Severi, Ana Lucia Mayen-Chacon, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), VicHealth Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT Medical Research Council, MRC: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1 British Heart Foundation, BHF Department of Health and Social Care, DH Cancer Research UK, CRUK: C570/ A16491, C8221/A19170, C864/A14136 World Cancer Research Fund, WCRF Food Standards Agency, FSA Stroke Association European Commission, EC National Health and Medical Research Council, NHMRC: 1074383, 209057, 396414, GNT1163120 Cancer Council Victoria Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Vetenskapsrådet, VR Consiglio Nazionale delle Ricerche, CNR Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Rijksinstituut voor Volksgezondheid en Milieu, RIVM Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Foundation for Alcohol Research and Education, FARE Hellenic Health Foundation, HHF, Australian National Health and Medical Research Council, Grant/Award Numbers: 1074383, 209057, 396414, GNT1163120, Cancer Council Victoria (Australia), Cancer Research UK, Grant/Award Numbers: C570/ A16491, C8221/A19170, C864/A14136, Catalan Institute of Oncology ‐ ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission (Directorate General for Health and Consumer Affairs), Foundation for Alcohol Research and Education (Australia), French Ministry of Health, Grant/Award Number: Grant GR‐IARC‐2003‐09‐12‐01, Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Santé et de la Recherche Médicale (France), Italian Association for Research on Cancer and the National Research Council (Italy), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, Medical Research Council (UK), Grant/Award Numbers: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1, Mutuelle Générale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK), Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), the Federal Ministry of Education and Research (Germany), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Institut Gustave Roussy Funding information, We thank Carine Biessy and Bertrand Hemon for their technical contribution to EPIC data used in this work. We are also grateful to all the EPIC participants who have been part of the project, and to the many members of the study teams who enabled this research. We thank the original MCCS investigators and the diligent team, who recruited the participants and who continue working on follow‐up, for their contribution. We also express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study, the Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ‐ ICO (Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). MCCS cohort recruitment was funded by Cancer Council Victoria ( https://www.cancervic.org.au/ ) and VicHealth ( https://www.vichealth.vic.gov.au/ ). The MCCS was further supported by Australian National Health and Medical Research Council (NHMRC) ( https://www.nhmrc.gov.au/ ) grants 209057, 396414 and 1074383, and ongoing follow‐up and data management has been funded by Cancer Council Victoria since 1995. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. Harindra Jayasekara is supported by NHMRC grant GNT1163120. John L. Hopper is a NHMRC Senior Principal Research Fellow. Yi Yang is supported by a Melbourne Research Scholarship from the University of Melbourne. Robin Room's position was funded by the Foundation for Alcohol Research and Education. The sponsors had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and and decision to submit the manuscript for publication.
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Male ,Cancer Research ,Gastroenterology ,0302 clinical medicine ,Prospective Studies ,Stomach cancer ,Prospective cohort study ,stomach cancer ,biology ,Stomach ,Incidence ,Hazard ratio ,Smoking ,cardia cancer ,Cardia cancer ,Middle Aged ,Lifetime alcohol intake ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,Europe ,medicine.anatomical_structure ,Oncology ,Drinking of alcoholic beverages ,030220 oncology & carcinogenesis ,Consum d'alcohol ,Female ,Life Sciences & Biomedicine ,Cohort study ,Adult ,medicine.medical_specialty ,Alcohol Drinking ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Helicobacter Infections ,noncardia cancer ,03 medical and health sciences ,Stomach Neoplasms ,Internal medicine ,medicine ,Humans ,1112 Oncology and Carcinogenesis ,Oncology & Carcinogenesis ,Aged ,Science & Technology ,Helicobacter pylori ,EPIC ,lifetime alcohol intake ,MCCS ,business.industry ,Càncer d'estómac ,Kirurgi ,Australia ,Cancer ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Noncardia cancer ,medicine.disease ,biology.organism_classification ,Surgery ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition - Abstract
Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences., National Health and Medical Research Council of Australia 1074383 209057 396414 GNT1163120, Canadian Institutes of Health Research (CIHR) Cancer Council Victoria, Cancer Research UK C570/A16491 C8221/A19170 C864/A14136, Catalan Institute of Oncology - ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission European Commission Joint Research Centre, Foundation for Alcohol Research and Education (Australia), French Ministry of Health GR-IARC-2003-09-12-01, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Junta de Andalucía, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Sante et de la Recherche Medicale (Inserm), Consiglio Nazionale delle Ricerche (CNR), Associazione Italiana per la Ricerca sul Cancro (AIRC), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC-UU_12015/1 MR/M012190/1 MR/N003284/, Mutuelle Generale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association (UK), British Heart Foundation, Department of Health (UK), Food Standards Agency (UK), Wellcome Trust, Swedish Cancer Society, Swedish Scientific Council (Sweden), Regional Government of Skane (Sweden), Federal Ministry of Education & Research (BMBF), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), Institut Gustave Roussy
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- 2021
14. Hypoglycemia and Glycemic Control With Glyburide in Women With Gestational Diabetes and Genetic Variants of Cytochrome P450 2C9 and/or OATP1B3
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Laurent Mandelbrot, Hanane Bouchghoul, Céline Verstuyft, Laurent Becquemont, Alexandra Letourneau, Jean Bouyer, Marie-Victoire Senat, Nathalie Bourcigaux, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Antoine Béclère [Clamart], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Génétique Moléculaire Pharmacogénétique et Hormonologie [CHU Bicêtre], British Society of Criminology, BSC: BB-0033-00089 Ministère des Affaires Sociales et de la Santé, This study was funded by a research grant from the French Ministry of Health and was sponsored by Paris Public Hospitals (AP-HP, Assistance Publique-H?pitaux de Paris), via its Clinical Research Department. The authors thank David Marsh, BSc (Biophysics, First Class Honours, University of Leeds, UK) PhD (Biophysics, King?s College London, UK), freelance copyeditor/proofreader, for language editing. We thank Elodie Dupuis and Solene Fabre for their technical assistance for the biobank. The biobank INDAO is stored in CRB Paris South (BRIF: BB-0033-00089)., and This study was funded by a research grant from the French Ministry of Health and was sponsored by Paris Public Hospitals (AP‐HP, Assistance Publique‐Hôpitaux de Paris), via its Clinical Research Department.
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Adult ,medicine.medical_specialty ,Genotype ,Glycemic Control ,Hypoglycemia ,030226 pharmacology & pharmacy ,03 medical and health sciences ,Solute Carrier Organic Anion Transporter Family Member 1B3 ,0302 clinical medicine ,Pharmacokinetics ,Pregnancy ,Internal medicine ,Glyburide ,medicine ,Humans ,Hypoglycemic Agents ,Pharmacology (medical) ,Allele ,CYP2C9 ,Glycemic ,Cytochrome P-450 CYP2C9 ,Pharmacology ,Polymorphism, Genetic ,Dose-Response Relationship, Drug ,business.industry ,Genetic Variation ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,medicine.disease ,3. Good health ,Gestational diabetes ,Diabetes, Gestational ,Endocrinology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
International audience; Glyburide is mainly metabolized by the cytochrome P450 2C9 (CYP2C9) enzyme and enters the liver via the transporter OATP1B3. The variants OATP1B3*4 (699 G>A; rs7311358) and CYP2C9*2 and *3 are known to have a significant influence on the hepatic uptake and metabolism of glyburide, with lower clearance than in the wild type. In an ancillary study of the INDAO trial, we selected 117 pregnant women with gestational diabetes treated by glyburide and assessed the role of the combined CYP2C9 and OATP1B3 genetic polymorphisms in hypoglycemia and glycemic control. Three groups were constituted: (1) the wild-type genotype group (wild-type allele genotype for both CYP2C9*1 and OATP1B3*1 (699G)), (2) the intermediate group (carriers of CYP2C9*2 allele or OATP1B3*4 (699G>A) heterozygous), and (3) the variant group (carriers of CYP2C9*3 allele and/or OATP1B3*4 (699G>A) homozygous variant). We found that the risk of hypoglycemia was significantly higher in the variant genotype at the second week of treatment: 20.0% (4/20) vs. 8.1% (3/37) in the intermediate group and 4.1% (2/49) in the wild-type genotype group (P = 0.03). The last daily dose of glyburide during pregnancy was lower for patients in the variant genotype group: 4.7 mg (SD 3.5) vs. 8.7 mg (SD 5.7) in the wild-type group and 5.7 mg (SD 3.7) in the intermediate group (P
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- 2021
15. Factors Associated with Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial
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Aurélien, Dinh, Clara, Duran, Jacques, Ropers, Frédérique, Bouchand, Benjamin, Davido, Laurène, Deconinck, Morgan, Matt, Olivia, Senard, Aurore, Lagrange, Guillaume, Mellon, Ruxandra, Calin, Sabrina, Makhloufi, Victoire, de Lastours, Emmanuel, Mathieu, Jean-Emmanuel, Kahn, Elisabeth, Rouveix, Julie, Grenet, Jennifer, Dumoulin, Thierry, Chinet, Marion, Pépin, Véronique, Delcey, Sylvain, Diamantis, Daniel, Benhamou, Virginie, Vitrat, Marie-Christine, Dombret, Didier, Guillemot, Bertrand, Renaud, Yann-Erick, Claessens, José, Labarère, Philippe, Aegerter, Jean-Pierre, Bedos, Anne-Claude, Crémieux, Marie, Poupard, Université Paris-Saclay, Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP), Unité de Recherche Clinique des hôpitaux Pitié-Salpêtrière – Charles Foix [CHU Pitié Salpêtrière] (URC PSL-CFX), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Grand Hôpital de l'Est Francilien (GHEF), Centre Hospitalier René Dubos [Pontoise], Hôpital Beaujon [AP-HP], Hôpital Foch [Suresnes], Service de médecine interne [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpital Ambroise Paré [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier de Melun (CHM), CHU Rouen, Normandie Université (NU), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Service de médecine d'urgence [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier Princesse Grace, Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Versailles André Mignot (CHV), Hopital Saint-Louis [AP-HP] (AP-HP), This study was supported by grant PHRC 2005AOM05031 from the French Ministry of Health and sponsored by grant PO50607 from the DRCI of Versailles., HAL UVSQ, Équipe, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Pfizer, Ministère des Affaires Sociales et de la Santé: PO50607, Funding/Support: This study was supported by grant PHRC 2005AOM05031 from the French Ministry of Health and sponsored by grant PO50607 from the DRCI of Versailles., and Conflict of Interest Disclosures: Dr Crémieux reported receiving grants from the French Ministry of Health during the conduct of the study and from Pfizer outside the submitted work. No other disclosures were reported.
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Male ,medicine.medical_specialty ,Population ,Placebo ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Community-acquired pneumonia ,Randomized controlled trial ,law ,Risk Factors ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Treatment Failure ,education ,Aged ,Original Investigation ,Aged, 80 and over ,Univariate analysis ,education.field_of_study ,Duration of Therapy ,business.industry ,Research ,General Medicine ,Odds ratio ,Pneumonia ,Middle Aged ,medicine.disease ,3. Good health ,Community-Acquired Infections ,Hospitalization ,Online Only ,Infectious Diseases ,030228 respiratory system ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Complication ,business - Abstract
Key Points Question What are the risk factors for treatment failure in patients with community-acquired pneumonia (CAP) who reached clinical stability after 3 days of β-lactam treatment? Findings In this secondary analysis of a randomized clinical trial that included 291 adults, only male sex and age were associated with failure in the multivariable analysis. These results were independent of antibiotic treatment duration and biomarker levels. Meaning In this study, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, male sex and age were associated with higher risk of failure, suggesting that these factors should be taken in account in the treatment of patients with the condition., Importance Failure of treatment is the most serious complication in community-acquired pneumonia (CAP). Objective To assess the potential risk factors for treatment failure in clinically stable patients with CAP. Design, Setting, and Participants This secondary analysis assesses data from a randomized clinical trial on CAP (Pneumonia Short Treatment [PTC] trial) conducted from December 19, 2013, to February 1, 2018. Data analysis was performed from July 18, 2019, to February 15, 2020. Patients hospitalized at 1 of 16 centers in France for moderately severe CAP who were clinically stable at day 3 of antibiotic treatment were included in the PTC trial and analyzed in the per-protocol trial population. Interventions Patients were randomly assigned (1:1) on day 3 of antibiotic treatment to receive β-lactam (amoxicillin-clavulanate [1 g/125 mg] 3 times daily) or placebo for 5 extra days. Main Outcomes and Measures The main outcome was failure at 15 days after first antibiotic intake, defined as a temperature greater than 37.9 °C and/or absence of resolution or improvement of respiratory symptoms and/or additional antibiotic treatment for any cause. The association among demographic characteristics, baseline clinical and biological variables available (ie, at the first day of β-lactam treatment), and treatment failure at day 15 among the per-protocol trial population was assessed by univariate and multivariable logistic regressions. Results Overall, 310 patients were included in the study; this secondary analysis comprised 291 patients (174 [59.8%] male; mean [SD] age, 69.6 [18.5] years). The failure rate was 26.8%. Male sex (odds ratio [OR], 1.74; 95% CI, 1.01-3.07), age per year (OR, 1.03; 95% CI, 1.01-1.05), Pneumonia Severe Index score (OR, 1.01; 95% CI, 1.00-1.02), the presence of chronic lung disease (OR, 1.85; 95% CI, 1.03-3.30), and creatinine clearance (OR, 0.99; 95% CI, 0.98-1.00) were significantly associated with failure in the univariate analysis. When the Pneumonia Severe Index score was excluded to avoid collinearity with age and sex in the regression model, only male sex (OR, 1.92; 95% CI, 1.08-3.49) and age (OR, 1.02; 95% CI, 1.00-1.05) were associated with failure in the multivariable analysis. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, only male sex and age were associated with higher risk of failure, independent of antibiotic treatment duration and biomarker levels. Another randomized clinical trial is needed to evaluate the impact of treatment duration in populations at higher risk for treatment failure., This secondary analysis of a randomized clinical trial assesses treatment failure risk factors in patients with community-acquired pneumonia who reached clinical stability after 3 days of β-lactam treatment.
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- 2021
16. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19
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Bastard, P., Rosen, L. B., Zhang, Q., Michailidis, E., Hoffmann, H. -H., Zhang, Y., Dorgham, K., Philippot, Q., Rosain, J., Beziat, V., Manry, J., Shaw, E., Haljasmagi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A. A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A. N., Delmonte, O. M., Abers, M. S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R. P., Vasse, M., Smadja, D. M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D. C., Tangye, S. G., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M. C., Boisson-Dupuis, S., Rodriguez-Gallego, C., Vogt, G., Mogensen, T. H., Oler, A. J., Gu, J., Burbelo, P. D., Cohen, J. I., Biondi, A., Bettini, L. R., Dangio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E. S., Fusco, F., Ursini, M. V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G. L., Duval, X., Ghosn, J., Tsang, J. S., Goldbach-Mansky, R., Kisand, K., Lionakis, M. S., Puel, A., Zhang, S. -Y., Holland, S. M., Gorochov, G., Jouanguy, E., Rice, C. M., Cobat, A., Notarangelo, L. D., Abel, L., H. C., Su, Casanova, J. -L., Arias, A. A., Boisson, B., Boucherit, S., Bustamante, J., Chbihi, M., Chen, J., Chrabieh, M., Kochetkov, T., Le Voyer, T., Liu, D., Nemirovskaya, Y., Ogishi, M., Papandrea, D., Patissier, C., Rapaport, F., Roynard, M., Vladikine, N., Woollett, M., Zhang, P., Kashyap, A., Ding, L., Bosticardo, M., Wang, Q., Ochoa, S., Liu, H., Chauvin, S. D., Stack, M., Koroleva, G., Bansal, N., Dalgard, C. L., Snow, A. L., Abad, J., Aguilera-Albesa, S., Akcan, O. M., Darazam, I. A., Aldave, J. C., Ramos, M. A., Nadji, S. A., Alkan, G., Allardet-Servent, J., Allende, L. M., Alsina, L., Alyanakian, M. -A., Amador-Borrero, B., Amoura, Z., Antoli, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H. B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinieres, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, M., Borie, R., Bousfiha, A. A., Bouvattier, C., Boyarchuk, O., Bueno, M. R. P., Agra, J. J. C., Calimli, S., Capra, R., Carrabba, M., Casasnovas, C., Caseris, M., Castelle, M., Castelli, F., de Vera, M. C., Castro, M. V., Chalumeau, M., Charbit, B., Cheng, M. P., Clave, P., Clotet, B., Codina, A., Colkesen, F., Colobran, R., Comarmond, C., Corsico, A. G., Darley, D. R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Di Sabatino, A., Diehl, J. -L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M. H., Emiroglu, M., Erdeniz, E. H., Aytekin, S. E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M. F., Flores, C., Francois, B., Fumado, V., Solis, B. G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M. G., Girona-Alarcon, M., Goffard, J. -C., Gok, F., Gonzalez-Montelongo, R., Guerder, A., Gul, Y., Guner, S. N., Gut, M., Halwani, R., Hammarstrom, L., Hatipoglu, N., Hernandez-Brito, E., Holanda-Pena, M. S., Horcajada, J. P., Hraiech, S., Humbert, L., Iglesias, A. D., Inigo-Campos, A., Jamme, M., Arranz, M. J., Jordan, I., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K. K., Keles, S., Demirkol, Y. K., Klocperk, A., Krol, Z. J., Kuentz, P., Kwan, Y. W. M., Lagier, J. -C., Lau, Y. -L., Le Bourgeois, F., Leo, Y. -S., Lopez, R. L., Leung, D., Levin, M., Levy, M., Levy, R., Li, Z., Linglart, A., Lorenzo-Salazar, J. M., Louapre, C., Lubetzki, C., Luyt, C. -E., Lye, D. C., Mansouri, D., Marjani, M., Pereira, J. M., Martin, A., Pueyo, D. M., Marzana, I., Mathian, A., Matos, L. R. B., Matthews, G. V., Mege, J. -L., Melki, I., Meritet, J. -F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melian, A. M., Martinez, A. M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Munoz-Barrera, A., Nafati, C., Neves, J. F., L. F. P., Ng, Medina, Y. N., Cuadros, E. N., Gonzalo Ocejo-Vinyals, J., Orbak, Z., Oualha, M., Ozcelik, T., Hammarstrom, Q. P., Parizot, C., Pascreau, T., Paz-Artal, E., de Diego, R. P., Philippe, A., Philippota, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A. -S., Reisli, I., Ricart, P., Richard, J. -C., Rivet, N., Riviere, J. G., Blanch, G. R., Rodrigo, C., Rodriguez-Palmero, A., Romero, C. S., Rothenbuhler, A., Rozenberg, F., del Prado, M. Y. R., Riera, J. S., Sanchez, O., Sanchez-Ramon, S., Schluter, A., Schmidt, M., Schweitzer, C. E., Scolari, F., Sediva, A., Seijo, L. M., Sene, D., Senoglu, S., Seppanen, M. R. J., Ilovich, A. S., Shahrooei, M., Smadja, D., Sobh, A., Moreno, X. S., Sole-Violan, J., Soler, C., Soler-Palacin, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiottea, Y., Taupin, J. -L., Tavernier, S. J., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J. T., Trouillet-Assanta, S., Troya, J., Tucci, A., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., van Den Rym, A. M., Vandernoot, I., Vatansev, H., Velez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M. E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B. E., Yucel, F., Zannad, F., Zatz, M., Belota, A., Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M. G., Cazzaniga, M., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abela, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'Ortenzio, E., da Silveira, C., Debray, M. -P., Deplanque, D., Descamps, D., Desvallees, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Eloy, P., Enouf, V. V. E., Esperou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouenan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F. -X., Levy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J. C., Malvy, D., Mambert, M., Mentre, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puechal, O., Rosa-Calatrava, M., Rossignol, B., Roy, C., Schneider, M., Semaille, C., Mohammed, N. S., Tagherset, L., Tardivon, C., Tellier, M. -C., Teoule, F., Terrier, O., Timsit, J. -F., Treoux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Abelc, L., Alcover, A., Aschard, H., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Demangel, C., Deriano, L., Santo, J. D., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hercberg, S., Lantz, O., Patin, E., Pellegrini, S., Pol, S., Rausell, A., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M. -N., Albert, M. L., Alavoine, L., Amat, K. K. A., Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J. -L., Enouf, V., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Lucet, J. -C., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A. G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H. J., Bomers, M., Bos, L., Botta, M., de Brabander, J., Bree, G., Brouwer, M. C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M. P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S. M., Heunks, L., Hollmann, M. W., Horn, J., Hovius, J. W., de Jong, M. D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J. M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M. J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C. S., Stilma, W., Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, A. P. J., de Vries, H., van Vugt, M., Joost Wiersinga, W., Wouters, D., Zwinderman, A. H., Abelb, L., Muhsen, S. A., Al-Mulla, F., Anderson, M. S., Bogunovic, D., Bondarenko, A., Bryceson, Y., Bustamante, C. D., Butte, M., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M. A., Derisi, J. L., Desai, M., Drolet, B. A., Espinosa, S., Franco, J. L., Gregersen, P. K., Hagin, D., Heath, J., Henrickson, S. E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisanda, K., C. -L., Ku, Ling, Y., Lucas, C. L., Maniatis, T., Marodi, L., Milner, J. D., Mironska, K., Morio, T., Notarangeloa, L. D., Novelli, G., Novelli, A., O'Farrelly, C., Okada, S., Planas, A. M., Prando, C., Pujol, A., Renia, L., Renieri, A., Sancho-Shimizu, V., Sankaran, V., Barrett, K. S., Snow, A., Tangye, S., Turvey, S., Uddin, F., Uddin, M. J., Vazquez, S. E., von Bernuth, H., Washington, N., Zawadzki, P., Sua, H. C., Casanovaa, J. -L., Bastard, Paul, Rosen, Lindsey B, Zhang, Qian, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Zhang, Yu, Dorgham, Karim, Philippot, Quentin, Rosain, Jérémie, Béziat, Vivien, Manry, Jérémy, Shaw, Elana, Haljasmägi, Lii, Peterson, Pärt, Lorenzo, Lazaro, Bizien, Lucy, Trouillet-Assant, Sophie, Dobbs, Kerry, de Jesus, Adriana Almeida, Belot, Alexandre, Kallaste, Anne, Catherinot, Emilie, Tandjaoui-Lambiotte, Yacine, Le Pen, Jeremie, Kerner, Gaspard, Bigio, Benedetta, Seeleuthner, Yoann, Yang, Rui, Bolze, Alexandre, Spaan, András N, Delmonte, Ottavia M, Abers, Michael S, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Piemonti, Lorenzo, Ciceri, Fabio, Bilguvar, Kaya, Lifton, Richard P, Vasse, Marc, Smadja, David M, Migaud, Mélanie, Hadjadj, Jérome, Terrier, Benjamin, Duffy, Darragh, Quintana-Murci, Llui, van de Beek, Diederik, Roussel, Lucie, Vinh, Donald C, Tangye, Stuart G, Haerynck, Filomeen, Dalmau, David, Martinez-Picado, Javier, Brodin, Petter, Nussenzweig, Michel C, Boisson-Dupuis, Stéphanie, Rodríguez-Gallego, Carlo, Vogt, Guillaume, Mogensen, Trine H, Oler, Andrew J, Gu, Jingwen, Burbelo, Peter D, Cohen, Jeffrey, Biondi, Andrea, Bettini, Laura Rachele, D'Angio, Mariella, Bonfanti, Paolo, Rossignol, Patrick, Mayaux, Julien, Rieux-Laucat, Frédéric, Husebye, Eystein S, Fusco, Francesca, Ursini, Matilde Valeria, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Rossi, Camillo, Castagnoli, Riccardo, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Duval, Xavier, Ghosn, Jade, Tsang, John S, Goldbach-Mansky, Raphaela, Kisand, Kai, Lionakis, Michail S, Puel, Anne, Zhang, Shen-Ying, Holland, Steven M, Gorochov, Guy, Jouanguy, Emmanuelle, Rice, Charles M, Cobat, Aurélie, Notarangelo, Luigi D, Abel, Laurent, Su, Helen C, Casanova, Jean-Laurent, Meyts, Isabelle, Bastard, P, Rosen, L, Zhang, Q, Michailidis, E, Hoffmann, H, Zhang, Y, Dorgham, K, Philippot, Q, Rosain, J, Beziat, V, Manry, J, Shaw, E, Haljasmagi, L, Peterson, P, Lorenzo, L, Bizien, L, Trouillet-Assant, S, Dobbs, K, de Jesus, A, Belot, A, Kallaste, A, Catherinot, E, Tandjaoui-Lambiotte, Y, Le Pen, J, Kerner, G, Bigio, B, Seeleuthner, Y, Yang, R, Bolze, A, Spaan, A, Delmonte, O, Abers, M, Aiuti, A, Casari, G, Lampasona, V, Piemonti, L, Ciceri, F, Bilguvar, K, Lifton, R, Vasse, M, Smadja, D, Migaud, M, Hadjadj, J, Terrier, B, Duffy, D, Quintana-Murci, L, van de Beek, D, Roussel, L, Vinh, D, Tangye, S, Haerynck, F, Dalmau, D, Martinez-Picado, J, Brodin, P, Nussenzweig, M, Boisson-Dupuis, S, Rodriguez-Gallego, C, Vogt, G, Mogensen, T, Oler, A, Gu, J, Burbelo, P, Cohen, J, Biondi, A, Bettini, L, Dangio, M, Bonfanti, P, Rossignol, P, Mayaux, J, Rieux-Laucat, F, Husebye, E, Fusco, F, Ursini, M, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Castagnoli, R, Montagna, D, Licari, A, Marseglia, G, Duval, X, Ghosn, J, Tsang, J, Goldbach-Mansky, R, Kisand, K, Lionakis, M, Puel, A, Zhang, S, Holland, S, Gorochov, G, Jouanguy, E, Rice, C, Cobat, A, Notarangelo, L, Abel, L, Su, H, Casanova, J, Arias, A, Boisson, B, Boucherit, S, Bustamante, J, Chbihi, M, Chen, J, Chrabieh, M, Kochetkov, T, Le Voyer, T, Liu, D, Nemirovskaya, Y, Ogishi, M, Papandrea, D, Patissier, C, Rapaport, F, Roynard, M, Vladikine, N, Woollett, M, Zhang, P, Kashyap, A, Ding, L, Bosticardo, M, Wang, Q, Ochoa, S, Liu, H, Chauvin, S, Stack, M, Koroleva, G, Bansal, N, Dalgard, C, Snow, A, Abad, J, Aguilera-Albesa, S, Akcan, O, Darazam, I, Aldave, J, Ramos, M, Nadji, S, Alkan, G, Allardet-Servent, J, Allende, L, Alsina, L, Alyanakian, M, Amador-Borrero, B, Amoura, Z, Antoli, A, Arslan, S, Assant, S, Auguet, T, Azot, A, Bajolle, F, Baldolli, A, Ballester, M, Feldman, H, Barrou, B, Beurton, A, Bilbao, A, Blanchard-Rohner, G, Blanco, I, Blandinieres, A, Blazquez-Gamero, D, Bloomfield, M, Bolivar-Prados, M, Borie, R, Bousfiha, A, Bouvattier, C, Boyarchuk, O, Bueno, M, Agra, J, Calimli, S, Capra, R, Carrabba, M, Casasnovas, C, Caseris, M, Castelle, M, Castelli, F, de Vera, M, Castro, M, Chalumeau, M, Charbit, B, Cheng, M, Clave, P, Clotet, B, Codina, A, Colkesen, F, Colobran, R, Comarmond, C, Corsico, A, Darley, D, Dauby, N, Dauger, S, de Pontual, L, Dehban, A, Delplancq, G, Demoule, A, Di Sabatino, A, Diehl, J, Dobbelaere, S, Durand, S, Eldars, W, Elgamal, M, Elnagdy, M, Emiroglu, M, Erdeniz, E, Aytekin, S, Euvrard, R, Evcen, R, Fabio, G, Faivre, L, Falck, A, Fartoukh, M, Faure, M, Arquero, M, Flores, C, Francois, B, Fumado, V, Solis, B, Gaussem, P, Gil-Herrera, J, Gilardin, L, Alarcon, M, Girona-Alarcon, M, Goffard, J, Gok, F, Gonzalez-Montelongo, R, Guerder, A, Gul, Y, Guner, S, Gut, M, Halwani, R, Hammarstrom, L, Hatipoglu, N, Hernandez-Brito, E, Holanda-Pena, M, Horcajada, J, Hraiech, S, Humbert, L, Iglesias, A, Inigo-Campos, A, Jamme, M, Arranz, M, Jordan, I, Kanat, F, Kapakli, H, Kara, I, Karbuz, A, Yasar, K, Keles, S, Demirkol, Y, Klocperk, A, Krol, Z, Kuentz, P, Kwan, Y, Lagier, J, Lau, Y, Le Bourgeois, F, Leo, Y, Lopez, R, Leung, D, Levin, M, Levy, M, Levy, R, Li, Z, Linglart, A, Lorenzo-Salazar, J, Louapre, C, Lubetzki, C, Luyt, C, Lye, D, Mansouri, D, Marjani, M, Pereira, J, Martin, A, Pueyo, D, Marzana, I, Mathian, A, Matos, L, Matthews, G, Mege, J, Melki, I, Meritet, J, Metin, O, Meyts, I, Mezidi, M, Migeotte, I, Millereux, M, Mirault, T, Mircher, C, Mirsaeidi, M, Melian, A, Martinez, A, Morange, P, Mordacq, C, Morelle, G, Mouly, S, Munoz-Barrera, A, Nafati, C, Neves, J, Ng, L, Medina, Y, Cuadros, E, Gonzalo Ocejo-Vinyals, J, Orbak, Z, Oualha, M, Ozcelik, T, Hammarstrom, Q, Parizot, C, Pascreau, T, Paz-Artal, E, de Diego, R, Philippe, A, Philippota, Q, Planas-Serra, L, Ploin, D, Poissy, J, Poncelet, G, Pouletty, M, Quentric, P, Raoult, D, Rebillat, A, Reisli, I, Ricart, P, Richard, J, Rivet, N, Riviere, J, Blanch, G, Rodrigo, C, Rodriguez-Palmero, A, Romero, C, Rothenbuhler, A, Rozenberg, F, del Prado, M, Riera, J, Sanchez, O, Sanchez-Ramon, S, Schluter, A, Schmidt, M, Schweitzer, C, Scolari, F, Sediva, A, Seijo, L, Sene, D, Senoglu, S, Seppanen, M, Ilovich, A, Shahrooei, M, Sobh, A, Moreno, X, Sole-Violan, J, Soler, C, Soler-Palacin, P, Stepanovskiy, Y, Stoclin, A, Taccone, F, Tandjaoui-Lambiottea, Y, Taupin, J, Tavernier, S, Thumerelle, C, Tomasoni, G, Toubiana, J, Alvarez, J, Trouillet-Assanta, S, Troya, J, Tucci, A, Uzunhan, Y, Vabres, P, Valencia-Ramos, J, van Den Rym, A, Vandernoot, I, Vatansev, H, Velez-Santamaria, V, Viel, S, Vilain, C, Vilaire, M, Vincent, A, Voiriot, G, Vuotto, F, Yosunkaya, A, Young, B, Yucel, F, Zannad, F, Zatz, M, Belota, A, Foti, G, Bellani, G, Citerio, G, Contro, E, Pesci, A, Valsecchi, M, Cazzaniga, M, Bole-Feysot, C, Lyonnet, S, Masson, C, Nitschke, P, Pouliet, A, Schmitt, Y, Tores, F, Zarhrate, M, Abela, L, Andrejak, C, Angoulvant, F, Bachelet, D, Basmaci, R, Behillil, S, Beluze, M, Benkerrou, D, Bhavsar, K, Bompart, F, Bouadma, L, Bouscambert, M, Caralp, M, Cervantes-Gonzalez, M, Chair, A, Coelho, A, Couffignal, C, Couffin-Cadiergues, S, D'Ortenzio, E, da Silveira, C, Debray, M, Deplanque, D, Descamps, D, Desvallees, M, Diallo, A, Diouf, A, Dorival, C, Dubos, F, Eloy, P, Enouf, V, Esperou, H, Esposito-Farese, M, Etienne, M, Ettalhaoui, N, Gault, N, Gaymard, A, Gigante, T, Gorenne, I, Guedj, J, Hoctin, A, Hoffmann, I, Jaafoura, S, Kafif, O, Kaguelidou, F, Kali, S, Khalil, A, Khan, C, Laouenan, C, Laribi, S, Le, M, Le Hingrat, Q, Le Mestre, S, Le Nagard, H, Lescure, F, Levy, Y, Levy-Marchal, C, Lina, B, Lingas, G, Lucet, J, Malvy, D, Mambert, M, Mentre, F, Mercier, N, Meziane, A, Mouquet, H, Mullaert, J, Neant, N, Noret, M, Pages, J, Papadopoulos, A, Paul, C, Peiffer-Smadja, N, Petrov-Sanchez, V, Peytavin, G, Picone, O, Puechal, O, Rosa-Calatrava, M, Rossignol, B, Roy, C, Schneider, M, Semaille, C, Mohammed, N, Tagherset, L, Tardivon, C, Tellier, M, Teoule, F, Terrier, O, Timsit, J, Treoux, T, Tual, C, Tubiana, S, van der Werf, S, Vanel, N, Veislinger, A, Visseaux, B, Wiedemann, A, Yazdanpanah, Y, Abelc, L, Alcover, A, Aschard, H, Astrom, K, Bousso, P, Bruhns, P, Cumano, A, Demangel, C, Deriano, L, Santo, J, Dromer, F, Eberl, G, Enninga, J, Fellay, J, Gomperts-Boneca, I, Hasan, M, Hercberg, S, Lantz, O, Patin, E, Pellegrini, S, Pol, S, Rausell, A, Rogge, L, Sakuntabhai, A, Schwartz, O, Schwikowski, B, Shorte, S, Tangy, F, Toubert, A, Touvier, M, Ungeheuer, M, Albert, M, Alavoine, L, Amat, K, Bielicki, J, Bruijning, P, Burdet, C, Caumes, E, Charpentier, C, Coignard, B, Costa, Y, Damond, F, Dechanet, A, Delmas, C, Ecobichon, J, Frezouls, W, Houhou, N, Ilic-Habensus, E, Kikoine, J, Lebeaux, D, Leclercq, A, Lehacaut, J, Letrou, S, Manchon, P, Mandic, M, Meghadecha, M, Motiejunaite, J, Nouroudine, M, Piquard, V, Postolache, A, Quintin, C, Rexach, J, Roufai, L, Terzian, Z, Thy, M, Vignali, V, van Agtmael, M, Algera, A, van Baarle, F, Bax, D, Beudel, M, Bogaard, H, Bomers, M, Bos, L, Botta, M, de Brabander, J, Bree, G, Brouwer, M, de Bruin, S, Bugiani, M, Bulle, E, Chouchane, O, Cloherty, A, Elbers, P, Fleuren, L, Geerlings, S, Geerts, B, Geijtenbeek, T, Girbes, A, Goorhuis, B, Grobusch, M, Hafkamp, F, Hagens, L, Hamann, J, Harris, V, Hemke, R, Hermans, S, Heunks, L, Hollmann, M, Horn, J, Hovius, J, de Jong, M, Koning, R, van Mourik, N, Nellen, J, Paulus, F, Peters, E, van der Poll, T, Preckel, B, Prins, J, Raasveld, J, Reijnders, T, Schinkel, M, Schultz, M, Schuurman, A, Sigaloff, K, Smit, M, Stijnis, C, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A, van der Valk, M, Veelo, D, Vlaar, A, de Vries, H, van Vugt, M, Joost Wiersinga, W, Wouters, D, Zwinderman, A, Abelb, L, Iuti, F, Muhsen, S, Al-Mulla, F, Anderson, M, Bogunovic, D, Bondarenko, A, Bryceson, Y, Bustamante, C, Butte, M, Chakravorty, S, Christodoulou, J, Cirulli, E, Condino-Neto, A, Cooper, M, Derisi, J, Desai, M, Drolet, B, Espinosa, S, Franco, J, Gregersen, P, Hagin, D, Heath, J, Henrickson, S, Hsieh, E, Imai, K, Itan, Y, Karamitros, T, Kisanda, K, Ku, C, Ling, Y, Lucas, C, Maniatis, T, Marodi, L, Milner, J, Mironska, K, Morio, T, Notarangeloa, L, Novelli, G, Novelli, A, O'Farrelly, C, Okada, S, Planas, A, Prando, C, Pujol, A, Renia, L, Renieri, A, Sancho-Shimizu, V, Sankaran, V, Barrett, K, Turvey, S, Uddin, F, Uddin, M, Vazquez, S, von Bernuth, H, Washington, N, Zawadzki, P, Sua, H, Casanovaa, J, Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Rockefeller University [New York], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Tartu, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Lyon Immunopathology Federation (LIFe), Tartu University Hospital [Tartu, Estonia], Hôpital Foch [Suresnes], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Helix [San Mateo, CA], University Medical Center [Utrecht], IRCCS Ospedale San Raffaele [Milan, Italy], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Yale University School of Medicine, Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Paris (UP), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], McGill University Health Center [Montreal] (MUHC), Garvan Institute of Medical Research [Darlinghurst, Australia], University of New South Wales [Sydney] (UNSW), Ghent University Hospital, Hospital Universitario Mutua de Terrassa, Universitat de Barcelona (UB), Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute (IGTP), Universitat de Vic-Universitat Central de Catalunya, España, Institució Catalana de Recerca i Estudis Avançats (ICREA), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Hospital Universitario de Gran Canaria Dr Negrin, University Fernando Pessoa - UFP, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Aarhus University Hospital, Aarhus University [Aarhus], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Fondazione MBBM-Ospedale [Monza, Italie], San Gerardo Hospital, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bergen (UiB), Haukeland University Hospital, Consiglio Nazionale delle Ricerche [Napoli] (CNR), Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Brescia [Brescia], Università degli Studi di Pavia, Fondazione IRCCS Policlinico San Matteo, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Paris - UFR Médecine Paris Nord [Santé] (UP Médecine Paris Nord), Service d'Immunologie [CHU Pitié-Salpétrière], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), UM1 HG006504/HG/NHGRI NIH HHS/United States, P01 AI138938/AI/NIAID NIH HHS/United States, U19 AI111825/AI/NIAID NIH HHS/United States, U24 HG008956/HG/NHGRI NIH HHS/United States, MR/S032304/1/MRC_/Medical Research Council/United Kingdom, UKRI Future Leader's Fellowship, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANRS-COV05), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, the Institut Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. Samples from San Raffaele Hospital were obtained through the Covid-BioB project and by healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical laboratory and clinical research unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort Study Group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Milieu Intérieur Consortium was supported by the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Milieu Intérieur grant (ANR-10-LABX-69-01) (primary investigators: L.Q.-M. and D.Du.). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant 'DIGITAL COVID' (primary investigator: G.G.). S.G.T. is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia and a COVID19 Rapid Response Grant awarded by UNSW Sydney. C.R.-G. and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation RTC-2017-6471-1, AEI/FEDER, UE) and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). S.T.-A. and A.B. were supported by ANR-20-COVI-0064 (primary investigator: A.Be.). This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013,' by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and by a public grant overseen by the French National Research Agency (ANR) as part of the second Investissements d’Avenir program FIGHT-HF (reference no. ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence' (reference no. ANR-15-IDEX-04-LUE) (45), and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology, by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to F.R.-L.), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants from the Amsterdam Corona Research Fund, the Dr. C.J. Vaillant Fund, and the Netherlands Organization for Health Research and Development [ZonMw, NWO-Vici-Grant (grant no. 918·19·627 to D.v.d.B.)]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e comorbidita'). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. J.H. holds an Institut Imagine M.D.-Ph.D. fellowship from the Fondation Bettencourt Schueller. J.R. is supported by the INSERM Ph.D. program ('poste d’accueil Inserm'). P.Ba. was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the M.D.-Ph.D. program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association 'Turner et vous' for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K.K. was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (contract no. HHSN316201300006W/HHSN27200002 to MSC, Inc.), the Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data, and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support. Biomedical Advanced Research and Development Authority was supported under contract no. HHSO10201600031C (to J.H.). Financial support was provided by the National Institute of Allergy and Infectious Diseases (NIAID) K08AI135091, the Burroughs Wellcome Fund CAMS, the Clinical Immunology Society, and the American Academy of Allergy, Asthma, and Immunology, We thank the patients, their families, and healthy donors for placing their trust in us. We thank the French Incontinentia pigmenti association for their help and support. We thank Y. Nemirovskaya, D. Papandrea, M. Woollett, D. Liu, C. Rivalain, and C. Patissier for administrative assistance, D. Kapogiannis (National Institute on Aging) for providing healthy donor samples, and S. Xirasager, J. Barnett, X. Cheng, S. Weber, J. Danielson, B. Garabedian, and H. Matthews for their assistance in this study. We also thank R. Apps, B. Ryan, and Y. Belkaid of the CHI for their assistance. We thank the CRB-Institut Jérôme Lejeune, CRB-BioJeL, Paris, France, for their assistance. We thank M. C. García Guerrero, I. Erkizia, E. Grau, M. Massanella from IrsiCaixa AIDS Research Institute, Badalona, Spain, and J. Guitart from the Department of Clinical Genetics, University Hospital Germans Trias i Pujol, Badalona, Spain, for providing samples. We also thank J. Dalmau from IrsiCaixa for assistance, HGID Lab, NIAID-USUHS Immune Response to COVID Group, COVID Clinicians, COVID-STORM Clinicians, Imagine COVID Group, French COVID Cohort Study Group, The Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic, CoV-Contact Cohort: Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, Hélène Espérou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, Valérie Vignali, Benoit Visseaux, Yazdan Yazdanpanah, COVID Human Genetic Effort: Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, Andrés Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O'Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-Palacín, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova, Amsterdam UMC Covid-19 Biobank: Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P. J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek, HGID Lab: Andrés Augusto Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang, NIAID-USUHS Immune Response to COVID Group: Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow, COVID Clinicians: Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, Aurélie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan José Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Colkesen, Roger Colobran, Cloé Comarmond, Angelo G. Corsico, David Dalmau, David Ross Darley, Nicolas Dauby, Stéphane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria Fumadó, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mónica Girona-Alarcón, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Iolanda Jordan, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. Król, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Agnes Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, Clémence Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz-Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelik, Qiang Pan Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, Agustí Rodríguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-Ramón, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé-Violán, Catherine Soler, Pere Soler-Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hulya Vatansev, Valentina Vélez-Santamaria, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot, COVID-STORM Clinicians: Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Imagine COVID Group: Christine Bole-Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate, French COVID Cohort Study Group: Laurent Abel, Claire Andrejak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadiergues, Eric D’ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent V. E. Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Yves Lévy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadj, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanan, The Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluis Quintana-Murci, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-20-COVI-0064,IFN-COVID19,Etude de la régulation de la réponse interferon de type I dans le control de l'infection par SARS-Cov2 et sa pathogènese(2020), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), Howard Hughes Medical Institute, Rockefeller University, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondazione Telethon, Ministère des Solidarités et de la Santé (France), European Commission, National Health and Medical Research Council (Australia), University of New South Wales (Australia), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Rosen, Lindsey B., Michailidis, Eleftherios, Haljasmägi, Liis, Spaan, András N., Quintana-Murci, Lluis, Beek, Diederik van der, Vinh, Donald C., Tangye, Stuart G., Martínez-Picado, Javier, Brodin, Peter, Nussenzweig, Michel C., Rodríguez-Gallego, Carlos, Mogensen, Trine, Oler, Andrew J., Burbelo, Peter D., Husebye, Eystein S., Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, ACS - Microcirculation, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Yale School of Medicine [New Haven, Connecticut] (YSM), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Garvan Institute of medical research, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), San Gerardo Hospital of Monza, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Pavia = University of Pavia (UNIPV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and J. Guitart from the Department of Clinical Genetics, University Hospital Germans Trias i Pujol, Badalona, Spain, for providing samples. We also thank J. Dalmau from IrsiCaixa for assistance HGID Lab, NIAID-USUHS Immune Response to COVID Group, COVID Clinicians, COVID-STORM Clinicians, Imagine COVID Group, French COVID Cohort Study Group, The Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic CoV-Contact Cohort: Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, Hélène Espérou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, Valérie Vignali, Benoit Visseaux, Yazdan Yazdanpanah COVID Human Genetic Effort: Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, Andrés Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O'Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-Palacín, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova Amsterdam UMC Covid-19 Biobank: Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P. J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek HGID Lab: Andrés Augusto Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang NIAID-USUHS Immune Response to COVID Group: Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow COVID Clinicians: Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, Aurélie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan José Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Colkesen, Roger Colobran, Cloé Comarmond, Angelo G. Corsico, David Dalmau, David Ross Darley, Nicolas Dauby, Stéphane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria Fumadó, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mónica Girona-Alarcón, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Iolanda Jordan, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. Król, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Agnes Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, Clémence Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz-Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelik, Qiang Pan Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, Agustí Rodríguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-Ramón, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé-Violán, Catherine Soler, Pere Soler-Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hulya Vatansev, Valentina Vélez-Santamaria, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot COVID-STORM Clinicians: Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga Imagine COVID Group: Christine Bole-Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate French COVID Cohort Study Group: Laurent Abel, Claire Andrejak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadiergues, Eric D’ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent V. E. Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Yves Lévy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadj, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanan The Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluis Quintana-Murci, Bastard, Paul [0000-0002-5926-8437], Rosen, Lindsey B. [0000-0001-5894-3878], Zhang, Qian [0000-0002-9040-3289], Michailidis, Eleftherios [0000-0002-9907-4346], Dorgham, Karim [0000-0001-9539-3203], Béziat, Vivien [0000-0002-4020-824X], Manry, Jérémy [0000-0001-5998-2051], Shaw, Elana [0000-0001-9265-8026], Haljasmägi, Liis [0000-0001-7162-9808], Peterson, Pärt [0000-0001-6755-791X], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Trouillet-Assant, Sophie [0000-0001-6439-4705], Dobbs, Kerry [0000-0002-3432-3137], Belot, Alexandre [0000-0003-4902-5332], Kallaste, Anne [0000-0002-7492-667X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Le Pen, Jeremie [0000-0001-7025-9526], Kerner, Gaspard [0000-0003-0146-9428], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Bolze, Alexandre [0000-0001-7399-2766], Spaan, András N. [0000-0001-5981-7259], Aiuti, Alessandro [0000-0002-5398-1717], Lampasona, Vito [0000-0001-5162-8445], Piemonti, Lorenzo [0000-0002-2172-2198], Bilguvar, Kaya [0000-0002-7313-7652], Migaud, Mélanie [0000-0003-3062-1214], Hadjadj, Jérome [0000-0002-2520-3272], Terrier, Benjamin [0000-0001-6612-7336], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Beek, Diederik van der [0000-0002-4571-044X], Roussel, Lucie [0000-0001-5355-702X], Vinh, Donald C. [0000-0003-1347-7767], Tangye, Stuart G. [0000-0002-5360-5180], Dalmau, David [0000-0003-1936-478X], Martínez-Picado, Javier [0000-0002-4916-2129], Brodin, Peter [0000-0002-8103-0046], Nussenzweig, Michel C. [0000-0003-0592-8564], Boisson-Dupuis, Stéphanie [0000-0002-7115-116X], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Mogensen, Trine [0000-0002-1853-9704], Oler, Andrew J. [0000-0002-6310-0434], Burbelo, Peter D. [0000-0003-1717-048X], Cohen, Jeffrey [0000-0003-0238-7176], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Rieux-Laucat, Frédéric [0000-0001-7858-7866], Husebye, Eystein S. [0000-0002-7886-2976], Castagnoli, Riccardo [0000-0003-0029-9383], Licari, Amelia [0000-0002-1773-6482], Vougny, Marie-Christine, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, Etude de la régulation de la réponse interferon de type I dans le control de l'infection par SARS-Cov2 et sa pathogènese - - IFN-COVID192020 - ANR-20-COVI-0064 - COVID-19 - VALID, Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé - - AIROCovid192020 - ANR-20-COVI-0022 - COVID-19 - VALID, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anesthésiologie et soins intensifs [CHU Pitié-Salpêtrière], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Paris Diderot - Paris 7 - UFR Lettres, Arts, Langues, Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service d'immunologie [CHU Pitié-Salpétrière], Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The 'Milieu Intérieur' cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence 'Milieu Intérieur' Grant (ANR-10-LABX-69-01) (PI: L Quintana-Murci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant 'DIGITAL COVID' (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1, AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013', by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence', reference ANR-15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw, NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e comorbidita'). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program ('poste d’accueil Inserm'). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association 'Turner et vous' for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support., The Milieu Intérieur Consortium : Laurent Abel 1, Andres Alcover 2, Hugues Aschard 2, Kalla Astrom 3, Philippe Bousso 2, Pierre Bruhns 2, Ana Cumano 2, Caroline Demangel 2, Ludovic Deriano 2, James Di Santo 2, Françoise Dromer 2, Gérard Eberl 2, Jost Enninga 2, Jacques Fellay 4, Ivo Gomperts-Boneca 2, Milena Hasan 2, Serge Hercberg 5, Olivier Lantz 6, Hugo Mouquet 2, Etienne Patin 2, Sandra Pellegrini 2, Stanislas Pol 7, Antonio Rausell 8, Lars Rogge 2, Anavaj Sakuntabhai 2, Olivier Schwartz 2, Benno Schwikowski 2, Spencer Shorte 2, Frédéric Tangy 2, Antoine Toubert 9, Mathilde Touvier 10, Marie-Noëlle Ungeheuer 2, Matthew L. Albert 11*, Darragh Duffy 2*, Lluis Quintana-Murci 2* - 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine, Paris, France. 9Hôpital Saint-Louis, Paris, France. 10Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Bobigny, France. 11In Sitro, San Francisco, CA, USA. *Co-coordinators of The Milieu Intérieur Consortium. Additional information can be found at: www.milieuinterieur.fr/en., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC, Netherlands Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua D. Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa F. P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Dasman Diabetes Institute, Department of Genetics and Bioinformatics, Dasman, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Department, Faculty of Medicine and Pharmacy, Averroes University Hospital, LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Department of Pediatrics and Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco, Chan Zuckerberg Biohub, San Francisco, CA, USA. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Department of Biomedicine and Prevention, University of Rome 'Tor Vergata,' Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL - Hospital Duran I Reynals, Catalan Institution for Research and Advanced Studies (ICREA), CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63Medical Genetics, University of Siena, Italy, Genetica Medica, Azienda Ospedaliero-Universitaria Senese, GEN-COVID Multicenter Study, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Laboratory, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College, Centre for Precision Therapeutics, NeuroGen Children's Healthcare, Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, United Arab Emirates, The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 75Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, USA. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80The Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., ANR-10-LABX-0062,IBEID,Biologie Intégrative des Maladies Infectieuses Emergentes(2011), ANR-10-LABX-0020,NUMEV,Digital and Hardware Solutions and Modeling for the Environement and Life Sciences(2010), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Pulmonary medicine, Medical Microbiology and Infection Prevention, Internal medicine, Intensive care medicine, APH - Quality of Care, and Özçelik, Tayfun
- Subjects
Male ,COVID19 ,Immunoglobulin G ,DISEASE ,MESH: Antibodies, Neutralizing ,0302 clinical medicine ,MESH: Interferon alpha-2 ,80 and over ,Medicine ,Asymptomatic Infections ,MESH: Immunoglobulin G ,Aged, 80 and over ,0303 health sciences ,MESH: Middle Aged ,COVID Clinicians ,MESH: Case-Control Studies ,3. Good health ,Settore MED/03 ,030220 oncology & carcinogenesis ,MESH: Critical Illness ,Interferon Type I ,Science & Technology - Other Topics ,Viral disease ,MESH: Pandemics ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Critical Illness ,Immunology ,Pneumonia, Viral ,Interferon alpha-2 ,HGID Lab ,03 medical and health sciences ,Betacoronavirus ,Genetics ,Humans ,MESH: SARS-CoV-2 ,COVID Human Genetic Effort ,Aged ,Autoantibodies ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,Science & Technology ,CYTOKINES ,MESH: Adult ,Pneumonia ,medicine.disease ,Antibodies, Neutralizing ,COVID-STORM Clinicians ,MESH: Pneumonia, Viral ,Case-Control Studies ,NIAID-USUHS Immune Response to COVID Group ,MESH: Female ,MESH: Interferon Type I ,MESH: Coronavirus Infections ,CHRONIC MUCOCUTANEOUS CANDIDIASIS ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,medicine.disease_cause ,Autoimmunity ,CoV-Contact Cohort ,MESH: Aged, 80 and over ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Medicine and Health Sciences ,MESH: Autoantibodies ,MESH: COVID-19 ,Online ,Viral ,Chronic mucocutaneous candidiasis ,Imagine COVID Group ,Amsterdam UMC Covid-19 Biobank ,Neutralizing ,Research Articles ,MESH: Aged ,Multidisciplinary ,biology ,Middle Aged ,Multidisciplinary Sciences ,Milieu Intérieur Consortium ,MESH: Betacoronavirus ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,medicine.symptom ,Coronavirus Infections ,Research Article ,Sciences exactes et naturelles ,Adult ,INTERFERON ,General Science & Technology ,PROTEINS ,French COVID Cohort Study Group ,MESH: Asymptomatic Infections ,COVID-19 ,Pandemics ,SARS-CoV-2 ,Asymptomatic ,Antibodies ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,030304 developmental biology ,Phenocopy ,business.industry ,R-Articles ,Autoantibody ,GAMMA ,MESH: Male ,3121 General medicine, internal medicine and other clinical medicine ,ANTIBODIES ,biology.protein ,3111 Biomedicine ,business - Abstract
HGID Lab Andrés Augusto Arias1,3, Bertrand Boisson1,2, Soraya Boucherit2, Jacinta Bustamante1,2, Marwa Chbihi2, Jie Chen1, Maya Chrabieh2, Tatiana Kochetkov1, Tom Le Voyer2, Dana Liu1, Yelena Nemirovskaya1, Masato Ogishi1, Dominick Papandrea1, Cécile Patissier2, Franck Rapaport1, Manon Roynard2, Natasha Vladikine2, Mark Woollett1, Peng Zhang1 1St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University. 2Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children. 3School of Microbiology and Group of Primary Immunodeficiencies, University of Antioquia UdeA, Medellin, Colombia., NIAID-USUHS Immune Response to COVID Group Anuj Kashyap1, Li Ding1, Marita Bosticardo1, Qinlu Wang2, Sebastian Ochoa1, Hui Liu1, Samuel D. Chauvin3, Michael Stack1, Galina Koroleva4, Neha Bansal5, Clifton L. Dalgard6,7, Andrew L. Snow8 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2Bioinformatics and Computational Biosciences Branch, NIAID Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 3Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 4NIH Center for Human Immunology, NIH, Bethesda, MD, USA. 5Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA. 6PRIMER, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 7Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 8Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Ahmed A. Bousfiha33, Claire Bouvattier34, Oksana Boyarchuk35, Maria Rita P. Bueno36, Jacinta Bustamante20, Juan José Cáceres Agra37, Semra Camli38, Ruggero Capra39, Maria Carrabba40, Carlos Casasnovas41, Marion Caseris42, Martin Castelle43, Francesco Castelli44, Martín Castillo de Vera45, Mateus V. Castro36, Emilie Catherinot46, Martin Chalumeau47, Bruno Charbit48, Matthew P. Cheng49, Père Clavé31, Bonaventura Clotet50, Anna Codina51, Fatih Colkesen52, Fatma Colkesen53, Roger Colobran 54, Cloé Comarmond55, Angelo G. Corsico56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Antonio Di Sabatino65, Jean-Luc Diehl66, Stephanie Dobbelaere67, Sophie Durand68, Waleed Eldars69, Mohamed Elgamal70, Marwa H. Elnagdy71, Melike Emiroglu72, Emine Hafize Erdeniz73, Selma Erol Aytekin74, Romain Euvrard75, Recep Evcen76, Giovanna Fabio40, Laurence Faivre77, Antonin Falck42, Muriel Fartoukh78, Morgane Faure79, Miguel Fernandez Arquero80, Carlos Flores81, Bruno Francois82, Victoria Fumadó83, Francesca Fusco84, Blanca Garcia Solis85, Pascale Gaussem86, Juana Gil-Herrera87, Laurent Gilardin88, Monica Girona Alarcon89, Mónica Girona-Alarcón89, Jean-Christophe Goffard90, Funda Gok91, Rafaela González-Montelongo92, Antoine Guerder93, Yahya Gul94, Sukru Nail Guner94, Marta Gut95, Jérôme Hadjadj96, Filomeen Haerynck97, Rabih Halwani98, Lennart Hammarström99, Nevin Hatipoglu100, Elisa Hernandez-Brito101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Sami Hraiech104, Linda Humbert105, Alejandro D. Iglesias106, Antonio Íñigo-Campos92, Matthieu Jamme107, María Jesús Arranz108, Iolanda Jordan109, Fikret Kanat110, Hasan Kapakli111, Iskender Kara112, Adem Karbuz113, Kadriye Kart Yasar114, Sevgi Keles115, Yasemin Kendir Demirkol116, Adam Klocperk117, Zbigniew J. Król118, Paul Kuentz119, Yat Wah M. Kwan120, Jean-Christophe Lagier121, Yu-Lung Lau122, Fleur Le Bourgeois60, Yee-Sin Leo123, Rafael Leon Lopez124, Daniel Leung122, Michael Levin125, Michael Levy60, Romain Lévy20, Zhi Li48, Agnes Linglart126, José M. Lorenzo-Salazar92, Céline Louapre127, Catherine Lubetzki127, Charles-Edouard Luyt128, David C. Lye129, Davood Mansouri130, Majid Marjani131, Jesus Marquez Pereira132, Andrea Martin133, David Martínez Pueyo134, Javier Martinez-Picado135, Iciar Marzana136, Alexis Mathian14, Larissa R. B. Matos36, Gail V. Matthews137, Julien Mayaux138, Jean-Louis Mège139, Isabelle Melki140, Jean-François Meritet141, Ozge Metin142, Isabelle Meyts143, Mehdi Mezidi144, Isabelle Migeotte145, Maude Millereux146, Tristan Mirault147, Clotilde Mircher68, Mehdi Mirsaeidi148, Abián Montesdeoca Melián149, Antonio Morales Martinez150, Pierre Morange151, Demence Mordacq105, Guillaume Morelle152, Stéphane Mouly13, Adrián Muñoz-Barrera92, Cyril Nafati153, João Farela Neves154, Lisa F. P. Ng155, Yeray Novoa Medina156, Esmeralda Nuñez Cuadros157, J. Gonzalo Ocejo-Vinyals158, Zerrin Orbak159, Mehdi Oualha20, Tayfun Özçelik160, Qiang Pan Hammarström161, Christophe Parizot138, Tiffany Pascreau162, Estela Paz-Artal163, Sandra Pellegrini48, Rebeca Pérez de Diego85, Aurélien Philippe164, Quentin Philippot78, Laura Planas-Serra165, Dominique Ploin166, Julien Poissy167, Géraldine Poncelet42, Marie Pouletty168, Paul Quentric138, Didier Raoult139, Anne-Sophie Rebillat68, Ismail Reisli169, Pilar Ricart170, Jean-Christophe Richard171, Nadia Rivet28, Jacques G. Rivière172, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego173, Agustí Rodríguez-Palmero174, Carolina Soledad Romero175, Anya Rothenbuhler176, Flore Rozenberg177, Maria Yolanda Ruiz del Prado178, Joan Sabater Riera15, Oliver Sanchez179, Silvia Sánchez-Ramón180, Agatha Schluter165, Matthieu Schmidt181, Cyril E. Schweitzer182, Francesco Scolari183, Anna Sediva184, Luis M. Seijo185, Damien Sene13, Sevtap Senoglu114, Mikko Seppänen186, Alex Serra Ilovich187, Mohammad Shahrooei62, David Smadja188, Ali Sobh189, Xavier Solanich Moreno15, Jordi Solé-Violán190, Catherine Soler191, Pere Soler-Palacín133, Yuri Stepanovskiy192, Annabelle Stoclin193, Fabio Taccone145, Yacine Tandjaoui-Lambiotte194, Jean-Luc Taupin195, Simon J. Tavernier196, Benjamin Terrier197, Caroline Thumerelle105, Gabriele Tomasoni198, Julie Toubiana47, Josep Trenado Alvarez199, Sophie Trouillet-Assant200, Jesús Troya201, Alessandra Tucci202, Matilde Valeria Ursini84, Yurdagul Uzunhan203, Pierre Vabres204, Juan Valencia-Ramos205, Ana Maria Van Den Rym85, Isabelle Vandernoot206, Hulya Vatansev207, Valentina Vélez-Santamaria41, Sébastien Viel166, Cédric Vilain208, Marie E. Vilaire68, Audrey Vincent34, Guillaume Voiriot209, Fanny Vuotto105, Alper Yosunkaya91, Barnaby E. Young123, Fatih Yucel210, Faiez Zannad211, Mayana Zatz36, Alexandre Belot212* 1University Hospital and Research Institute “Germans Trias i Pujol”, Badalona, Spain. 2Navarra Health Service Hospital, Pamplona, Spain. 3Division of Pediatric Infectious Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 4Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru. 6Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat Spain. 7Virology Research Center, National institutes of Tuberculosis and Lung diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8Division of Pediatric Infectious Diseases, Faculty of Medicine, Selcuk University, Konya, Turkey. 9Intensive care unit, Hôpital Européen, Marseille, France. 10Immunology Department, University Hospital 12 de Octubre. Research Institute imas12. Complutense University, Madrid, Spain. 11Hospital Sant Joan de Déu, Barcelona, Spain. 12Department of Biological Immunology, Necker Hospital for Sick Children, APHP and INEM, Paris, France. 13Internal medicine department, Hôpital Lariboisière, APHP; Université de Paris, Paris, France. 14Internal medicine department, Pitié-Salpétrière Hospital, Paris, France. 15Hospital Universitari de Bellvitge, Barcelona, Spain. 16Division of Clinical Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 17Joint Research Unit, Hospices Civils de Lyon-bio Mérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 18Hospital U. de Tarragona Joan XXIII. Universitat Rovira i Virgili (URV). IISPV, Tarragona, Spain. 19Private practice, Paris, France. 20Necker Hospital for Sick Children, AP-HP, Paris, France. 21Department of Infectious Diseases, CHU de Caen, Caen, France. 22Consorcio Hospital General Universitario, Valencia, Spain. 23The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 24Dept Urology, Nephrology, Transplantation, APHP-SU, Sorbonne Université, INSERM U 1082, Paris, France. 25Service de Médecine Intensive–Réanimation et Pneumologie, APHP Hôpital Pitié–Salpêtrière, Paris, France. 26Cruces University Hospital, Bizkaia, Spain. 27Paediatric Immunology and Vaccinology Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. 28Hematology, Georges Pompidou Hospital, APHP, Paris, France. 29Pediatric Infectious Diseases Unit. Instituto de Investigación 12 de Octubre (imas12). Hospital Universitario 12 de Octubre, Madrid, Spain. 30Department of Immunology, Motol University Hospital, 2nd Faculty of Medicine, Charles University, Department of Pediatrics, Thomayer’s Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. 31Centro de Investigación Biomédica en Red de Enfermedades Hepàticas y Digestivas (Ciberehd). Hospital de Mataró, Consorci Sanitari del Maresme, Mataró, Spain. 32Service de Pneumologie, Hopital Bichat, APHP, Paris, France. 33Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 34Endocrinology unit, APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 35Department of Children's Diseases and Pediatric Surgery, I.Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. 36Human Genome and stem-cell research center- University of São Paulo, São Paulo, Brazil. 37Hospital Insular, Las Palmas de Gran Canaria, Spain. 38Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Konya State Hospital, Konya, Turkey. 39MS Center, Spedali Civili, Brescia, Italy. 40Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 41Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. 42Hopital Robert Debré, Paris, France. 43Pediatric Immuno-hematology Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France. 44Department of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 45Doctoral Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 46Hôpital Foch, Suresnes, France. 47Necker Hospital for Sick Children, Paris University, AP-HP, Paris, France. 48Pasteur Institute, Paris, France. 49McGill University Health Centre, Montreal, Canada. 50University Hospital and Research Institute “Germans Trias i Pujol”, IrsiCaixa AIDS Research Institute, UVic-UCC, Badalona, Spain. 51Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Esplugues, Spain. 52Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 53Department of Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey. 54Hospital Universitari Vall d’Hebron, Barcelona, Spain. 55Pitié-Salpêtrière Hospital, Paris, France. 56Respiratory Diseases Division, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy. 57Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 58UNSW Medicine, St Vincent's Clinical School; Department of Thoracic Medicine, St Vincent's Hospital Darlinghurst, Sidney, Australia. 59CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium. 60Pediatric Intensive Care Unit, Robert-Debré University Hospital, APHP, Paris, France. 61Sorbonne Paris Nord, Hôpital Jean Verdier, APHP, Bondy, France. 62Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran. 63Centre de génétique humaine, CHU Besançon, Besançon, France. 64Sorbonne Université médecine and APHP Sorbonne université site Pitié-Salpêtrière, Paris, France. 65Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. 66Intensive Care unit, Georges Pompidou Hospital, APHP, Paris, France. 67Department of Pneumology, AZ Delta, Roeselare, Belgium. 68Institut Jérôme Lejeune, Paris, France. 69Department of Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 70Department of Chest, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 71Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 72Faculty of Medicine, Division of Pediatric Infectious Diseases, Selcuk University, Konya, Turkey. 73Division of Pediatric Infectious Diseases, Ondokuz Mayıs University, Samsun, Turkey. 74Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey. 75Centre Hospitalier Fleyriat, Bourg-en-Bresse, France. 76Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 77Centre de Génétique, CHU Dijon, Dijon, France. 78APHP Tenon Hospital, Paris, France. 79Sorbonne Universités, UPMC University of Paris, Paris, France. 80Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. 81Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain; Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, Spain. 82CHU Limoges and Inserm CIC 1435 & UMR 1092, Limoges, France. 83Infectious Diseases Unit, Department of Pediatrics, Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu, Spain; Universitat de Barcelona (UB), Barcelona, Spain. 84Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, IGB-CNR, Naples, Italy. 85Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 86Hematology, APHP, Hopital Européen Georges Pompidou and Inserm UMR-S1140, Paris, France. 87Hospital General Universitario and Instituto de Investigación Sanitaria "Gregorio Marañón", Madrid, Spain. 88Bégin military Hospital, Bégin, France. 89Pediatric Intensive Care Unit, Hospital Sant Joan de Déu, Barcelona, Spain. 90Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 91Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 92Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain. 93Assistance Publique Hôpitaux de Paris, Paris, France. 94Division of Allergy and Immunology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 95CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST); Universitat Pompeu Fabra (UPF), Barcelona, Spain. 96Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Paris, France. 97Ghent University Hospital, Ghent, Belgium. 98Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 99Department of Biosciences and Nutrition, SE14183, Huddinge, Karolinska Institutet, Stockholm, Sweden. 100Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 101Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 102IntensivenCare Unit. Marqués de Valdecilla Hospital, Santander, Spain. 103Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. 104Intensive care unit, APHM, Marseille, France. 105CHU Lille, Lille, France. 106Department of Pediatrics, Columbia University, New York, NY, USA. 107Centre hospitalier intercommunal Poissy Saint Germain en Laye, Poissy, France. 108Division of Respiratory Diseases, Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 109Hospital Sant Joan de Déu, Kids Corona Platfform, Barcelona, Spain. 110Selcuk University, Faculty of Medicine, Chest Diseases Department, Konya, Turkey. 111Division of Allergy and Immunology, Balikesir Ataturk City Hospital, Balikesir, Turkey. 112Division of Critical Care Medicine, Selcuk University, Faculty of Medicine, Konya, Turkey. 113Division of Pediatric Infectious Diseases, Prof. Dr. Cemil Tascıoglu City Hospital, Istanbul, Turkey. 114Departments of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 115Meram Medical Faculty, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 116Health Sciences University, Umraniye Education and Research Hospital, Istanbul, Turkey. 117Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic. 118Central Clinical Hospital of Ministry of the Interior and Administration in Warsaw, Warsaw, Poland. 119Oncobiologie Génétique Bioinformatique, PC Bio, CHU Besançon, Besançon, France. 120Paediatric Infectious Disease Unit, Hospital Authority Infectious Disease Center, Princess Margaret Hospital, Hong Kong (Special Administrative Region), China. 121Aix Marseille Univ, IRD, MEPHI, IHU Méditerranée Infection, Marseille, France. 122Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China. 123National Centre for Infectious Diseases, Singapore. 124Hospital Universitario Reina Sofía, Cordoba, Spain. 125Imperial College, London, England. 126Endocrinology and diabetes for children, AP-HP, Bicêtre Paris-Saclay hospital, Le Kremlin-Bicêtre, France. 127Neurology unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 128Intensive care unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 129National Centre for Infectious Diseases; Tan Tock Seng Hospital; Yong Loo Lin School of Medicine; Lee Kong Chian School of Medicine, Singapore. 130Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 131Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 132Hospital Sant Joan de Déu and University of Barcelona, Barcelona, Spain. 133Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. 134Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain. 135IrsiCaixa AIDS Research Institute, ICREA, UVic-UCC, Research Institute “Germans Trias i Pujol”, Badalona, Spain. 136Department of Laboratory, Cruces University Hospital, Barakaldo, Bizkaia, Spain. 137University of New South Wales, Australia. 138APHP Pitié-Salpêtrière Hospital, Paris, France. 139Aix-Marseille University, APHM, Marseille, France. 140Robert Debré Hospital, Paris, France. 141APHP Cohin Hospital, Paris, France. 142Necmettin Erbakan University Meram Faculty of Medicine Department of Pediatric Infectious Diseases, Konya, Turkey. 143University Hospitals Leuven, Leuven, Belgium. 144Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France. 145Hôpital Erasme, Brussels, Belgium. 146CH Gonesse, Gonesse, France. 147Vascular Medicine, Georges Pompidou Hospital, APHP, Paris, France. 148Division of Pulmonary and Critical Care, University of Miami, Miami, USA. 149Guanarteme Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 150Regional University Hospital of Malaga, Malaga, Spain. 151Aix-Marseille Université, Marseille, France. 152Department of General Paediatrics, Hôpital Bicêtre, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France. 153CHU de La Timone, Marseille, France. 154Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. 155Infectious Diseases Horizontal Technlogy Centre, A*STAR; Singapore Immunology Network, A*STAR, Singapore. 156Department of Pediatrics, Complejo Hospitalario Universitario Insular-Materno Infantil, Canarian Health System, Las Palmas de Gran Canaria, Spain. 157Regional Universitary Hospital of Malaga, Málaga, Spain. 158Hospital Universitario Marqués de Valdecilla, Santander, Spain. 159Ataturk University Medical Faculty, Erzurum, Turkey. 160Bilkent University, Department of Molecular Biology and Genetics, Ankara, Turkey. 161Department of Laboratory Medicine, Karolinska Institutet, SE14186, Stockholm, Sweden. 162L'Hôpital Foch, Suresnes, France. 163Department of Immunology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. 164APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 165Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona; CIBERER U759, ISCiii Madrid, Spain. 166Hospices Civils de Lyon, Lyon, France. 167Université de Lille, Inserm U1285, CHU Lille, Paris, France. 168Departement of General Pediatrics, University Hospital Robert Debré, APHP, Paris, France. 169Necmettin Erbakan University, Konya, Turkey. 170Germans Trias i Pujol Hospital, Badalona, Spain. 171Medical intensive care unit. Hopital de la Croix-Rousse. Hospices Civils de Lyon, Lyon, France. 172Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus., Barcelona, Spain. 173Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain, EU. University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. 174Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona, Spain. 175Consorcio Hospital General Universitario, Valencia, Spain. 176APHP Hôpitaux Universitaires Paris-Sud, Paris, France. 177Virology unit, Université de Paris, Cohin Hospital, APHP, Paris, France. 178Hospital San Pedro, Logroño, Spain. 179Respiratory medicine, Georges Pompidou Hospital, APHP, Paris, France. 180Dept. Immunology, Hospital Clínico San Carlos, Madrid, Spain. 181Service de Médecine Intensive Réanimation, Institut de Cardiologie, Hopital Pitié-Salpêtrière, Paris, France. 182CHRU de Nancy, Hôpital d'Enfants, Vandoeuvre, France. 183Chair of Nephrology, University of Brescia, Brescia, Italy. 184Department of Immunology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. 185Clínica Universidad de Navarra, Madrid, Spain. 186HUS Helsinki University Hospital, Children and Adolescents, Rare Disease Center, and Inflammation Center, Adult Immunodeficiency Unit, Majakka, Helsinki, Finland. 187Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain. 188Hopital Européen Georges Pompidou, Paris, France. 189Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 190Critical Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 191CHU de Saint Etienne, Saint-Priest-en-Jarez, France. 192Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 193Gustave Roussy Cancer Campus, Villejuif, France. 194Intensive Care Unit, Avicenne Hospital, APHP, Bobigny, France. 195Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, Paris University, Paris, France. 196Department of Internal Diseases and Pediatrics, Primary Immune Deficiency Research Lab, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium. 197Department of Internal Medicine, Université de Paris, INSERM, U970, PARCC, F-75015, Paris, France. 198First Division of Anesthesiology and Critical Care Medicine, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 199Intensive Care Department, Hospital Universitari MutuaTerrassa, Universitat Barcelona, Terrassa, Spain. 200Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 201Infanta Leonor University Hospital, Madrid, Spain. 202Hematology Department, ASST Spedali Civili di Brescia, Brescia, Italy. 203Pneumologie, Hôpital Avicenne, APHP, INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France. 204Dermatology unit, Laboratoire GAD, INSERM UMR1231 LNC, université de Bourgogne, Dijon, France. 205University Hospital of Burgos, Burgos, Spain. 206Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 207Department of Chest Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 208CHU de Caen, Caen, France. 209Sorbonne Université, Service de Médecine Intensive Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. 210General Intensive Care Unit, Konya Training and Research Hospital, Konya, Turkey. 211CHU de Nancy, Nancy, France. 212University of Lyon, CIRI, INSERM U1111, National referee centre RAISE, Pediatric Rheumatology, HFME, Hospices Civils de Lyon, Lyon, France. *Leader of the COVID-clinicians group., COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT., Imagine COVID Group Christine Bole-Feysot1, Stanislas Lyonnet1*, Cécile Masson1, Patrick Nitschke1, Aurore Pouliet1, Yoann Schmitt1, Frederic Tores1, Mohammed Zarhrate1 1Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cardiergues14, Eric D’ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent V. E. Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Treoux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22Rouen - SMIT, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d'Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28Bordeaux - SMIT, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Colombes - Louis Mourier - Gynécologie, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT; (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35hôpital la timone, Marseille, France. 36Paris - Bichat - SMIT, France., The Milieu Intérieur Consortium Laurent Abel1, Andres Alcover2, Hugues Aschard2, Kalla Astrom3, Philippe Bousso2, Pierre Bruhns2, Ana Cumano2, Caroline Demangel2, Ludovic Deriano2, James Di Santo2, Françoise Dromer2, Gérard Eberl2, Jost Enninga2, Jacques Fellay4, Ivo Gomperts-Boneca2, Milena Hasan2, Serge Hercberg5, Olivier Lantz6, Hugo Mouquet2, Etienne Patin2, Sandra Pellegrini2, Stanislas Pol7, Antonio Rausell8, Lars Rogge2, Anavaj Sakuntabhai2, Olivier Schwartz2, Benno Schwikowski2, Spencer Shorte2, Frédéric Tangy2, Antoine Toubert9, Mathilde Touvier10, Marie-Noëlle Ungeheuer2, Matthew L. Albert11*, Darragh Duffy2*, Lluis Quintana-Murci2* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine. 9Hôpital Saint-Louis, Paris, France. 10Université Paris 13, Paris, France. 11In Sitro. *Co-coordinators of the Milieu Intérieur Consortium. Additional information can be found at: https://www.pasteur.fr/labex/milieu-interieur., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cardièrgues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d'Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M'Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France . 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, BORDEAUX. 16Hôpital Hotel Dieu, APHP, Paris, France. 17ervice des explorations fonctionnelles, Hôpital Bichat- Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anne Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, O. Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno de Jong12, Rutger Koning4, Mourik van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Bennedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Netherlands. 3Experimental Immunology, Amsterdam UMC, Netherlands. 4Department of Neurology, Amsterdam UMC, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Netherlands. 7Department of Pathology, Amsterdam UMC, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Netherlands. 10Amsterdam UMC, THE NETHERLANDS Biobank Core Facility, Amsterdam UMC, Netherlands. 11Department of Radiology, Amsterdam UMC, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Netherlands. 18Department of Neurology, Amsterdam UMC, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University., Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco; Chan Zuckerberg Biohub, San Francisco, CA, United States. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID research lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Bambino Gesù Children's Hospital, Rome, Italy; Dept. Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy, Rome, Italy, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid 28046, Spain, EU, Madrid, Spain, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL- Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63University of Siena, Siena, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Lab, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children's Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, Dhaka, Bangladesh. 75Amsterdam UMC, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, United States. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62- IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit; funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The “Milieu Intérieur” cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence “Milieu Intérieur” Grant (ANR-10-LABX-69-01) (PI: L QuintanaMurci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant “DIGITAL COVID” (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health “Programme Hospitalier de Recherche Clinique Inter regional 2013”, by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d’Excellence”, reference ANR15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw; NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e comorbidita”). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program (“poste d’accueil Inserm”). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association “Turner et vous” for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support.
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- 2020
17. Determinants of the use of nonpharmacological analgesia for labor pain management: a national population-based study
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Babak Khoshnood, Béatrice Blondel, A A Chantry, Marie-Pierre Bonnet, Camille Le Ray, Jade Merrer, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Cité - École de sages-femmes Baudelocque (UPCité ESF Baudelocque), Université Paris Cité (UPCité), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), French Ministry of Health (Direction de la Recherche, des Etudes, de l'Evaluation et des Statistiques [DREES])French Ministry of Health (Direction Generale de la Sante [DGS])French Ministry of Health (Direction Generale de l'Organisation des Soins [DGOS])Sante publique FranceUniversite de Paris-Paris Descartes UniversityMustela FoundationFondation de Francegeneral directorate of health (DGS)national health insurance fund for employees (CNAM-TS)Institut National de la Sante et de la Recherche Medicale (Inserm)Appeared in source as:French national institute of health and medical research (Inserm)Inserm Cancer Plan, Lallemant, Christopher, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Paris - École de sages-femmes Baudelocque (UP ESF Baudelocque), Université de Paris (UP), Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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medicine.medical_specialty ,Cross-sectional study ,Population ,Neuraxial analgesia ,Nonpharmacological analgesia ,Prenatal care ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,030202 anesthesiology ,medicine ,Humans ,Pain Management ,education ,Obstetric analgesia ,Labor Pain ,education.field_of_study ,Vaginal delivery ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,Labor pain ,Odds ratio ,medicine.disease ,Confidence interval ,3. Good health ,Analgesia, Epidural ,Cross-Sectional Studies ,Anesthesiology and Pain Medicine ,Neurology ,Physical therapy ,Labor pain management ,Analgesia, Obstetrical ,Female ,Perinatalepidemiology ,France ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
International audience; Besides neuraxial analgesia, nonpharmacological methods are also proposed to help women coping with pain during labor. We aimed to identify the individual and organizational factors associated with the use of nonpharmacological analgesia for labor pain management. Women who attempted vaginal delivery with labor analgesia were selected among participants included in the 2016 National Perinatal Survey, a population-based cross-sectional study. Labor analgesia was studied as neuraxial analgesia alone, nonpharmacological analgesia alone, and neuraxial and nonpharmacological analgesia combined. The associations were studied using multilevel multinomial logistic regression. Among the 9231 women included, 62.4% had neuraxial analgesia alone, 6.4% had nonpharmacological analgesia alone, and 31.2% had both. Nonpharmacological analgesia alone or combined with neuraxial analgesia were both associated with high educational level (adjusted odds ratio 1.55; 95% confidence interval [CI], 1.08-2.23 and 1.39; 95% CI, 1.18-1.63), antenatal preference to deliver without neuraxial analgesia, and public maternity unit status. Nonpharmacological analgesia alone was more frequent among multiparous women, and in maternity units with an anesthesiologist not dedicated to delivery unit (1.57; 95% CI, 1.16-2.12) and with the lowest midwife workload (2.15; 95% CI, 1.43-3.22). Neuraxial and nonpharmacological analgesia combined was negatively associated with inadequate prenatal care (0.70; 95% CI, 0.53-0.94). In France, most women who had nonpharmacological analgesia during labor used it as a complementary method to neuraxial analgesia. The use of nonpharmacological analgesia combined with neuraxial analgesia mainly depends on the woman's preference, but also on socioeconomic factors, quality of prenatal care, and care organization.
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- 2020
18. Antenatal HIV screening: results from the National Perinatal Survey, France, 2016
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Cécile Sommen, Thi-Chiên Tran, Florence Lot, Françoise Cazein, Josiane Pillonel, Béatrice Blondel, Camille Bonnet, French National Public Health Agency, Centre de Recherche en Epidémiologie et StatistiqueS, Partenaires INRAE, French Ministry of Health (Direction de la Recherche, des Etudes, de l'Evaluation et des Statistiques (DREES)), French Ministry of Health (Direction Générale de la Santé (DGS)), French Ministry of Health (Direction Générale de l'Organisation des Soins (DGOS)), and Sante publique France
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Epidemiology ,[SDV]Life Sciences [q-bio] ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,0302 clinical medicine ,Hiv test ,Prenatal Diagnosis ,Surveys and Questionnaires ,Mass Screening ,030212 general & internal medicine ,Pregnancy Complications, Infectious ,pregnancy ,determinants ,trends ,health ,women ,030219 obstetrics & reproductive medicine ,Transmission (medicine) ,Obstetrics ,Health Policy ,Medical record ,Prenatal Care ,maternal characteristics ,Female ,France ,antenatal HIV screening ,national perinatal survey ,Adult ,medicine.medical_specialty ,Newly diagnosed ,03 medical and health sciences ,antenatal care ,Virology ,medicine ,Humans ,Quality Indicators, Health Care ,Antenatal HIV screening ,business.industry ,Research ,Public Health, Environmental and Occupational Health ,Odds ratio ,Infectious Disease Transmission, Vertical ,Cross-Sectional Studies ,Socioeconomic Factors ,Health Care Surveys ,Pregnant Women ,business ,Program Evaluation - Abstract
Background Universal antenatal HIV screening programmes are an effective method of preventing mother-to-child transmission. Aims To assess the coverage and yield of the French programme on a nationally representative sample of pregnant women, and predictive factors for being unscreened or missing information on the performance/ result of a HIV test. Methods Data came from the medical records of women included in the cross-sectional 2016 French National Perinatal Survey. We calculated odds ratios (OR) to identify factors for being unscreened for HIV and for missing information by multivariable analyses. Results Of 13,210 women, 12,782 (96.8%) were screened for HIV and 134 (1.0%) were not; information was missing for 294 (2.2%). HIV infection was newly diagnosed in 19/12,769 (0.15%) women screened. The OR for being unscreened was significantly higher in women in legally registered partnerships (OR: 1.3; 95% CI: 1.1–1.6), with 1–2 years of post-secondary schooling (OR: 1.6; 95% CI: 1.2–2.1), part-time employment (OR: 1.4; 95% CI: 1.1–1.8), inadequate antenatal care (OR: 1.9; 95% CI: 1.5–2.4) and receiving care from > 1 provider (OR: 1.8; 95% CI: 1.1–2.8). The OR of missing information was higher in multiparous women (OR: 1.4; 95% CI: 1.2–1.5) and women cared for by general practitioners (OR: 1.4; 95% CI: 1.1–1.9). Conclusions The French antenatal HIV screening programme is effective in detecting HIV among pregnant women. However, a few women are still not screened and awareness of the factors that predict this could contribute to improved screening levels.
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- 2019
19. Iron‐fortified formula use in young children and association with socioeconomic factors in the French nationwide ELFE cohort
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Sacri, Anne-Sylvia, de Lauzon-Guillain, Blandine, Dufourg, Marie-Noëlle, Bois, Corinne, Charles, Marie Aline, Chalumeau, Martin, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service départemental de PMI [Nanterre], Conseil départemental des Hauts-de-Seine, Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Paris Diderot Université Sorbonne Paris Cité - Secteur Français des Aliments de l'Enfance, French Ministry of Health 'DGOS PHRC régional 2014' AOR14053- Ministry of Higher Education & Scientific Research (MHESR)- Institut national de la jeunesse et de l'éducation populaire (INJEP) - French National Research Agency (ANR), ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Funding was received from Paris Diderot University - Sorbonne Paris Cité for a doctoral grant for Dr Sacri. Funding was received from institutions for another research project: Secteur Français des Aliments de l’Enfance (Dr Sacri and Pr Chalumeau), French Ministry of Health 'DGOS PHRC régional 2014 n° AOR14053' (Dr Sacri and Pr Chalumeau).
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Population-based cohort study ,Primary prevention ,Iron deficiency ,Infant formula ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Socioeconomic factors - Abstract
Marie Aline Charles, PhD and Martin Chalumeau, MD, PhD : are equally contribution.; International audience; AIM:To study the rate of iron-fortified infant formula (IFF) use in young children in France and its association with socioeconomic factors.METHODS:The ELFE national birth cohort included, in 2011, 18 329 living births in 349 hospitals randomly selected. The present analyses were restricted to children with follow-up at age two years. Milk consumption was evaluated by parental telephone interview, and its association with socioeconomic factors was studied.RESULTS:The 12 341 analysed children had a mean age of 26 months; 50% were girls. Rate of IFF use before two years old and at two years old was 65% and 43%, respectively. At age two years, use of IFF was lower with young age of the mother (adjusted OR [aOR] = 0.4, 95% CI: 0.3-0.5), low educational level (aOR = 0.7, 95% CI: 0.6-0.9), high parity (aOR = 0.3, 95% CI 0.2-0.4), and mother smoking (aOR = 0.8, 95% CI: 0.7-0.9) as well as low household income (aOR = 0.5, 95% CI: 0.4-0.7), and parents' unemployment (aOR = 0.7, 95% CI: 0.5-0.9).CONCLUSION:In this national population-based study, the rate of implementation of the ID prevention strategy was much lower at two years old than before two years old, and significantly lower in disadvantaged populations.
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- 2019
20. Implementation of Control Strategies for Sterile Insect Techniques
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Pierre-Alexandre Bliman, Yves Dumont, Olga Vasilieva, Daiver Cardona-Salgado, Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidad Autónoma de Occidente (UAO), Botanique et Modélisation de l'Architecture des Plantes et des Végétations (UMR AMAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), University of Pretoria [South Africa], Universidad del Valle [Cali] (Univalle), Support from the Colciencias – ECOS-Nord Program (Colombia: Project CI-71089, France: Project C17M01) is kindly acknowledged. DC and OV were supported by the inter-institutional cooperation program MathAmsud (18-MATH-05). This study was part of the Phase 2A ‘SIT feasibility project against Aedes albopictus in Reunion Island’, jointly funded by the French Ministry of Health (Convention 3800/TIS) and the European Regional Development Fund (ERDF) (Convention No. 2012-32122 and Convention No. GURDTI 2017-0583-0001899). YD was (partially) supported by the DST/NRF SARChI Chair in Mathematical Models and Methods in Biosciences and Bioengineering at the University of Pretoria (grant 82770). YD also acknowledges the support of the Visiting Professor Granting Scheme from the Office of the Deputy Vice Chancellor for Research Office of the University of Pretoria., Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), France: Project C17M01) is kindly acknowledged. Daiver Cardona-Salgado and Olga Vasilieva were supported by the inter-institutional cooperation program Math-Amsud (18-MATH-05). This study was part of the Phase 2A ‘SIT feasibility project against Aedes albopictus in Reunion Island’, jointly funded by the French Ministry of Health (Convention 3800/TIS) and the European Regional Development Fund (ERDF) (Convention No. 2012-32122 and Convention No. GURDTI 2017-0583-0001899). Yves Dumon was (partially) supported by the DST/NRF SARChI Chair in Mathematical Models and Methods in Biosciences and Bioengineering at the University of Pretoria (grant 82770), Universidad Autonoma de Occidente (UAO), and Université de Pretoria
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Male ,Mosquito Control ,Computer science ,L73 - Maladies des animaux ,01 natural sciences ,010305 fluids & plasmas ,Disease Outbreaks ,Sterile insect technique ,Aedes ,Convergence (routing) ,Control (linguistics) ,Mathematics - Optimization and Control ,0303 health sciences ,education.field_of_study ,Applied Mathematics ,Population size ,Open-loop controller ,General Medicine ,Modeling and Simulation ,[MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC] ,Control biológico de plagas ,General Agricultural and Biological Sciences ,Modèle mathématique ,Statistics and Probability ,Population ,Mosquito Vectors ,Global stability ,Pests - Biological control ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Exponential convergence ,Analyse quantitative ,Control theory ,0103 physical sciences ,FOS: Mathematics ,Animals ,education ,Pest Control, Biological ,Quantitative Biology - Populations and Evolution ,Infertility, Male ,030304 developmental biology ,Open-loop and closed-loop control ,Control mode ,General Immunology and Microbiology ,Saturated control ,Sterile Insect Technique ,Populations and Evolution (q-bio.PE) ,Stérilisation ,Lutte biologique ,Optimization and Control (math.OC) ,Periodic impulsive control ,FOS: Biological sciences ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Constant (mathematics) - Abstract
In this paper, we propose a sex-structured entomological model that serves as a basis for design of control strategies relying on releases of sterile male mosquitoes (Aedes spp) and aiming at elimination of the wild vector population in some target locality. We consider different types of releases (constant and periodic impulsive), providing necessary conditions to reach elimination. However, the main part of the paper is focused on the study of the periodic impulsive control in different situations. When the size of wild mosquito population cannot be assessed in real time, we propose the so-called open-loop control strategy that relies on periodic impulsive releases of sterile males with constant release size. Under this control mode, global convergence towards the mosquito-free equilibrium is proved on the grounds of sufficient condition that relates the size and frequency of releases. If periodic assessments (either synchronized with releases or more sparse) of the wild population size are available in real time, we propose the so-called closed-loop control strategy, which is adjustable in accordance with reliable estimations of the wild population sizes. Under this control mode, global convergence to the mosquito-free equilibrium is proved on the grounds of another sufficient condition that relates not only the size and frequency of periodic releases but also the frequency of sparse measurements taken on wild populations. Finally, we propose a mixed control strategy that combines open-loop and closed-loop strategies. This control mode renders the best result, in terms of overall time needed to reach elimination and the number of releases to be effectively carried out during the whole release campaign, while requiring for a reasonable amount of released sterile insects., 30 pages, 9 figures
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- 2018
21. Development and Validation of the QUALI-PALLI-FAM Questionnaire for Assessing Relatives' Perception of Quality of Inpatient Palliative Care: A Prospective Cross-Sectional Survey
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Frédéric Guirimand, Carole Bouleuc, Isabelle Vedel, Laure Copel, Louise Geoffroy, Philippe Aegerter, Marine Sahut d’Izarn, Patricia Martel-Samb, Xavier Grenet, Karima Nfissi, Anne Abel, Laurence Gineston, Yael Tibi-Lévy, Sylvie Rostaing, Jean-François Richard, Bernard Devalois, Kate Vincent, Hélène Godard, Stéphane Picard, Christian Guy-Coichard, Véronique Ghadi, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Curie [Paris], Hôpital Ambroise Paré [AP-HP], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe Hospitalier Diaconesses Croix Saint-Simon, CY Cergy Paris Université (CY), Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Ministère des Affaires Sociales et de la Santé: 2009-04 Assistance publique-Hôpitaux de Paris: NI10052 12059, NCT02814682, Funding: This study was supported by a grant from the French Ministry of Health ( PreQHos 2009-04 ) and sponsored by the Assistance Publique-Hôpitaux de Paris ( NI10052 )., The investigators thank the members of the QUALI-PALLI Group: Anne Abel, Laure Copel, Louise Geoffroy, Laurence Gineston, H?l?ne Godard, Xavier Grenet, Karima Nfissi, Jean-Fran?ois Richard, Sylvie Rostaing, Yael Tibi-L?vy, Isabelle Vedel, Kate Vincent, and the Clinical Research Unit team that worked on QUALI-PALLI (Layde Meaude, Sylvie Laot-Cabon, Sarah Gaston-Dreyfus, Audrey Angelard, Yasmine Saidji, Karima Mesbahi, and Wen Teng). Funding: This study was supported by a grant from the French Ministry of Health (PreQHos 2009-04) and sponsored by the Assistance Publique-H?pitaux de Paris (NI10052). Ethical approval: This study was approved by a regional ethics committee (#12059, Comit? de Protection des Personnes CPP ?le de France XI, Saint Germain-en-Laye, France) and was registered on clinicaltrials.gov (NCT02814682). All participants were duly informed, and oral consent was obtained before the research. According to French health regulations, no written informed consent was required, as this was an observational study using registered data. Data sharing: The data sets generated and/or analyzed during the present study are not publicly available to protect confidentiality, but aggregated data are available from the corresponding author on reasonable request. The authors declare no conflicts of interest., and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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medicine.medical_specialty ,family ,Palliative care ,Psychometrics ,Cross-sectional study ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Context (language use) ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,quality of health care ,Cronbach's alpha ,Surveys and Questionnaires ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,General Nursing ,Inpatients ,outcome measure ,business.industry ,questionnaire ,Palliative Care ,Reproducibility of Results ,Exploratory factor analysis ,3. Good health ,Distress ,Cross-Sectional Studies ,Anesthesiology and Pain Medicine ,validation study ,030220 oncology & carcinogenesis ,Scale (social sciences) ,Family medicine ,Quality of Life ,Perception ,Neurology (clinical) ,business - Abstract
International audience; Context: Relatives of patients receiving palliative care are at risk for psychological and physical distress, and their perception of quality of care can influence patients' quality of life. Objectives: The purpose of this study was to develop and validate the QUALI-PALLI-FAM questionnaire (QUAlity of PALLIative car from FAMilies' perspective) to measure families' perception of and satisfaction with palliative care. Methods: An exploratory factor analysis was conducted, and we evaluated the questionnaire's internal consistency using Cronbach's alpha, its stability across various strata, and the correlation between the QUALI-PALLI-FAM (factors, total score, and global satisfaction) and the total score of the FAMCARE (FAMily satisfaction with CARE) questionnaire. Results: This multicentric prospective cross-sectional survey was conducted in seven French hospitals, namely, three palliative care units and four standard medical units with a mobile palliative care team. The questionnaire was completed by 170 relatives of patients (more than 90% of patients had advanced cancer). The final questionnaire included 14 items across three domains: organization of care and availability of caregivers, medical information provision, and confidence and involvement of relatives. Internal consistency was good for all subscales (Cronbach's α = 0.74–0.86). Our questionnaire was stable across various strata: age and gender (patients and relatives), Palliative Performance Scale scores, and care settings. The QUALI-PALLI-FAM total score was correlated with the total FAMCARE score. Conclusion: The QUALI-PALLI-FAM appears to be a valid, reliable, and well-accepted tool to explore relatives' perception of quality of inpatient palliative care and complements the QUALI-PALLI-PAT questionnaire. Further testing is required in various settings and countries.
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- 2021
22. Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting
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Soilly, Al, Robert-Viard, C, Besse, C, Bruel, Al, Gerard, B, Boland, A, Piton, A, Duffourd, Y, Muller, J, Poë, C, Jouan, T, El Doueiri, S, Faivre, L, Bacq-Daian, D, Isidor, B, Genevieve, D, Odent, S, Philip, N, Doco-Fenzy, M, Lacombe, D, Asensio, Ml, Deleuze, Jf, Binquet, C, Thauvin-Robinet, C, Lejeune, C, Arpin, S, Blanchet, P, Blesson, S, Boute-Benejean, O, Busa, T, Colin, E, Coubes, C, Devillard, F, Edery, P, El Chehadeh, S, Fradin, M, Goldenberg, A, Guerrot, A-M, Herenger, Y, Houcinat, N, Jean-Marcais, N, Jouk, P., Lambert, L, Lavillaureix, A, Legendre, M, Leheup, B, Manouvrier, S, Mercier, S, Moutton, S, Nizon, M, Pasquier, L, Petit, F, Pinson, L, Poirsier, C, Pons, L, Putoux, A, Quelin, C, Renaud, M, Rossi, M, Sorlin, A, Spodenkiewicz, M, Thevenon, J, Toutain, A, Van-Gils, J, Vanlerberghe, C, Verloes, A, Vincent, M, Vincent-Delorme, C, Willems, M, Ziegler, A, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de Recherche en Génomique Humaine (CNRGH), Laboratoire de Diagnostic Génétique [CHU Strasbourg], Université de Strasbourg (UNISTRA)-CHU Strasbourg, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), FHU TRANSLAD (CHU de Dijon), and This study was funded by the French Ministry of Health as part of the 2015 Medico-Economic Research Program.
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Exome sequencing ,MESH: France ,MESH: Exome ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,Cost analysis ,Intellectual disability ,Micro-costing ,MESH: Intellectual Disability - Abstract
Background: With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers.Methods: A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH). The analysis was conducted from the point of view of these two ES stakeholders. All of the resources (labor, equipment, disposables and reagents, reusable material) required to analyze blood samples were identified, collected and valued. Several sensitivity analyses were performed.Results: The unit nominal cost per ES diagnostic test for ID was estimated to be €2,019.39. Labor represented 50.7% of the total cost. The analytical step (from the preparation of libraries to the analysis of sequences) represented 88% of the total cost. Sensitivity analyses suggested that a simultaneous price decrease of 20% for the capture kit and 50% for the sequencing support kit led to an estimation of €1,769 per ES diagnostic test for ID.Conclusion: This is the first estimation of ES cost to be done in the French setting of ID diagnosis. The estimation is especially influenced by the price of equipment kits, but more generally by the organization of the centers involved in the different steps of the analysis and the time period in which the study was conducted. This information can now be used to define an adequate tariff and assess the efficiency of ES.Trial registration: ClinicalTrials.gov identifier NCT03287206 on September 19, 2017.
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- 2023
23. Multivariate classification of Brugada syndrome patients based on autonomic response to exercise testing
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Philippe Mabo, Pedro Gomis, Daniel Romero, Alfredo Hernandez, Mireia Calvo, Nathalie Behar, Virginie Le Rolle, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recerca en Enginyeria Biomèdica [Catalunya] (CREB), Universitat Politècnica de Catalunya [Barcelona] (UPC), Enginyeria de Sistemes, Automàtica i Inf.Ind. (ESAII), CIBER de Enfermedades Raras (CIBERER), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], French Ministry of Health (Programme Hospitalier de Recherche Clinique - PHRC Regional) [ID RCB 2007-A00887-46, 07/28-645], la Caixa Foundation, Lefoulon-Delalande Foundation, la Caixa Foundation (Spain), Lefoulon-Delalande Foundation (France), French Ministry of Health (Programme Hospitalier de Recherche Clinique - PHRC Regional), Universitat Politècnica de Catalunya. Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, Universitat Politècnica de Catalunya. B2SLab - Bioinformatics and Biomedical Signals Laboratory, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recerca en Enginyeria Biomèdica [Catalunya] ( CREB ), Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Enginyeria de Sistemes, Automàtica i Inf.Ind. ( ESAII ), Service de cardiologie et maladies vasculaires, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Jonchère, Laurent
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Male ,Multivariate analysis ,HRV ,lcsh:Medicine ,[ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing ,030204 cardiovascular system & hematology ,Heart--Diseases--Case studies ,Linear Discriminant Analysis ,Incremental exercise ,Machine Learning ,Electrocardiography ,Mathematical and Statistical Techniques ,0302 clinical medicine ,Heart Rate ,Medicine and Health Sciences ,Medicine ,Heart rate variability ,Public and Occupational Health ,[ SDV.IB ] Life Sciences [q-bio]/Bioengineering ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS ,Brugada Syndrome ,Brugada syndrome ,Multidisciplinary ,medicine.diagnostic_test ,Applied Mathematics ,Simulation and Modeling ,Discriminant Analysis ,Middle Aged ,Sports Science ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Bioassays and Physiological Analysis ,multivariate analysis ,Physical Sciences ,Cardiology ,Female ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,medicine.symptom ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,Algorithms ,Statistics (Mathematics) ,Arrhythmia ,Research Article ,Adult ,Computer and Information Sciences ,medicine.medical_specialty ,Ciències de la salut::Medicina [Àrees temàtiques de la UPC] ,Autonomic Nervous System ,Research and Analysis Methods ,Asymptomatic ,Young Adult ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Artificial Intelligence ,Cor -- Malalties ,Internal medicine ,Heart rate ,Anàlisi multivariable ,Humans ,Sports and Exercise Medicine ,Statistical Methods ,Exercise ,Aged ,[SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing ,[SDV.IB] Life Sciences [q-bio]/Bioengineering ,business.industry ,Electrophysiological Techniques ,lcsh:R ,Biology and Life Sciences ,Physical Activity ,autonomic response ,Linear discriminant analysis ,medicine.disease ,Physical Fitness ,Exercise Test ,lcsh:Q ,Cardiac Electrophysiology ,business ,Mathematics ,030217 neurology & neurosurgery ,Forecasting - Abstract
International audience; Ventricular arrhythmias in Brugada syndrome (BS) typically occur at rest and especially during sleep, suggesting that changes in the autonomic modulation may play an important role in arrhythmogenesis. The autonomic response to exercise and subsequent recovery was evaluated on 105 patients diagnosed with BS (twenty-four were symptomatic), by means of a time-frequency heart rate variability (HRV) analysis, so as to propose a novel predictive model capable of distinguishing symptomatic and asymptomatic BS populations. During incremental exercise, symptomatic patients showed higher HFnu values, probably related to an increased parasympathetic modulation, with respect to asymptomatic subjects. In addition, those extracted HRV features best distinguishing between populations were selected using a two-step feature selection approach, so as to build a linear discriminant analysis (LDA) classifier. The final features subset included one third of the total amount of extracted autonomic markers, mostly acquired during incremental exercise and active recovery, thus evidencing the relevance of these test segments in BS patients classification. The derived predictive model showed an improved performance with respect to previous works in the field (AUC= 0.92 +/- 0.01; Se= 0.91 +/- 0.06; Sp= 0.90 +/- 0.05). Therefore, based on these findings, some of the analyzed HRV markers and the proposed model could be useful for risk stratification in Brugada syndrome.
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- 2018
24. Management of epistaxis associated with oral antithrombotic drugs in emergency department and impact on prescription thereafter
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Jacques Bouget, Frédéric Balusson, Pierre‐Marie Roy, Damien Viglino, Laure Pavageau, Karine Lacut, Emmanuel Oger, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Grenoble, Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), DGOS/French Ministry of Health, Grant/Award Number: PHRC-12-009-0243, and National Clinical Research Hospital Program (PHRC)
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medication decision ,Otorhinolaryngology ,emergency ,epistaxis ,[SDV]Life Sciences [q-bio] ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,antithrombotic drugs ,management - Abstract
International audience; OBJECTIVES: To describe management, and to assess factors associated with antithrombotic prescription thereafter in patients who had epistaxis referred to emergency department (ED). DESIGN: Prospective cohort study. From EDs, clinical, biological and hospital data were collected. The clinical database was linked to the French Health Insurance Database where we retrieved antithrombotic drug deliveries in a 3-month period before and after referral. SETTING: Multicentric population-based cohort study within five well-defined areas. PARTICIPANTS: We considered 306 patients referred for epistaxis with a stable oral antithrombotic regimen before referral. MAIN OUTCOME MEASURES: We considered management, hospital outcome and case fatality. Antithrombotic prescription in a 3-month follow-up period was categorised into three classes: no change, class change, or discontinuation. During follow-up, hospitalisation for epistaxis or ischaemic events was searched. RESULTS: Among 306 adult individuals (mean age: 76 years), 166 took oral anticoagulant and 140 an antiplatelet drug. Blood transfusion was needed in 13.7% of patients and anterior packing alone in 61%. Half of the patients were hospitalised; 301 were discharged alive. Considering antithrombotic prescription thereafter we observed no change in 219 patients (72.8%), class changes in 47 patients (15.6%) and discontinuation in 35 patients (11.6%). We identified four independent predictors for antithrombotic prescription: hospitalisation (vs. returning home, p = .05), age (p = .03), haemoglobin level (p = .03) and oral anticoagulant (vs. antiplatelet agent, p
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- 2023
25. Infant neurodevelopment and behavior in Guadeloupe after lead exposure and Zika maternal infection during pregnancy
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Kadawathagedara, M, Muckle, G, Quenel, P, Michineau, L, Le Bot, B, Hoen, B., Tressieres, B, Multigner, L, Chevrier, C, Cordier, S, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Département des sciences en santé environnementale (DEESSE), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU Pointe-à-Pitre/Abymes [Guadeloupe], This research was funded by: the Agence Française pour la Biodiversité (AFB/2018/172) as part of the national ECOPHYTO PLAN II, within the framework of the French National Research Programme for Environmental and Occupational Health (PNR-EST), coordinated by ANSES, the Regional Health Agency of Guadeloupe (ARS/VSS/2018), and the European Union’s Horizon 2020 Research and Innovation Programme through the ZIKAlliance project (under Grant Agreement No. 734548). The ZIKA_DFA_FE/BB studies were supported by the French Ministry of Health (Soutien Exceptionnel à la Recherche et à l′Innovation)., Internationale, European Project: 734548,ZIKAlliance(2016), Chard-Hutchinson, Xavier, and A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID
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Behavior ,Infancy ,[SDV]Life Sciences [q-bio] ,General Neuroscience ,Development ,Toxicology ,[SDV] Life Sciences [q-bio] ,[SDV.TOX] Life Sciences [q-bio]/Toxicology ,Zika ,Lead ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Prenatal exposure ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Biomarkers - Abstract
International audience; BACKGROUND: Prenatal lead exposure is known to have neurotoxic effects on the developing fetus, while some viral infections may have a tropism for the central nervous system. Our objective was to study whether the effects of prenatal lead exposure on infant development and behaviors at 18 months of age are modified by the occurrence of a maternal infection to Zika virus (ZIKV) during pregnancy. METHODS: During the ZIKV epidemic in Guadeloupe in 2016 a cohort of pregnant women was set up. Blood samples (pregnancy, childbirth and cord) (n = 297) enabled us to measure blood lead levels aimed to determine prenatal lead exposure and the likelihood of maternal infection during pregnancy (ZIKV status + vs -). The 18 months "Ages and Stages Questionnaire" (ASQ) was used to generate scores for global development, fine and gross motor skills, communication, problem solving, and personal-social skills. The questions from a longitudinal cohort study conducted in Canada (Québec) were used to generate hyperactivity, opposition, inattention and physical aggression scores. Associations were tested by multivariate linear regressions. RESULTS: Prenatal lead exposure was associated with delays in neurodevelopment at 18 months, reflected by lower scores in ASQ totals, and in the fine motor and problem-solving domains. Some of these associations appeared to be sex-specific, observed almost exclusively in boys (ASQ total, fine motor and personal-social scores). Prenatal lead exposure was not associated with behavioral scores. ZIKV infection during pregnancy was associated with a lower fine motor ASQ score, and higher scores for hyperactivity, opposition and physical aggression. Significant interaction between prenatal lead exposure and ZIKV status was observed with a lower personal-social score in ZIKV (-) only, and for hyperactivity and inattention scores, though some of these interactions (ASQ personal-social score, inattention score) were no longer significant when children with microcephaly were excluded from the analyses. DISCUSSION/CONCLUSION: Our study confirms previous findings of associations between prenatal exposure to lead at low levels and adverse neurodevelopmental outcomes during infancy and the particular vulnerability of boys. It suggests associations between ZIKV infection during pregnancy and adverse effects on a number of neurodevelopmental functions (fine motor function) and behaviors (opposition, hyperactivity), that need to be confirmed at later age. There is no strong evidence of interaction between ZIKV infection and lead exposure but both prenatal risk factors may affect fine motor function.
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- 2023
26. Rare pathogenic variants in WNK3 cause X-linked intellectual disability
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Sébastien Küry, Jinwei Zhang, Thomas Besnard, Alfonso Caro-Llopis, Xue Zeng, Stephanie M. Robert, Sunday S. Josiah, Emre Kiziltug, Anne-Sophie Denommé-Pichon, Benjamin Cogné, Adam J. Kundishora, Le T. Hao, Hong Li, Roger E. Stevenson, Raymond J. Louie, Wallid Deb, Erin Torti, Virginie Vignard, Kirsty McWalter, F. Lucy Raymond, Farrah Rajabi, Emmanuelle Ranza, Detelina Grozeva, Stephanie A. Coury, Xavier Blanc, Elise Brischoux-Boucher, Boris Keren, Katrin Õunap, Karit Reinson, Pilvi Ilves, Ingrid M. Wentzensen, Eileen E. Barr, Solveig Heide Guihard, Perrine Charles, Eleanor G. Seaby, Kristin G. Monaghan, Marlène Rio, Yolande van Bever, Marjon van Slegtenhorst, Wendy K. Chung, Ashley Wilson, Delphine Quinquis, Flora Bréhéret, Kyle Retterer, Pierre Lindenbaum, Emmanuel Scalais, Lindsay Rhodes, Katrien Stouffs, Elaine M. Pereira, Sara M. Berger, Sarah S. Milla, Ankita B. Jaykumar, Melanie H. Cobb, Shreyas Panchagnula, Phan Q. Duy, Marie Vincent, Sandra Mercier, Brigitte Gilbert-Dussardier, Xavier Le Guillou, Séverine Audebert-Bellanger, Sylvie Odent, Sébastien Schmitt, Pierre Boisseau, Dominique Bonneau, Annick Toutain, Estelle Colin, Laurent Pasquier, Richard Redon, Arjan Bouman, Jill. A. Rosenfeld, Michael J. Friez, Helena Pérez-Peña, Syed Raza Akhtar Rizvi, Shozeb Haider, Stylianos E. Antonarakis, Charles E. Schwartz, Francisco Martínez, Stéphane Bézieau, Kristopher T. Kahle, Bertrand Isidor, Clinical Genetics, Clinical sciences, Medical Genetics, Reproduction and Genetics, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), University of Exeter, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Greenwood Genetic Center, GeneDx [Gaithersburg, MD, USA], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Genève = University of Geneva (UNIGE), Yale School of Medicine [New Haven, Connecticut] (YSM), This work was granted by the French network of University Hospitals HUGO ('Hôpitaux Universitaires du Grand Ouest'), the French Ministry of Health, and and the Health Regional Agencies from Poitou-Charentes (represented by Frédérique Allaire), Bretagne, Pays de la Loire, and Centre-Val de Loire (HUGODIMS, 2013, RC14_0107). W.K.C. was supported by grants from Simons Foundation Autism Research Initiative, United
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MESH: Symporters ,Exome sequencing ,Male ,KCC2 ,Mutation, Missense ,MESH: Catalytic Domain ,Neurodevelopmental disease ,Protein Serine-Threonine Kinases ,X-linked intellectual disability ,MESH: Brain ,WNK3 ,SDG 3 - Good Health and Well-being ,Loss of Function Mutation ,Catalytic Domain ,MESH: Mental Retardation, X-Linked ,Humans ,Phosphorylation ,MESH: Hemizygote ,Genetics (clinical) ,Hemizygote ,MESH: Mutation, Missense ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,MESH: Phosphorylation ,Symporters ,Brain ,MESH: Loss of Function Mutation ,MESH: Protein Serine-Threonine Kinases ,MESH: Male ,Mental Retardation, X-Linked ,Maternal Inheritance ,MESH: Maternal Inheritance - Abstract
PURPOSE: WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown. METHOD: We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID). RESULTS: We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.Pro204Arg, p.Leu300Ser, p.Glu607Val) in WNK3 in 14 male individuals from 6 unrelated families. Affected individuals had identifier with variable presence of epilepsy and structural brain defects. WNK3 variants cosegregated with the disease in 3 different families with multiple affected individuals. This included 1 large family previously diagnosed with X-linked Prieto syndrome. WNK3 pathogenic missense variants localize to the catalytic domain and impede the inhibitory phosphorylation of the neuronal-specific chloride cotransporter KCC2 at threonine 1007, a site critically regulated during the development of synaptic inhibition. CONCLUSION: Pathogenic WNK3 variants cause a rare form of human X-linked identifier with variable epilepsy and structural brain abnormalities and implicate impaired phospho-regulation of KCC2 as a pathogenic mechanism.
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- 2022
27. Phospholipase A2 Receptor (PLA2R1) Sequence Variants in Idiopathic Membranous Nephropathy
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S. H. Powis, Robert Kleta, Marieke J H Coenen, Anne Boland-Augé, Peter W. Mathieson, Paul Brenchley, Hanna Debiec, Jack F.M. Wetzels, Johanne M. Groothuismink, Bénédicte Stengel, Horia Stanescu, Alan Medlar, Julia M. Hofstra, Pierre Ronco, Detlef Bockenhauer, Department of Human Genetics [Nijmegen], Radboud University Medical Center [Nijmegen], Department of Nephrology [Nijmegen, The Netherlands], Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre for Nephrology [London, UK], University College of London [London] (UCL), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Academic Renal Unit [Bristol, UK], University of Bristol [Bristol], School of Biomedicine [Manchester, UK], University of Manchester [Manchester], The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement 2012-305608 'European Consortium for High-Throughput Research in Rare Kidney Diseases' (EURenOmics)' (to P.W.M., P.E.B., R.K., J.F.M.W., P.R.), by the David and Elaine Potter Charitable Foundation (to S.H.P., R.K.), by the Dutch Kidney Foundation (J.M.H., grant KJPB11.021), and by the FrenchFoundation for Medical Research (H.D., P.R., grant 2012). The French Gn-Progress cohort was supported by grants from the French Ministry of Health (PHRC AOM 00022), the Ministry of Research (Decision d’aide 01P0513), and the Biomedicine Agency (AO Recherche et Greffes 2005)., Department of Human Genetics, Department of nephrology, Remodelage et Reparation du Tissu Renal, Centre for Nephrology, Equipe 10, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Academic Renal Unit, School of Biomedicine, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement 2012-305608 'European Consortium for High-Throughput Research in Rare Kidney Diseases' (EURenOmics)'(to P.W.M., P.E.B., R.K., J.F.M.W., P.R.), by the David and Elaine Potter Charitable Foundation (to S.H.P., R.K.), by the Dutch Kidney Foundation (J.M.H., grant KJPB11.021), and by the French Foundation for Medical Research (H.D., P.R., grant 2012). The French Gn-Progress cohort was supported by grants from the French Ministry of Health (PHRC AOM 00022), the Ministry of Research (Decision d'aide 01P0513), and the Biomedicine Agency (AO Recherche et Greffes 2005)., RONCO, Pierre, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Radboud University Medical Centre [Nijmegen, The Netherlands], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
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Male ,MESH: Sequence Analysis, DNA ,MESH: Glomerulonephritis, Membranous ,030232 urology & nephrology ,Glomerulonephritis, Membranous ,Exon ,0302 clinical medicine ,Coding region ,MESH: Genomic Structural Variation ,Renal disorder [IGMD 9] ,MESH: Aged ,Genetics ,Sanger sequencing ,0303 health sciences ,MESH: Middle Aged ,MESH: Polymorphism, Single Nucleotide ,MESH: Genetic Predisposition to Disease ,General Medicine ,Middle Aged ,3. Good health ,Nephrology ,symbols ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Female ,Adult ,dbSNP ,Sequence analysis ,Biology ,Polymorphism, Single Nucleotide ,Mental health [NCEBP 9] ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,03 medical and health sciences ,symbols.namesake ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,MESH: Receptors, Phospholipase A2 ,Humans ,Genetic Predisposition to Disease ,Allele ,1000 Genomes Project ,Genomic disorders and inherited multi-system disorders Molecular epidemiology [IGMD 3] ,Gene ,Aged ,030304 developmental biology ,MESH: Humans ,Receptors, Phospholipase A2 ,MESH: Adult ,Sequence Analysis, DNA ,Molecular biology ,MESH: Male ,Genomic Structural Variation ,MESH: Female - Abstract
International audience; The M-type receptor for phospholipase A2 (PLA2R1) is the major target antigen in idiopathic membranous nephropathy (iMN). Our recent genome-wide association study showed that genetic variants in an HLA-DQA1 and phospholipase A2 receptor (PLA2R1) allele associate most significantly with biopsy-proven iMN, suggesting that rare genetic variants within the coding region of the PLA2R1 gene may contribute to antibody formation. Here, we sequenced PLA2R1 in a cohort of 95 white patients with biopsy-proven iMN and assessed all 30 exons of PLA2R1, including canonical (GT-AG) splice sites, by Sanger sequencing. Sixty patients had anti-PLA2R1 in serum or detectable PLA2R1 antigen in kidney tissue. We identified 18 sequence variants, comprising 2 not previously described, 7 reported as rare variants (
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- 2013
28. Prenatal and childhood exposure to ambient air pollution and cognitive function in school-age children: Examining sensitive windows and sex-specific associations
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Guilbert, Ariane, Bernard, Jonathan Y., Peyre, Hugo, Costet, Nathalie, Hough, Ian, Seyve, Emie, Monfort, Christine, Philippat, Claire, Slama, Rémy, Kloog, Itai, Chevrier, Cécile, Heude, Barbara, Ramus, Franck, Lepeule, Johanna, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ben-Gurion University of the Negev (BGU), Institut des Géosciences de l’Environnement (IGE), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), This work as well as AG were funded by the Fondation de France (PAND-Alp grant 00089597).The EDEN cohort was supported by the Foundation for Medical Research, the National Agency for Research, the National Institute for Research in Public Health (IRESP: TGIR cohorte santé. 2008 program), the French Ministry of Health, the French Ministry of Research, the Inserm Bone and Joint Diseases National Research and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, the French National Institute for Population Health Surveillance, the French National Institute for Health Education, the European Union FP7 programs (FP7/2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects), the Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients), the French Agency for Environmental Health Safety, MutuelleGénérale de l’Education Nationale, the French National Agency for Food Security and the French-speaking Association for the Study of Diabetes and Metabolism.This study in the PELAGIE cohort was mainly supported by Inserm, the French National Research Agency (ANR-10-PRSP-0007) and the French Agency for Food, Environmental and Occupational Health and Safety (ANSES APR EST, 2009). The initial fundings of the PELAGIE cohort were Inserm, the French Ministries of Health, Labor, and Research, the French National Institute for Public Health Surveillance, the National Agency for Research, the French Agency for Environmental Health Safety (Afsset/ANSES), the European programs Hi-WATE and ENRIECO, and the Research Institute of Public Health.FR and HP received support under the program 'Investissements d’Avenir' launched by the French Government and implemented by ANR with the references ANR-17-EURE-0017 and ANR-10-IDEX-0001-02.The funders contributed to data collection but had no role in the design and conduct of the study, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The opinions, results, and conclusions herein are those of the authors and do not reflect the official policy or position of the funding sources., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-17-EURE-0017,FrontCog,Frontières en cognition(2017), and ANR-10-PRSP-0007,PEPSY(2010)
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DLNM ,PM ,IQ ,Pregnancy ,[SDV]Life Sciences [q-bio] ,Neurodevelopment ,NO(2) - Abstract
International audience; BACKGROUND: Combined effect of both prenatal and early postnatal exposure to ambient air pollution on child cognition has rarely been investigated and sensitive periods of sensitivity are unknown. This study explores the temporal relationship between pre- and postnatal exposure to PM(10), PM(2.5), NO(2) and child cognitive function. METHODS: Using validated spatiotemporally resolved exposure models, pre- and postnatal daily PM(2.5), PM(10) (satellite based, 1 km resolution) and NO(2) (chemistry-transport model, 4 km resolution) concentrations at the mother’s residence were estimated for 1271 mother-child pairs from the French EDEN and PELAGIE cohorts. Scores representative of children’s General, Verbal and Non-Verbal abilities at 5-6 years were constructed based on subscale scores from the WPPSI-III, WISC-IV or NEPSY-II batteries, using confirmatory factor analysis (CFA). Associations of both prenatal (first 35 gestational weeks) and postnatal (60 months after birth) exposure to air pollutants with child cognition were explored using Distributed Lag Non-linear Models adjusted for confounders. RESULTS: Median exposure from conception until the 60th month of life was 19.3 μg/m(3) for PM(10), 12.4 μg/m(3) for PM(2.5) and 16.9 μg/m(3) for NO(2). Increased maternal exposure to both PM(10) and PM(2.5) between the 5th and the 11th gestational weeks was related to higher General, Verbal and Non-verbal abilities among males. On the contrary, increased maternal exposure to PM(10) between the 22nd and 29th gestational weeks was associated with lower General and Non-verbal abilities among males. Similar trends were observed for PM(2.5). No significant sensitive exposure windows were detected for postnatal exposure, NO(2) or among females. DISCUSSION: These results suggest poorer cognitive development among males at 5-6 years following increased maternal exposure to PM(10) during mid-pregnancy. Apparent protective associations observed for early prenatal exposure to PM(10) and PM(2.5) are unlikely to be causal and might be due to live birth selection bias.
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- 2023
29. Effectiveness of a Therapeutic Educational Oral Health Program for Persons with Schizophrenia: A Cluster Randomized Controlled Trial and Qualitative Approach
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Denis, Frédéric, Rat, Corinne, Cros, Lucie, Bertaud-Gounot, Valerie, El-Hage, Wissam, Jonval, Lysiane, Soudry-Faure, Agnès, Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Guillaume Régnier [Rennes], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and This trial is funded by the French Ministry of Health (Direction Générale de l’Offre de Soins).
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schizophrenia ,dental education ,oral health ,therapeutic educational program ,[SDV.IB]Life Sciences [q-bio]/Bioengineering - Abstract
International audience; BACKGROUND: The oral health of people with schizophrenia (PWS) is very poor, suggesting a need for oral health promotion programmes with a high level of evidence. The aim of the EBENE study (Clinicaltrials.gov: NCT02512367) was to develop and evaluate the effectiveness of a multidisciplinary therapeutic educational programme in oral health (TEPOH) for PWS. METHODS: A multicentre cluster randomised controlled trial, with outpatient psychiatry centres as the unit of randomisation, was designed to compare the effectiveness of TEPOH (intervention group) versus standard care (control group). The trial was conducted in 26 outpatient psychiatry centres in France (14 in the intervention group, 12 in the control group). Eligible patients with a diagnosis of schizophrenia were enroled between 2016 and 2020 and followed for 6 months. The TEPOH group received a multicomponent intervention (comprising an introductory session, three educational sessions, and a debriefing session). The primary endpoint was the evaluation of periodontal disease as a community periodontal index (CPI) score ≥ 3 at Month 6. The trial was completed using a qualitative approach based on semi-structured interviews with caregivers conducted between July 2018 and December 2019. The trial was stopped early due to difficulties in recruiting patients. RESULTS: Overall, 81 patients (of 250 planned) were included, and 54 patients completed the trial: 40 in the TEPOH group and 14 in the control group. At baseline, the percentage of CPI ≥ 3 was 42.5% in the TEPOH group and 9.1% in the control group. At Month 6, the percentage of CPI ≥ 3 was 20% in the TEPOH group and 14.3% in the control group. The qualitative evaluation underlined that the professionals emphasised the "seriousness" and "assiduity" of the patients’ participation in this programme and that the TEPOH reinforced carers’ investment in oral hygiene. It also highlighted structural factors (lack of resources for professionals, lack of teeth in PWS, COVID-19 pandemic) that may have exacerbated the difficulties with enrolment and follow-up. CONCLUSIONS: The effectiveness of this TEPOH, developed for PWS as part of the EBENE study, has not been demonstrated. Certain aspects of the programme’s content and implementation need to be reconsidered. In particular, an adapted subjective measurement scale should be developed.
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- 2023
30. Prognostic impact of precipitated cardiac decompensation in symptomatic heart failure with reduced ejection fraction and severe secondary mitral regurgitation
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Mewton, Nathan, Donal, Erwan, Picard, François, Derimay, François, Grinberg, Daniel, Delphine Maucort Boulch, Delphine, Bochaton, Thomas, Piriou, Nicolas, de Lorgeril, Amélie, Samson, Géraldine, Rouleau, Frederic, Riche, Benjamin, Trochu, Jean-Noël, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Thorax [Nantes], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Funded by the French Ministry of Health and Research National Program 2012 grant number 12-027-0355 and additional funding by Abbott Vascular, and MITRA-FR ClinicalTrials.gov, NCT01920698.
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heart failure decompensation ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,guideline directed medical therapy ,reduced ejection fraction heart failure ,percutaneous mitral valve repair ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,secondary mitral regurgitation ,advanced heart failure - Abstract
International audience; BACKGROUND: Our aim was to assess the distribution of primary (with no trigger) and secondary (with a decompensation trigger) heart failure events in a severe heart failure population and their association with two-year all-cause mortality in the Mitra.Fr study. METHODS: We included 304 patients with symptomatic heart failure, and severe mitral regurgitation and guideline directed medical therapy randomized to medical therapy alone or medical therapy with percutaneous mitral valve repair. According to the follow-up, we defined three categories of events: follow-up without any heart failure event, at least one decompensation starting with a primary heart failure decompensation or starting with a precipitated secondary heart failure event. The primary outcome was 2-years all-cause mortality. RESULTS: 179 patients (59 %) had at least one heart failure decompensation within 24-months of follow-up. 129 heart failure decompensations (72%) were a first primary heart failure and 50 (28%) were a first secondary decompensation. Finally, 30 patients had both types of decompensations but these were not taken into account for the comparison of primary and secondary decompensations. Primary decompensations were 3-times more frequent than secondary decompensations, but the mean number of heart failure decompensations was similar in the "Primary heart failure group" compared to the "Secondary heart failure group": (1.94±1.39 versus 1.80±1.07 respectively; p=0.480). Compared to patients without heart failure decompensation, patients with "Only primary decompensation" or with "Only secondary decompensation" had a significantly increased risk of death (HR=4.87, 95%CI [2.86, 8.32] and 2.68 95%CI [1.64, 4.37] respectively). All-cause mortality, was not significantly different between these two type of decompensations (HR=1.82, 95%CI [0.93, 3.58]; p=0.082), but each additional heart failure recurrence was associated with a significant increase in mortality risk (HR=1.27, 95%CI [1.08; 1.50]; p=0.005). CONCLUSIONS: In heart failure with reduced ejection fraction and severe secondary mitral regurgitation patients, primary heart failure decompensations were three-times more frequent compared to precipitated decompensations with a non-significant trend in increased risk of all-cause mortality. Our results fail to support the differentiation between primary and secondary decompensations as they seem to portend the same outcome impact.
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- 2023
31. Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial
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Zuily, Stéphane, Lefèvre, Benjamin, Sanchez, Olivier, Empis de Vendin, Ombeline, de Ciancio, Guillaume, Arlet, Jean-Benoît, Khider, Lina, Terriat, Béatrice, Greigert, Hélène, Robert, Céline, Louis, Guillaume, Trinh-Duc, Albert, Rispal, Patrick, Accassat, Sandrine, Thiery, Guillaume, Montani, David, Azarian, Réza, Meneveau, Nicolas, Soudet, Simon, Le Mao, Raphaël, Maurier, François, Le Moing, Vincent, Quéré, Isabelle, Yelnik, Cécile, Lefebvre, Nicolas, Martinot, Martin, Delrue, Maxime, Benhamou, Ygal, Parent, Florence, Roy, Pierre-Marie, Presles, Emilie, Goehringer, François, Mismetti, Patrick, Bertoletti, Laurent, Rossignol, Patrick, Couturaud, Francis, Wahl, Denis, Thilly, Nathalie, Laporte, Silvy, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), F-Crin Innovte [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHR de Metz-Thionville, Centre Hospitalier Agen-Nérac, Hôpital Bicêtre, Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), Department of Cardiology, University Hospital Jean Minjoz, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), UNEOS, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lapeyronie [Montpellier] (CHU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Lille, CHU Lille, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpitaux Civils de Colmar, Service d’Hématologie Biologique [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA), CHU d'Angers [Département Urgences], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université Jean Monnet - Saint-Étienne (UJM), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service de Chirurgie Vasculaire [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre Hospitalier Princesse Grace, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Métropole., and COVI-DOSE investigators: Stéphane Zuily, Francis Couturaud, François Goehringer, Silvy Laporte, Patrick Mismetti, Emilie Presles, Patrick Rossignol, Nathalie Thilly, Denis Wahl, Thomas Lecompte, Emmanuel Oger, Marie-Antoinette Sevestre, Florence Parent, Ygal Benhamou, Pierre-Marie Roy, Tristan Gigante, Morgane Gilg, Pierre-Luc Maclot, Bénédicte Rossignol, Jonathan Udot, Hélène Bouteille, Andréa Buchmuller, Céline Peurière, El Mehdi Siaghy, Valérie Bouaziz, Charlotte Daguin, Benjamin Grosjean, Véronique Saunier, Laurence Verger, Madlyne Jacquot, Nadine Petitpain, Martin Charly, Laurent Tordella, Emilie Presles, Guillaume Baronnet, Elisabeth Baux, Athanase Benetos, Jean-Baptiste Blanvillain, Marie Conrad, Guilhem Courte, Aurélie Cravoisy-Popovic, Virginie Dufrost, Sébastien Gibot, Philippe Guerci, Laure Joly, Antoine Kimmoun, Matthieu Koszutski, Alexandrine Larue, Bruno Levy, Marie-Reine Losser, Mathieu Mattei, Lionel Nace, Emmanuel Novy, Pierre Perez, Jean-Pierre Pertek, Camille Rigaux, Alexis Sauvage, Evelyne Schvoerer, Carine Thivilier, Lev Volkov, Piotr Zieminski, Manil Benlounes, Charles Cheng, Jean-Baptiste de Fréminville, Grégoire Détriché, Emmanuel Flammarion, Guillaume Goudot, Amer Hamdan, Raphaël Hindré, Corina Manoli, Emmanuel Messas, Adrien Michon, Tristan Mirault, Jean Pastré, Marie-Aude Penet, Benjamin Planquette, Geoffroy Volle, Rémy Hamdan, Aline Laubriet-Jazayeri, Vincent Petit, Lionel Piroth, Jean Pierre Quenot, Mélissa Saccu, Damien Barraud, Zoé Cavalli, Rostane Gaci, Mathilde Andreu, Laurent Bertoletti, Andréa Buchmuller, Elodie De Magalhaes, Sophie Bulifon, Athénaïs Boucly, Nathan Ebstein, Marc Humbert, Xavier Jaïs, Mitja Jevnikar, Laurent Savale, Andrei Horia Seferian, Charlotte Colin, Timothée Ganem, Mehdi Roumila, Romain Chopard, Matthieu Besutti, Basile Mouhat, Claire Andrejak, Stéphane Dupas, Gaëlle Le Roy, Santhi Samy-Modeliar, Anne Coste, Alexandre Fauche, David Goetghebeur, Christophe Gut-Gobert, Clément Hoffmann, Baptiste Hourmant, Cécile L'hévéder, Emmanuelle Lemoigne, Olivier Nepveu, Raphaël Paret, Gaël Picart, Saïd Azerkan, Chadia Boudaa, Julien Campagne, Peter Eszto, Benoît Godbert, Jean-François Guichard, Marion Heschung, Antoine Legoff, Jacques Mariot, Pascale Martin, Magalie Mercy, Julie Perrin, Stéphane Raymond, Nathalie Vernier, Pierre Fesler, Pierrick Henneton, Cédric Mercuzot, Nathalie Pansu, Lucas Perez, Loïc Andre, Edgar Bakhache, Marie-Charlotte Chopin, Marie Gilbert, Marc Lambert, Mohammad Ryadh Pokeerbux, François Danion, Yves Hansmann, Estelle Rougier, Yvon Ruch, Dominique Stéphan, Axel Ursenbach, Isabelle Connerade, Simon Gravier, Damien Kayser, Jean-Marc Michel, Mahsa Mohseni, Waël Younes, Ruxandra Burlacu, Amanda Lopes, Stéphane Mouly, Kladoum Nassarmadji, Damien Sène, Virginie Siguret, Alain Stepanian, Cédric Annweiler, Antoine Brangier, Vincent Dubee, Samir Henni, Jeanne Hersant, Jocelyne Loison, Léa Kern, Jean-Baptiste Laine, Claire Neveux-Brecheteau, Lucia Perez, Ruben Benainous, Bénédicte Giroux-Leprieur, Marilucy Lopez-Sublet, Saïda Khaled-Jousselin, Yohann Bernard, Amélie Amiot, Jessica Breistroff, Emilie Detry, Kadidiatou Diallo, Agnès Didier, Nathalie Dumont, Julie Egensperger, Aurélie Emmerich, Nelly François, Fanny Gallo, Valérie George, Quentin Gérome, Aurélie Gutehrle, Laure Lehman, Séverine Petit, Vanessa Piard, Maximilien Saint-Gilles, Olivier Terenzi, Amélie Marquette, Hélène Mortelette, Mathilde Audry, Amélie Cransac, Marine Maillard, Anaïs Boyer, Floriana Gallo, Arielle Urbing, Imane Zahaf, Alexandra Byczko, Amina Chaalal, Georgette Berlier, Corinne Bernabe, Souad Bezzeghoud, Caroline Chaudier, Carole Chauvet, Marina Davier, Carine Labruyere, Estelle Perrin, Michaël Pierre, Claire-Annissa Chekirine, Florence Voivret, Ramdane Meftali, Ouaffa Sabri, Anaïs Beulaygue, Julie Gall, Laure Girard, Soumia Haddaoui, Scheherazade Rami, Auriane Couderc, Aude Le Breton, Marie-Line Perruche, Cindy Claudon, Ludivine Roussel, Aude Barnier, Tiphaine Blanchard, Bénédicte Le Gall, Mélanie Pelouin, Anne-Sophie Veillon, Quam Aquereburu, Charlène Delaygue, Zahoua Ait Idir, Jérémy Drugeon, Déborah Dubrulle, Rabah Tezkratt, Anne-Sophie Frantz, Julie Drouaine, Jacqueline Dubois, Magali Eyriey, Elina Haerrel, Mélinda Beaudenon, Mialy Guenet, Thibaud Lecerf, Stéphanie Marechal-Girault, Sami Rehaiem, Romain Simon, Florence Dangeul-Potier, Morgane Goulvent, Souha Fliss, Fadhila Messani, Béatrice Mizejewski, Brigitte Mugnier, Valérie Opderbeck, Brigitte Risse
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Anticoagulation ,Heparin ,[SDV]Life Sciences [q-bio] ,COVID-19 ,Venous thromboembolism - Abstract
International audience; Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients.Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707).Findings: Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034).Interpretation: In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens.
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- 2023
32. Cost-effectiveness of hypofractionated versus conventional radiotherapy in patients with intermediate-risk prostate cancer: An ancillary study of the PROstate fractionated irradiation trial – PROFIT
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Zhou, K., Renouf, M., Perrocheau, G., Magné, N., Latorzeff, I., Pommier, P., Créhange, G., Paumier, A., Bera, G., Martin, J., Catton, C., Bellanger, Martine, Supiot, S., Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Léon Bérard [Lyon], Institut Curie [Paris], CRLCC Paul Papin, Groupe Hospitalier Bretagne Sud (GHBS), University of Newcastle [Callaghan, Australia] (UoN), University of Toronto, École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), and This study received a grant from French ministry of health (Ministère des Solidarités et de la Santé, DGOS, Grant No: DGOS_2574). The funder had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
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Male ,Prostate cancer ,Cost-effectiveness analysis ,Cost-Benefit Analysis ,Prostate ,Prostatic Neoplasms ,Hematology ,Image Guided Radiation Therapy ,Intensity Modulated Radiation Therapy ,Treatment Outcome ,Oncology ,Quality of Life ,Hypofractionation ,Humans ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Radiology, Nuclear Medicine and imaging ,France ,Prospective Studies - Abstract
International audience; Purpose: To evaluate the cost-effectiveness of moderate Hypofractionated Radiotherapy (H-RT) compared to Conventional Radiotherapy (C-RT) for intermediate-risk prostate caner (PCa).Methods: A prospective randomized clinical trial including 222 patients from six French cancer centers was conducted as an ancillary study of the international PROstate Fractionated Irradiation Trial (PROFIT). We carried-out a cost-effectiveness analysis (CEA) from the payer's perspective, with a time horizon of 48 months. Patients assigned to the H-RT arm received 6000 cGy in 20 fractions over 4 weeks, or 7800 cGy in 39 fractions over 7 to 8 weeks in the C-RT arm. Patients completed quality of life (QoL) questionnaire: Expanded Prostate Cancer Index Composite (EPIC) at baseline, 24 and 48 months, which were mapped to obtain a EuroQol five-dimensional questionnaire (EQ-5D) equivalent to generate Quality Adjusted Life Years (QALY). We assessed differences in QALYs and costs between the two arms with Generalized Linear Models (GLMs). Costs, estimated in euro (€) 2020, were combined with QALYs to estimate the Incremental Cost-effectiveness ratio (ICER) with non-parametric bootstrap.Results: Total costs per patien were lower in the H-RT arm compared to the C-RT arm €3,062 (95 % CI: 2,368 to 3,754) versus €4,285 (95 % CI: 3,355 to 5,215), (p < 0.05). QALY were marginally higher in the H-RT arm, however this difference was not significant: 0.044 (95 % CI: - 0.016 to 0.099).Conclusions: Treating localized prostate cancer with moderate H-RT could reduce national health insurance spending. Adopting such a treatment with an updated reimbursement tariff would result in improving resource allocation in RT management.
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- 2022
33. Transcriptomic evidence for tumor-specific beneficial or adverse effects of TGFβ pathway inhibition on the prognosis of patients with liver cancer
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Matthis Desoteux, Betty Maillot, Kevin Bévant, Tanguy Ferlier, Raffaële Leroux, Gaëlle Angenard, Corentin Louis, Laurent Sulpice, Karim Boudjema, Cédric Coulouarn, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and The authors are supported by Inserm, Université de Rennes 1, Région Bretagne, Ministère de l'Enseignement Supérieur de la Recherche et de l'Innovation, Ligue Nationale Contre le Cancer, Ligue Contre le Cancer (CD22, CD35, CD44, CD85) (R22026NN), Fondation ARC (R21043NN), INCa and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan cancer (Noncoding RNA in cancerology: fundamental to translational) (C20014NS). This work was supported by a grant from the French Ministry of Health and the French National Cancer Institute, PRT-K20-136, CHU Rennes, CLCC Eugène Marquis, Rennes (R21095NN). BM was supported from a fellowship from Association de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique (ACHBT) and CHU Rennes.
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TGFβ ,galunisertib ,[SDV]Life Sciences [q-bio] ,hepatocellular carcinoma ,gene signature ,survival ,General Biochemistry, Genetics and Molecular Biology - Abstract
International audience; Therapeutic targeting of the transforming growth factor beta (TGFβ) pathway in cancer represents a clinical challenge since TGFβ exhibits either tumor suppressive or tumor promoting properties, depending on the tumor stage. Thus, treatment with galunisertib, a small molecule inhibitor of TGFβ receptor type 1, demonstrated clinical benefits only in subsets of patients. Due to the functional duality of TGFβ in cancer, one can hypothesize that inhibiting this pathway could result in beneficial or adverse effects depending on tumor subtypes. Here, we report distinct gene expression signatures in response to galunisertib in PLC/PRF/5 and SNU-449, two cell lines that recapitulate human hepatocellular carcinoma (HCC) with good and poor prognosis, respectively. More importantly, integrative transcriptomics using independent cohorts of patients with HCC demonstrates that galunisertib-induced transcriptional reprogramming in SNU-449 is associated with human HCC with a better clinical outcome (i.e., increased overall survival), while galunisertib-induced transcriptional reprogramming in PLC/PRF/5 is associated with human HCC with a worse clinical outcome (i.e., reduced overall survival), demonstrating that galunisertib could indeed be beneficial or detrimental depending on HCC subtypes. Collectively, our study highlights the importance of patient selection to demonstrate a clinical benefit of TGFβ pathway inhibition and identifies Serpin Family F Member 2 (SERPINF2) as a putative companion biomarker for galunisertib in HCC.
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- 2023
34. Non‐invasive diagnosis of alcohol‐related steatohepatitis in patients ongoing alcohol withdrawal based on cytokeratin 18 and transient elastography
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Arnaud Chalin, Bruno Turlin, Ahmad Ousmen, Sophie Michalak, Johannes Mueller, Sebastian Mueller, Ludivine Legros, Edouard Bardou‐Jacquet, Jean François Viel, Michel Samson, Romain Moirand, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Universität Heidelberg [Heidelberg] = Heidelberg University, and Programme Hospitalier de Recherche Clinique, French Ministry of Health, 2012
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Hepatology ,[SDV]Life Sciences [q-bio] ,Gastroenterology ,Pharmacology (medical) - Abstract
International audience; BACKGROUND AND AIMS: The diagnosis of alcoholic steatohepatitis (ASH) is based on liver biopsy, which is costly and invasive with non-negligible morbidity. The aim of this study was to evaluate the accuracy of circulating cytokeratin 18 M65 fragment (K18-M65) alone or in association with other markers for the non-invasive diagnosis of ASH in patients ongoing alcohol withdrawal. METHODS: This study examined the serum level of K18-M65 in a test cohort of 196 patients. All patients underwent liver biopsy, transient elastography (TE) and serum collection. The diagnostic accuracy of K18-M65 alone or combined with clinico-biological data was assessed and the best defined cut-offs were validated in an independent validation cohort of 58 patients. RESULTS: K18-M65 had an area under the curve (AUC) of 0.82 (test cohort) and 0.90 (validation cohort). Using two cut-off decision points, K18-M65 was able to classify 46.9% (test cohort) and 34.5% (validation cohort) of patients with 95% sensitivity or specificity. Combining K18-M65, alpha-2-macroglobulin, TE, body mass index, and age, we created a score allowing accurate diagnosis of ASH with an AUC of 0.93 (test cohort) and 0.94 (validation cohort). This new score was able to rule out or rule in the diagnosis of steatohepatitis for probability ≤0.135 or ≥0.667 respectively in more than two-thirds of patients. CONCLUSIONS: We propose a new validated non-invasive score for the diagnosis of ASH in patients ongoing alcohol withdrawal. This score can help to identify patients that may benefit from potential therapeutics or motivate them to reduce alcohol consumption.
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- 2023
35. Preoperative language rehabilitation in drug-resistant temporal lobe epilepsy (PReLang): Protocol for a randomized controlled study
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Sabadell, Véronique, Zielinski, Christelle, Baumstarck, Karine, Tardoski, Sophie, Hammam, Kahina, Bartolomei, Fabrice, Alario, F.-Xavier, Trébuchon, Agnès, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de psychologie cognitive (LPC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d'Epileptologie et de Rythmologie Cérébrale [Hôpital de la Timone, AP-HM], Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institute of Language, Communication and the Brain (ILCB), Laboratoire Parole et Langage (LPL), French Ministry of Health (REPREO, 2020, PHRIP-20-0286, commitment authorization 353625)John Bost Foundation, and ANR-16-CONV-0002,ILCB,ILCB: Institute of Language Communication and the Brain(2016)
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[SCCO]Cognitive science ,[SDV]Life Sciences [q-bio] - Abstract
Introduction: Drug-resistant epileptic patients who undergo a left anterior temporal lobectomy often experience increased naming difficulties following surgery (41% of cases). Prehabilitation, i.e., rehabilitation before surgery, could induce protective brain plasticity, likely to increase cognitive reserve, particularly for patients with high risk of postoperative cognitive decline. The efficiency of language prehabilitation on postsurgical outcomes has never been thoroughly tested. The present study is the first one testing a possible protective effect of preoperative language rehabilitation in temporal lobe epilepsy surgery.Methods and analysis: The planned study (PReLang – REPREO) is a two-year large-scale randomized controlled trial of the pre-surgical management of language processing in the context of left temporal lobe epilepsy surgery. A total of 214 subjects waiting for anterior temporal lobectomy will be randomized and assigned either to the control group —who will benefit from standard of care — or to the experimental group — who will benefit from a language prehabilitation designed to protect against post-operative language decline. Both groups will undergo the same language assessments and questionnaires before surgery, seven days after surgery, and six months far from surgery.
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- 2023
36. Impact of breast cancer care pathways and related symptoms on the return-to-work process: results from a population-based French cohort study (CONSTANCES)
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Anne-Lise Rolland, Bertrand Porro, Sofiane Kab, Céline Ribet, Yves Roquelaure, Mélanie Bertin, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), This manuscript was prepared in context of the SIRIC ILIAD program supported by a grant from the French National Cancer Institute (INCa), the French Ministry of Health, and the Institute of Health and Medical Research (Inserm), contract INCa-DGOS-Inserm_12558. The Constances cohort is supported and funded by the Caisse nationale d’assurance maladie (CNAM). The Constances Cohort Study is an 'Infrastructure nationale en Biologie et Santé' and benefits from a grant from ANR (ANR-11-INBS-0002) and from the Ministry of Research. Constances is also partly funded by MSD and L’Oréal., ANR-11-INBS-0002,CONSTANCES,La cohorte CONSTANCES - Infrastructure épidémiologique ouverte pour la recherche et la surveillance(2011), and EHESP-Irset (EHESP-Irset)
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Breast cancer ,Return to work ,Care pathways ,Sequence analysis ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Patterns - Abstract
Background Breast cancer (BC) treatments and related symptoms may affect return to work (RTW). The objective of this study was to investigate the impact of BC care pathways (timing and sequence of treatments) and related symptoms on RTW. Methods The study population included working-age women with BC who were enrolled in the French CONSTANCES cohort from 2012 to 2018. BC treatments, antidepressant/anxiolytic and antalgic drug deliveries (used as proxies of depression and pain, respectively) and statutory sick pay (used to estimate RTW and time to RTW) were assessed monthly using data from the French national healthcare system database. BC care pathways were identified with the sequence analysis method. Cox models with time-dependent covariates were used to investigate the impact of BC care pathways and related symptoms on RTW and time to RTW, after adjusting for age and socioeconomic characteristics. Results 73.2% (231/303) of women returned to work within 2 years after BC diagnosis. Five BC care pathway patterns were identified: (i) BC surgery only, (ii) BC surgery and radiotherapy, (iii) BC surgery and chemotherapy, (iv) BC surgery and chemotherapy and radiotherapy, and (v) BC surgery and long-term alternative chemotherapy/radiotherapy. The hazards ratios of non-RTW were significantly higher for women who received BC surgery and long-term alternative chemotherapy/radiotherapy and for > 55-year-old women. Time to RTW was significantly longer in women who received chemotherapy (patterns iii to v) and in women with antidepressant/anxiolytic and antalgic drug deliveries. Conclusion This study highlights the value of considering the dynamic, cumulative and temporal features of BC care pathways and related symptoms to facilitate the RTW of women with BC.
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- 2023
37. Disruption in normal correlational patterns of metabolic networks in the limbic circuit during transient global amnesia
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Shailendra Segobin, Cyrielle Renault, Fausto Viader, Francis Eustache, Anne Lise Pitel, Peggy Quinette, Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and This study was funded by a hospital-based clinical research program (identification number: ID RCB 2007-A00910-53) provided by the French Ministry of Health and Care.
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memory ,[SCCO]Cognitive science ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,PET ,Neurology ,emotion ,transient global amnesia ,metabolism ,Biological Psychiatry - Abstract
Transient global amnesia is characterized by the sudden apparition of severe episodic amnesia, mainly anterograde, associated with emotional changes. Even though the symptoms are stereotyped, cerebral mechanism underlying transient global amnesia remains unexplained and previous studies using positron emission tomography do not show any clear results or consensus on cerebral regions impacted during transient global amnesia. This study included a group of 10 transient global amnesic patients who underwent 18F-fluorodeoxyglucose positron emission tomography during the acute or recovery phase of the episode and 10 paired healthy controls. Episodic memory was evaluated with the encoding-storage-retrieval paradigm and a story recall test of the Wechsler’s memory scale and anxiety was assessed with the Spielberger scale. We used statistical parametric mapping to identify modifications of whole-brain metabolism. Regarding hypometabolism, there was no brain region systematically affected in all transient global amnesic patients and the comparison between amnesic patients and controls did not show any significant differences. To better understand the specific implication of the limbic circuit in the pathophysiology of transient global amnesia, we then conducted a correlational analysis that included regions of this network. Our findings showed that in healthy controls, regions of the limbic circuit seem to operate in a synchronized way with all regions being highly correlated to each other. On the opposite, in transient global amnesic patients, we observed a clear disruption of this normal correlational patterns between regions with the medial temporal lobe (the hippocampus, parahippocampal gyrus and amygdala) included in one cluster and the orbitofrontal cortex, anterior and posterior cingulate gyrus and thalamus gathered in the other one. Given the individual variability in the time course of transient global amnesia, the direct comparison between a group of patients and controls does not seem to favour the identification of subtle and transient alterations in regional metabolism. The involvement of an extended network, such as the limbic circuit, seems more likely to explain the symptoms of patients. Indeed, the synchronization of regions within the limbic circuit seems to be altered during transient global amnesia, which could explain the amnesia and anxiety observed in transient global amnesic patients. The present study thus deepens our understanding of the mechanisms underlying not only amnesia but also the emotional component of transient global amnesia by considering it as a disruption in the normal correlational patterns within the limbic circuit.
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- 2023
38. Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)
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Jean Reignier, Gaetan Plantefeve, Jean-Paul Mira, Laurent Argaud, Pierre Asfar, Nadia Aissaoui, Julio Badie, Nicolae-Vlad Botoc, Laurent Brisard, Hoang-Nam Bui, Delphine Chatellier, Louis Chauvelot, Alain Combes, Christophe Cracco, Michael Darmon, Vincent Das, Matthieu Debarre, Agathe Delbove, Jérôme Devaquet, Louis-Marie Dumont, Olivier Gontier, Samuel Groyer, Laurent Guérin, Bertrand Guidet, Yannick Hourmant, Samir Jaber, Fabien Lambiotte, Christophe Leroy, Philippe Letocart, Benjamin Madeux, Julien Maizel, Olivier Martinet, Frédéric Martino, Virginie Maxime, Emmanuelle Mercier, Mai-Anh Nay, Saad Nseir, Johanna Oziel, Walter Picard, Gael Piton, Jean-Pierre Quenot, Florian Reizine, Anne Renault, Jack Richecoeur, Jean-Philippe Rigaud, Francis Schneider, Daniel Silva, Michel Sirodot, Bertrand Souweine, Fabienne Tamion, Nicolas Terzi, Didier Thévenin, Guillaume Thiery, Nathalie Thieulot-Rolin, Jean-Francois Timsit, Francois Tinturier, Patrice Tirot, Thierry Vanderlinden, Isabelle Vinatier, Christophe Vinsonneau, Sebastian Voicu, Jean-Baptiste Lascarrou, Amélie Le Gouge, Damien Contou, Olivier Pajot, Paul Jaubert, Nathalie Marin, Marie Simon, Martin Cour, Satar Mortaza, Vincent Souday, Marie Lemerle, Sylvain Malfroy, Fernando Berdaguer Ferrari, Bertrand Rozec, Didier Gruson, Charline Sazio, Suzanne Champion, Florence Boissier, Anne Veinstein, Loredana Baboi, Jean-Christophe Richard, Hodane Yonis, Loïc Le Guennec, Lucie Lefevre, Juliette Chommeloux, Guillaume Hékimian, Virginie Lemiale, Eric Mariotte, Sandrine Valade, Joanna Tirolien, Yannick Fedun, Charles Cerf, Guillaume Tachon, Jérôme Roustan, Sylvie Vimeux, Michel Bonnivard, Nadia Anguel, David Osman, Karim Asehnoune, Antoine Roquilly, Fouad Belafia, Matthieu Conseil, Moussa Cisse, Bouras Chaouki, Rémi Espenel, Christine Brasse, Sébastien Ena, Arnaud Delahaye, Jeremy Castanera, Thierry Dulac, Philippe Petua, Yoann Zerbib, Clément Brault, Djillali Annane, Rania Bounab, Nicholas Heming, Thierry Boulain, Sophie Jacquier, Grégoire Muller, Raphael Favory, Sébastien Préau, Julien Poissy, Alexandre Massri, Floriane Lissonde, Hadrien Winiszewski, Thibault Vieille, Marine Jacquier, Marie Labruyère, Pascal Andreu, Jean-Marc Tadié, Laetitia Bodenes, Danièle Combaux, David Luis, Antoine Marchalot, Jean-Etienne Herbrecht, Raphaël Clere-Jehl, David Schnell, Jérôme Aboad, David Bougon, Etienne Escudier, Elisabeth Coupez, Claire Dupuis, Zoe Demailly, Louis-Marie Galerneau, Jonathan Chelly, Franck Pourcine, Ly Van Vong, Sonia Abid, Etienne De Montmollin, Romain Sonneville, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Vincent Pages, Caroline Séjourné, Imen Rahmani, Ghada Sbouj, Bruno Megarbane, Nicolas Deye, Isabelle Malissin, Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier Argenteuil (CH Argenteuil), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), CH de Saint-Malo [Broussais], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Croix-Rousse [CHU - HCL], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier d'Angoulême (CH Angoulême), Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Centre hospitalier Saint-Brieuc, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital Foch [Suresnes], Hôpital Louis Mourier - AP-HP [Colombes], Hôpitaux de Chartres [Chartres], Centre hospitalier de Montauban (CH Montauban), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Emile Roux [AP-HP], Hôpital Jacques Puel - Bourran [Rodez] (HJPB), Centre Hospitalier de Bigorre [Tarbes], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Unité de Soins Intensifs [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Hôpital Raymond Poincaré [Garches], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'interculturalité et la circulation médiatique des savoirs (CRICS (EA_3965)), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional d'Orléans (CHRO), CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Centre hospitalier de Pau, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Bourgogne (UB), Centre Hospitalier Universitaire [Rennes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier de Beauvais, Centre hospitalier de Dieppe, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier de Lens, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Intensive Care Unit, Groupe Hospitalier Sud Ile de France, 270 avenue Marc Jacquet, 77000, Melun, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Le Mans (CH Le Mans), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and French Ministry of Health.
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Pulmonary and Respiratory Medicine ,[SDV]Life Sciences [q-bio] - Abstract
Also written with the NUTRIREA-3 Trial Investigators and the Clinical Research in Intensive Care and Sepsis (CRICS-TRIGGERSEP) Group; International audience; BackgroundThe optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.MethodsThe pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2–0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0–1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.FindingsOf 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference –1·5%, 95% CI –5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0–14·0) in the low group and 9·0 days (5·0–17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p
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- 2023
39. Real-Time Detection of ESR1 Mutation in Blood by Droplet Digital PCR in the PADA-1 Trial: Feasibility and Cross-Validation with NGS
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Celine Callens, Francois-Clement Bidard, Anaïs Curto-Taribo, Olfa Trabelsi-Grati, Samia Melaabi, Suzette Delaloge, Anne-Claire Hardy-Bessard, Thomas Bachelot, Florian Clatot, Thibault De La Motte Rouge, Jean-Luc Canon, Laurent Arnould, Fabrice Andre, Sandrine Marques, Marc-Henri Stern, Jean-Yves Pierga, Anne Vincent-Salomon, Camille Benoist, Emmanuelle Jeannot, Frederique Berger, Ivan Bieche, Anne Pradines, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Centre Léon Bérard [Lyon], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Eugène Marquis (CRLCC), Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, UNICANCER, Unité de génétique et biologie des cancers (U830), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Institut Curie [Paris], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud, Pfizer, AstraZeneca, Roche, Ministère des Affaires Sociales et de la Santé, Institut National Du Cancer, INCa: PRT-K19-110, Institut Curie: INCa-DGOS-INSERM_12554, The authors declare the following competing financial interest(s): F.-C.B.: Grants from Pfizer during the conduct of the study, grants, personal fees, and nonfinancial support from Pfizer and Novartis personal fees from Lilly, Amgen, Sanofi, and Radius personal fees and nonfinancial support from Roche and AstraZeneca, grants and personal fees from Seagen, and grants from Prolynx outside the submitted work, and a pending patent on ctDNA detection by ddPCR. F.-C.B., M.-H.S., and E.J. are coholders of a patent related to ESR1 mutation detection (PCT/EP2019/056445). S.D.: Consulting Fees (e.g., advisory boards), Author, AstraZeneca, Besins, Rappta. Contracted Research, Pfizer, MSD, BMS, AstraZeneca, Orion, Sanofi, Novartis, Puma, Roche, Lilly, Daich. A.-C.H.-B.: Personal fees from AstraZeneca, Daiichi, Clovis, GSK, MSD, Novartis, Pfizer, and Roche outside the submitted work. T.B.: Consulting Fees (e.g., advisory boards), AstraZeneca, SeaGen, Roche, Novartis, Pfizer. Contracted Research, Roche, AstraZeneca, Pfizer, SeaGen. T.D.L.M.R.: Consulting Fees (e.g., advisory boards), AstraZeneca, Clovis Oncology, Eisai, MSD, Novartis, Pfizer, Roche, Sanofi, Tesaro. Contracted Research, Novartis, Pfizer, AstraZeneca. Other, AstraZeneca, MSD, Roche, Pfizer. F.A.: Grants from Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, and Lilly outside the submitted work. M.S.: Receipt of Intellectual Property Rights/Patent Holder, patent on ESR1 ddPCR. J.P.: Consulting Fees (e.g., advisory boards), Exact Sciences, AstraZeneca, Daiichi, Sankyo, Lilly, Novartis, Pfizer, Pierre Fabre, Oncology, Roche, SeaGen. Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speaker bureaus), Amgen, MSD, Novartis, Pfizer, SeaGen. Contracted Research, Servier, Roche. F.J.: Receipt of Intellectual Property Rights/Patent Holder, patent on ESR1 ddPCR. Acknowledgments, and This study was supported by a grant from the French Ministry of Health and the French National Cancer Institute (Grant PRT-K19-110) and Pfizer. The PADA-1 trial was funded by Pfizer through a grant to Unicancer. The initial development of the bESR1 assay used in the trial was supported by the Institut Curie SIRIC2 program (Grant INCa-DGOS-INSERM_12554). mut
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[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,Mutation ,Feasibility Studies ,High-Throughput Nucleotide Sequencing ,Humans ,Polymerase Chain Reaction ,Circulating Tumor DNA ,Analytical Chemistry - Abstract
International audience; The clinical actionability of circulating tumor DNA requires sensitive detection methods with a short turnaround time. In the PADA-1 phase 3 trial (NCT03079011), metastatic breast cancer patients treated with an aromatase inhibitor and palbociclib were screened every 2 months for activating ESR1 mutations in blood (bESR1mut). We report the feasibility of the droplet digital polymerase chain reaction (ddPCR) and cross-validation with next-generation sequencing (NGS). bESR1mut testing was centralized in two platforms using the same ddPCR assay. Results were reported as copies/mL of plasma and mutant allele frequency (MAF). We analyzed 200 positive ddPCR samples with an NGS assay (0.5-1% sensitivity). Overall, 12,552 blood samples were collected from 1017 patients from 83 centers. Among the 12,525 available samples with ddPCR results, 11,533 (92%) were bESR1mut-negative. A total of 267 patients newly displayed bESR1mut (26% patients/2% samples) with a median copy number of 14/mL (range: 4-1225) and a median MAF of 0.83% (0.11-35), 648 samples (20% patients/5% samples) displayed persistent bESR1mut, and 77 (
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40. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19
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Bradbury, Charlotte A., Lawler, Patrick R., Stanworth, Simon J., McVerry, Bryan J., McQuilten, Zoe, Higgins, Alisa M., Mouncey, Paul R., Al-Beidh, Farah, Rowan, Kathryn M., Berry, Lindsay R., Lorenzi, Elizabeth, Zarychanski, Ryan, Arabi, Yaseen M., Annane, Djillali, Beane, Abi, Van Bentum-Puijk, Wilma, Bhimani, Zahra, Bihari, Shailesh, Bonten, Marc J. M., Brunkhorst, Frank M., Buzgau, Adrian, Buxton, Meredith, Carrier, Marc, Cheng, Allen C., Cove, Matthew, Detry, Michelle A., Estcourt, Lise J., Fitzgerald, Mark, Girard, Timothy D., Goligher, Ewan C., Goossens, Herman, Haniffa, Rashan, Hills, Thomas, Huang, David T., Horvat, Christopher M., Hunt, Beverley J., Ichihara, Nao, Lamontagne, Francois, Leavis, Helen L., Linstrum, Kelsey M., Litton, Edward, Marshall, John C., McAuley, Daniel F., McGlothlin, Anna, McGuinness, Shay P., Middeldorp, Saskia, Montgomery, Stephanie K., Morpeth, Susan C., Murthy, Srinivas, Neal, Matthew D., Nichol, Alistair D., Parke, Rachael L., Parker, Jane C., Reyes, Luis, Saito, Hiroki, Santos, Marlene S., Saunders, Christina T., Serpa-Neto, Ary, Seymour, Christopher W., Shankar-Hari, Manu, Singh, Vanessa, Tolppa, Timo, Turgeon, Alexis F., Turner, Anne M., van de Veerdonk, Frank L., Green, Cameron, Lewis, Roger J., Angus, Derek C., McArthur, Colin J., Berry, Scott, Derde, Lennie P. G., Webb, Steve A., Gordon, Anthony C., Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Vermassen, Joris, REMAP-CAP Investigators, University of Bristol [Bristol], University Health Network, University of Toronto, University of Oxford, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Monash University [Melbourne], Imperial College London, University of Manitoba [Winnipeg], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University Medical Center [Utrecht], St. Michael's Hospital, 215522, CS-2016-16-011, RP-2015-06-18, National Institutes of Health, NIH, U.S. Department of Defense, DOD, National Institute of General Medical Sciences, NIGMS, National Institute of Neurological Disorders and Stroke, NINDS, Gordon and Betty Moore Foundation, GBMF, Medtronic, Baxter International, Medical Center, University of Pittsburgh, CancerCare Manitoba Foundation, CCMF, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD, Wellcome Trust, WT, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, LAM Therapeutics, Canadian Institutes of Health Research, IRSC: 158584, Medical Research Council, MRC, National Institute for Health and Care Research, NIHR, European Commission, EC, National Heart and Lung Institute, NHLI, Queen's University Belfast, QUB: US8962032, National Health and Medical Research Council, NHMRC: APP1101719, National Medical Research Council, NMRC, Health Research Council of New Zealand, HRC: 16/631, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Swedish Orphan Biovitrum, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support: This study was funded by the following: the Platform for European Preparedness Against (Re-)Emerging Epidemics (PREPARE) consortium of the European Union, FP7-HEALTH-2013-INNOVATION-1 (grant 602525), the Rapid European COVID-19 Emergency Research Response (RECOVER) consortium of the European Union’s Horizon 2020 Research and Innovation Programme (grant 101003589), the Australian National Health and Medical Research Council (grant APP1101719), the Health Research Council of New Zealand (grant 16/631), the Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program (grant 158584), the NIHR and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (grant CTN 2014-012), the University of Pittsburgh Medical Center (UPMC) Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (grant PHRC-20-0147), the Minderoo Foundation, and the Wellcome Trust Innovations Project (grant 215522). Dr Shankar-Hari is funded by an NIHR clinician scientist fellowship (grant CS-2016-16-011) and Dr Gordon is funded by an NIHR research professorship (grant RP-2015-06-18)., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Clinical Trials Group, the Irish Critical Care Clinical Trials Network, the UK Critical Care Research Group and the International Forum of Acute Care Trialists., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands, reported receipt of personal fees from Lilly, BMS-Pfizer, Bayer, Amgen, Novartis, Janssen, Portola, Ablynx, and Grifols. Dr Lawler reported receipt of personal fees from Novartis, CorEvitas, and Brigham and Women’s Hospital and royalties from McGraw-Hill Publishing. Dr McVerry reported receipt of grants from the National Heart, Lung, and Blood Institute and Bayer Pharmaceuticals and personal fees from Boehringer Ingelheim. Dr L. Berry reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Lorenzi reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Zarychanski reported receipt of grants from the Canadian Institutes of Health Research, LifeArc, Research Manitoba, the CancerCare Manitoba Foundation, Peter Munk Cardiac Centre, and the Thistledown Foundation and research operating support as the Lyonel G. Israels Research Chair in Hematology. Dr Bonten reported membership in international study steering committees, advisory boards, and independent data safety and monitoring committees funded by Janssen Vaccines, Merck Sharp & Dohme, AstraZeneca, Pfizer, and Sanofi Pasteur (all reimbursements to UMC Utrecht). Dr Brunkhorst reported receipt of grants from Jena University Hospital. Dr Buxton reported receipt of a gift from the Breast Cancer Research Foundation and contracts with Amgen and Eisai. Dr Carrier reported receipt of grants from BMS-Pfizer and personal fees from Bayer, Sanofi, Servier, Leo Phama, and BMS-Pfizer to his institution. Dr Cove reported receipt of grants from the National Medical Research Council and personal fees from Baxter and Medtronic. Dr Estcourt reported receipt of grants from the UK National Institute for Health Research (NIHR) and the European Union Horizon 2020 Research and Innovation Programme. Dr Haniffa reported receipt of grants from the UK Research and Innovation/Medical Research Council African Critical Care Registry Network. Dr Horvat reported receipt of grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Dr Ichihara reported being affiliated with the Department of Healthcare Quality Assessment, University of Tokyo, which is a social collaboration supported by the National Clinical Database, Johnson & Johnson, and Nipro Corporation. Dr Marshall reported receipt of personal fees from AM Pharma and Critical Care Medicine. Dr McAuley reported receipt of personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Lilly, Vir Biotechnology, Faron Pharmaceutical, and SOBI and grants from the NIHR, the Wellcome Trust, Innovate UK, the UK Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, in addition, Dr McAuley had a Queen’s University Belfast patent for novel treatment for inflammatory disease (US8962032), was co-director of research at the Intensive Care Society until June 2021, and was director of the Efficacy and Mechanisms Evaluation Program for the UK Medical Research Council/NIHR. Dr Middeldorp reported receipt of personal fees from Daiichi Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Portola/Alexion, AbbVie, BMS-Pfizer, Sanofi, and Viatris, all paid to his institution, and grants from Daiichi Sankyo, Bayer, Pfizer, and Boehringer Ingelheim. Dr Neal reported equity in Haima Therapeutics, receipt of personal fees from Janssen Pharma and Haemonetics, and receipt of grants from Instrumentation Laboratory, the National Institutes of Health, and the Department of Defense. Dr Nichol reported receipt of personal fees from AM Pharma, paid to his university, and grants from Baxter. Dr Parke reported receipt of grants from Fisher and Paykel Healthcare NZ. Dr Serpa-Neto reported receipt of personal fees from Drager and Endpoint Health. Dr Seymour reported receipt of grants from the Gordon and Betty Moore Foundation and the National Institutes of Health/National Institute of General Medical Sciences. Dr Lewis reported being senior medical scientist at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr S. Berry reported being an employee with an ownership role at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Derde reported being a coordinating committee member for the European Clinical Research Alliance on Infectious Diseases, a member of the Dutch Intensivists Task Force on Acute Infectious Threats, a member of the International Scientific Advisory Board for Sepsis Canada, and a member of the Dutch Academy of Sciences’ Pandemic Preparedness Plan committee. Dr Gordon reported receipt of personal fees from 30 Respiratory, paid to his institution. No other disclosures were reported., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), Investigators, REMAP-CAP Writing Committee for the REMAP-CAP, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, and Intensive Care Medicine
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Adult ,Male ,Platelet Aggregation Inhibitors/adverse effects ,Critical Illness ,[SDV]Life Sciences [q-bio] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Hemorrhage ,Aspirin/adverse effects ,Hemorrhage/chemically induced ,INFECTION ,Humans ,COAGULOPATHY ,Aspirin ,Anticoagulants ,COVID-19 ,Bayes Theorem ,Venous Thromboembolism ,General Medicine ,Middle Aged ,Respiration, Artificial ,COVID-19 Drug Treatment ,Critical Illness/mortality ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Purinergic P2Y Receptor Antagonists/adverse effects ,Purinergic P2Y Receptor Antagonists ,COVID-19/complications ,Female ,Human medicine ,Anticoagulants/adverse effects ,Platelet Aggregation Inhibitors ,Venous Thromboembolism/drug therapy - Abstract
Contains fulltext : 248713.pdf (Publisher’s version ) (Closed access) IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). CONCLUSIONS AND RELEVANCE: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.
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41. Factors associated with acute mesenteric ischemia among critically ill ventilated patients with shock: a post hoc analysis of the NUTRIREA2 trial
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Piton, Gaël, Le Gouge, Amélie, Boisramé-Helms, Julie, Anguel, Nadia, Argaud, Laurent, Asfar, Pierre, Botoc, Vlad, Bretagnol, Anne, Brisard, Laurent, Bui, Hoang-Nam, Canet, Emmanuel, Chatelier, Delphine, Chauvelot, Louis, Darmon, Michael, Das, Vincent, Devaquet, Jérôme, Djibré, Michel, Ganster, Frédérique, Garrouste-Orgeas, Maité, Gaudry, Stéphane, Gontier, Olivier, Groyer, Samuel, Guidet, Bertrand, Herbrecht, Jean-Etienne, Hourmant, Yannick, Lacherade, Jean-Claude, Letocart, Philippe, Martino, Frédéric, Maxime, Virginie, Mercier, Emmanuelle, Mira, Jean-Paul, Nseir, Saad, Quenot, Jean-Pierre, Richecoeur, Jack, Rigaud, Jean-Philippe, Roux, Damien, Schnell, David, Schwebel, Carole, Silva, Daniel, Sirodot, Michel, Souweine, Bertrand, Thieulot-Rolin, Nathalie, Tinturier, François, Tirot, Patrice, Thévenin, Didier, Thiéry, Guillaume, Lascarrou, Jean-Baptiste, Reignier, Jean, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional d'Orléans (CHRO), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hospices Civils de Lyon (HCL), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Hôpital Foch [Suresnes], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital de Hautepierre [Strasbourg], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier de Dieppe, Hôpital Louis Mourier - AP-HP [Colombes], Centre Hospitalier d'Angoulême (CH Angoulême), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier de Lens, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Ministère des Affaires Sociales et de la Santé: PHRCN-12–0184, and The NUTRIREA2 study was supported by a grant from the French Ministry of Health, PHRCN-12–0184.
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Acute mesenteric ischemia ,[SDV]Life Sciences [q-bio] ,Shock ,cardiovascular diseases ,Critically ill ,Enteral nutrition ,Parenteral nutrition ,Critical Care and Intensive Care Medicine - Abstract
International audience; Purpose: Acute mesenteric ischemia (AMI) is a rare, but life-threatening condition occurring among critically ill patients. Several factors have been associated with AMI, but the causal link is debated, most studies being retrospective. Among these factors, enteral nutrition (EN) could be associated with AMI, in particular among patients with shock. We aimed to study the factors independently associated with AMI in a post hoc analysis of the NUTRIREA-2 trial including 2410 critically ill ventilated patients with shock, randomly assigned to receive EN or parenteral nutrition (PN). Methods: Post hoc analysis of the NUTRIREA-2 trial was conducted. Ventilated adults with shock were randomly assigned to receive EN or PN. AMI was assessed by computed tomography, endoscopy, or laparotomy. Factors associated with AMI were studied by univariate and multivariate analysis. Results: 2410 patients from 44 French intensive care units (ICUs) were included in the study: 1202 patients in the enteral group and 1208 patients in the parenteral group. The median age was 67 [58–76] years, with 67% men, a SAPS II score of 59 [46–74], and a medical cause for ICU admission in 92.7%. AMI was diagnosed among 24 (1%) patients, mainly by computed tomography (79%) or endoscopy (38%). The mechanism of AMI was non-occlusive mesenteric ischemia (n = 12), occlusive (n = 4), and indeterminate (n = 8). The median duration between inclusion in the trial and AMI diagnosis was 4 [1–11] days. Patients with AMI were older, had a higher SAPS II score at ICU admission, had higher plasma lactate, creatinine, and ASAT concentrations and lower hemoglobin concentration, had more frequently EN, dobutamine, and CVVHDF at inclusion, developed more frequently bacteremia during ICU stay, and had higher 28-day and 90-day mortality rates compared with patients without AMI. By multivariate analysis, AMI was independently associated with EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin concentration ≤ 10.9 g/dL. Conclusion: Among critically ill ventilated patients with shock, EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin ≤ 10.9 g/dL were independently associated with AMI. Among critically ill ventilated patients requiring vasopressors, EN should be delayed or introduced cautiously in case of low cardiac output requiring dobutamine and/or in case of multiple organ failure with high SAPS II score.
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42. Infant feeding practices associated with adiposity peak and rebound in the EDEN mother–child cohort
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Aurore Camier, Aminata H. Cissé, Sandrine Lioret, Jonathan Y. Bernard, Marie Aline Charles, Barbara Heude, Blandine de Lauzon-Guillain, de Lauzon-Guillain, Blandine, Influence de l'alimentation infantile sur la croissance et le développement de l'enfant - - InfaDiet2019 - ANR-19-CE36-0008 - AAPG2019 - VALID, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), The EDEN study is supported by the Fondation pour la Recherche Médicale (FRM), French Ministry of Research: Federative Research Institutes and Cohort Program, INSERM Human Nutrition National Research Program, and Diabetes National Research Program (by a collaboration with the French Association of Diabetic Patients [AFD]), French Ministry of Health, French Agency for Environment Security (AFSSET), French National Institute for Population Health Surveillance (InVS), Paris‐Sud University, French National Institute for Health Education (INPES), Nestlé, Mutuelle Générale de l'Education Nationale (MGEN), French‐speaking Association for the Study of Diabetes and Metabolism (ALFEDIAM), National Agency for Research (ANR non‐thematic programme), and National Institute for Research in Public Health (IRESP: TGIR 2008 cohort in health programme).The study was funded by an ANR grant (InfaDiet project, grant no.: ANR-19-CE36-0008).This research benefited from the assistance of the funding partners of the IReSP within the framework of the 2016 General call for projects - Prevention topic (HEUDE-AAP16-PREV-24)., and ANR-19-CE36-0008,InfaDiet,Influence de l'alimentation infantile sur la croissance et le développement de l'enfant(2019)
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Male ,Nutrition and Dietetics ,infant feeding ,breastfeeding ,Endocrinology, Diabetes and Metabolism ,Infant, Newborn ,Infant ,Medicine (miscellaneous) ,Mother-Child Relations ,Body Mass Index ,Cohort Studies ,BMI ,Breast Feeding ,adiposity rebound ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Humans ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,early growth ,Obesity ,Adiposity - Abstract
International audience; Background/ObjectiveHigh magnitude of adiposity peak and early adiposity rebound are early risk markers of later obesity. Infant diet represents one of the main modifiable determinants of early growth. This study aimed to investigate the association between infant feeding practices and age and magnitude of adiposity peak and rebound.Subjects/MethodsAnalyses were based on data from the French EDEN mother–child cohort. Data on breastfeeding and complementary feeding were collected at birth and 4, 8 and 12 months. From clinical examinations and measurements collected in the child’s health booklet up to 12 years, individual growth curves were modeled, and ages and magnitudes of adiposity peak and rebound were estimated. Associations between infant feeding practices and growth were investigated by multivariable linear regression in children after testing a child-sex interaction.ResultsIn the studied population (n=1 225), adiposity peak occurred at a mean of 9.9 ± 2 months and adiposity rebound at 5.5 ± 1.4 years. Associations between infant feeding practices and adiposity peak or rebound were moderated by child sex. For girls, each additional month of breastfeeding was related to a 2-day increase in the age at adiposity peak (p
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43. Metabolic Syndrome and the Risk of Preclinical Heart Failure: Insights after 17 Years of Follow-Up from the STANISLAS Cohort
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Abhinav Sharma, Amir Razaghizad, João Pedro Ferreira, Jean-Loup Machu, Erwan Bozec, Nicolas Girerd, Patrick Rossignol, Faiez Zannad, McGill University Health Center [Montreal] (MUHC), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), McGill University = Université McGill [Montréal, Canada], Universidade do Porto = University of Porto, The STANISLAS study is sponsored by Nancy CHRU. This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013,' by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program FIGHT-HF (reference: ANR-15-RHU-0004), and by the French PIA project 'Lorraine Université d’Excellence,' reference ANR-15-IDEX-04-LUE. It is also supported by the European Fibro-Targets Project (Grant agreement No. SP7#602904), European HOMAGE project (Grant agreement No. Heart 'Omics' in Ageing, 7th Framework Program Grant # 305,507), the MEDIA project (Européen 'Cooperation'—Theme 'Health'/FP7-HEALTH-2010-single-stage (reference: 261409), FOCUS-MR (reference: ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02), and the Fondation de Recherche en Hypertension Artérielle., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016), European Project: SP7#602904, European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), and European Project: 261409,EU FP 7 MEDIA project
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[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Preclinical heart failure ,Heart failure ,Pharmacology (medical) ,Cardiology and Cardiovascular Medicine ,Metabolic syndrome - Abstract
Background: We used data from people initially free of clinical cardiovascular disease to evaluate the association between metabolic syndrome (MS) and incident preclinical heart failure (pHF). Methods and Results: STANISLAS was a familial, single-center, longitudinal prospective cohort study composed of 1,006 families from Nancy, France (median follow-up, 17 years [1993–2016]). Age- and sex-adjusted logistic regression and inverse probability weighting models were used to evaluate the association between MS and pHF, which was defined by diastolic dysfunction, atrial enlargement, ventricular hypertrophy, or elevated natriuretic peptides. Among 944 people who were adults at the first and final visit, those with baseline MS were more likely to be older (63 vs. 61 vs. 59 years of age) and male (73% vs. 55% vs. 45%) compared to people who developed incident MS and people who had no baseline MS, respectively. Furthermore, compared to people without baseline MS, the risk of pHF was numerically larger among people with baseline MS (adjusted odds ratio [aOR] 2.27, 95% CI: 1.07–4.81) and people who developed incident MS (aOR 1.56, 95% CI: 1.00–2.43). Concerning the metabolic determinants of MS, the risk of pHF was most elevated in people with baseline hypertension (aOR 3.19, 95% CI: 1.80–5.63) and elevated waist circumference (aOR 2.59, 95% CI: 1.47–4.57). Conclusion: Overall, HF is an important public health concern given the high risk of mortality when patients with MS or elevated fasting glucose become established with the disease. Early aggressive lifestyle modification and medical intervention among patients free of cardiovascular disease with an obese-hypertensive phenotype may be warranted to prevent HF development.
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- 2022
44. Caregivers in anorexia nervosa: is grief underlying parental burden?
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Duclos, Jeanne, Piva, Giulia, Riquin, Élise, Lalanne, Christophe, Meilleur, Dominique, Blondin, Soline, Cook-Darzens, Solange, Godart, Nathalie T., Berthoz, Sylvie, Mattar, Lama E., Roux, Hélène Marie, Thiébaud, Marie R., Vibert, Sarah, Hubert, Tamara, Courty, Annaig, Ringuenet, Damien, Benoit, Jean Pierre, Blanchet, Corinne, Moro, Marie Rose, Bignami, Laura, Nordon, Clémentine, Rouillon, Frederick, Cook, Solange, Doyen, Catherine M., Mouren, Marie Christine, Gerardin, Priscille, Lebecq, Sylvie, Podlipski, Marc Antoine, Gayet, Claire, Lasfar, Malaïka, Delorme, Marc, Pommereau, Xavier, Bioulac, Stéphanie, Bouvard, Manuel Pierre, Carrere, Jennifer, Doncieux, Karine, Faucher, Sophie, Fayollet, Catherine, Prexl, Amélie, Billard, Stéphane, Lang, François, Mourier-Soleillant, Virginie, Greiner, Régine, Gay, Aurélia, Carrot, Guy, Lambert, Sylvain, Rousselet, Morgane, Placé, Ludovic, Venisse, Jean Luc, Bronnec, Marie Grall, Falissard, Bruno, Genolini, Christophe M., Hassler, Christine, Tréluyer, Jean Marc, Chacornac, Olivier, Delattre, Maryline, Moulopo, Nellie, Turuban, Christelle, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint Vincent de Paul de Lille, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Centre Hospitalier le Vinatier [Bron], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Paris Cité (UPCité), Université de Montréal (UdeM), Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Agence Nationale de la Recherche, ANR, Institut National de la Santé et de la Recherche Médicale, Inserm, Fondation de France, Ministère des Affaires Sociales et de la Santé, No funding was received to assist with the preparation of this manuscript. The EVHAN study was supported by grants from the French Ministry of Health (PHRCN 2007, 2011 AOM11197, and ANR Jeune chercheur) and from CNAM-TS, Fondation de France, Fondation MGEN, EHESP, AP-HP, CIFRE, and Contrats d’interface INSERM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Parents ,Psychiatry and Mental health ,Clinical Psychology ,Living grief ,[SCCO.PSYC]Cognitive science/Psychology ,Caregiving ,Anorexia nervosa ,Burden ,Gender role - Abstract
Purpose Anorexia Nervosa (AN) is a severe chronic disorder and parents’ experience of caregiving is usually marked by emotional distress and burden. Severe chronic psychiatric disorders are known to be linked with the concept of grief. Grief has not been investigated in AN. The aim of this study was to explore parents’ and adolescents’ characteristics that may be related to parental burden and grief in AN, and the link between these two dimensions. Methods Eighty mothers, 55 fathers and their adolescents (N = 84) hospitalized for AN participated in this study. Evaluations of clinical characteristics of the adolescent’s illness were completed, as well as self-evaluations of adolescent and parental emotional distress (anxiety, depression, alexithymia). Levels of parental burden were evaluated with the Experience of Caregiving Inventory and levels of parental grief with the Mental Illness Version of the Texas Revised Inventory of Grief. Results Main findings indicated that the burden was higher in parents of adolescents with a more severe AN; fathers’ burden was also significantly and positively related to their own level of anxiety. Parental grief was higher when adolescents’ clinical state was more severe. Paternal grief was related to higher anxiety and depression, while maternal grief was correlated to higher alexithymia and depression. Paternal burden was explained by the father’s anxiety and grief, maternal burden by the mother’s grief and her child’s clinical state. Conclusion Parents of adolescents suffering from AN showed high levels of burden, emotional distress and grief. These inter-related experiences should be specific targets for intervention aimed at supporting parents. Our results support the extensive literature on the need to assist fathers and mothers in their caregiving role. This in turn may improve both their mental health and their abilities as caregivers of their suffering child. Level of evidence Level III: Evidence obtained from cohort or case-control analytic studies.
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- 2023
45. Transanal irrigation is a better choice for bowel dysfunction in adults with spina bifida: a randomized controlled trial
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Charlène Brochard, Magali Jezequel, Anne Blanchard‐Dauphin, Jacques Kerdraon, Brigitte Perrouin‐Verbe, Anne‐Marie Leroi, Jean Michel Reymann, Benoît Peyronnet, Jeff Morçet, Laurent Siproudhis, CHU Pontchaillou [Rennes], The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), CHU Lille, Centre Mutualiste de Kerpape, Ploemeur, Centre hospitalier universitaire de Nantes (CHU Nantes), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service des Maladies de l'Appareil Digestif [CHU Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and French Ministry of Health. Grant Number: 2013-A01520-45
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transanal irrigation ,faecal incontinence ,[SDV]Life Sciences [q-bio] ,Gastroenterology ,bowel dysfunction ,conservative treatment ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Spina bifida ,randomised controlled trial - Abstract
International audience; Aim: To compare transanal irrigation with conservative bowel management for the treatment of bowel dysfunction in Spina bifida (SB) patients.Methods: Patients with SB and bowel dysfunction were randomly assigned to receive either transanal irrigation or conservative bowel management. The effectiveness of the treatment was defined as a decrease of 4 points in the neurogenic bowel dysfunction (NBD) score at week 10. Data on incontinence (Cleveland scores; Jorge-Wexner [JW]) and constipation (Knowles-Eccersley-Scott Symptom Constipation Score [KESS]) were recorded at 10 and 24 weeks after inclusion. Data were analysed on an intention-to-treat basis.Results: A total of 34 patients were randomised: 16 patients to conservative bowel management and 18 patients to transanal irrigation. A total of 19/31 (61%) patients improved at week 10, 13 (76%) in the transanal irrigation group versus six (43%) in the conservative group (p = 0.056). In the irrigation group, the decrease in NBD score was -6.9 (-9.9 to -4.02) versus -1.9 (-6.5 to -2.8) in the conservative group (p = 0.049 in univariate and p = 0.004 in multivariate analysis). The NBD, Cleveland (JW and KESS) and Rosenberg scores were significantly lower in the transanal irrigation group than in the conservative bowel management group at week 10.Conclusions: This prospective, randomised, controlled, multicentre study in adult patients with SB suggests that transanal irrigation may be more effective than conservative bowel management.
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- 2023
46. Criteria for preclinical models of cholangiocarcinoma:scientific and medical relevance
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Calvisi, Diego, Boulter, Luke, Vaquero, Javier, Saborowski, Anna, Fabris, Luca, Rodrigues, Pedro, Coulouarn, Cédric, Castro, Rui, Segatto, Oreste, Raggi, Chiara, van der Laan, Luc, Carpino, Guido, Goeppert, Benjamin, Roessler, Stephanie, Kendall, Timothy, Evert, Matthias, Gonzalez-Sanchez, Ester, Valle, Juan, Vogel, Arndt, Bridgewater, John, Borad, Mitesh, Gores, Gregory, Roberts, Lewis, Marin, Jose, Andersen, Jesper, Alvaro, Domenico, Forner, Alejandro, Banales, Jesus, Cardinale, Vincenzo, Macias, Rocio, Vicent, Silve, Chen, Xin, Braconi, Chiara, Verstegen, Monique, Fouassier, Laura, Scheiter, Alexander, Selaru, Florin, Evert, Katja, Utpatel, Kirsten, Broutier, Laura, Cadamuro, Massimiliano, Huch, Meritxell, Goldin, Robert, Gradilone, Sergio, Saito, Yoshimasa, University of Regensburg, University of Edinburgh, Instituto de Salud Carlos III [Madrid] (ISC), Hannover Medical School [Hannover] (MHH), Yale School of Medicine [New Haven, Connecticut] (YSM), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Universidade de Lisboa, Università degli Studi di Firenze = University of Florence (UniFI), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Università degli Studi di Roma 'Foro Italico', Heidelberg University Hospital [Heidelberg], University of Barcelona, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], University of Manchester [Manchester], University College of London [London] (UCL), Mayo Clinic, Mayo Clinic [Rochester], Universidad de Salamanca, University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Glasgow, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), The authors thank the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and the European H2020 COST Action CA18122. The authors also acknowledge the valuable contributions of the external advisory panel. C.C. is supported by Inserm, Université de Rennes 1 and by a grant from the French Ministry of Health and the French National Cancer Institute (PRT-K20-136), CHU Rennes, CLCC Eugène Marquis, Rennes. M.M.A.V. and L.J.W.v.d.L. are supported by Medical Delta Regenerative Medicine 4D (Generating complex tissues with stem cells and printing technology) and TKI-LSH grant EMC-LSH19002. S.R. is supported by the German Research Foundation (DFG, project no. 314905040 and no. 493697503) and by German Cancer Aid (Deutsche Krebshilfe, project no. 70113922). S.V. is supported by Ministerio de Ciencia, Innovación y Universidades, Convocatoria 2019 para incentivar la Incorporación Estable de Doctores (IED2019-001007-I), by FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación (PID2020‐116344‐RB‐100) and by the Government of Navarra-Health Research Department (58, and 2018). J.V. is funded by Ministerio de Ciencia e Innovación, part of Agencia Estatal de Investigación (AEI), through the Retos Investigación grant number PID2019-108651RJ-I00/DOI 10.13039/501100011033. The authors thank CERCA Programme/Generalitat de Catalunya for institutional support. R.I.R.M. and J.J.G.M. are supported by Instituto de Salud Carlos III, Spain (PI20/00189, PI19/00819) co-funded by the European Union. L. Fouassier belongs to a team supported by the Fondation pour la Recherche Médicale (Equipe FRM 2020 no. EQU202003010517) and is supported by Inserm and Sorbonne Université, INCa and ITMO Cancer of Aviesan within the framework of the 2021–2030 Cancer Control Strategy, on funds administered by Inserm.
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Hepatology ,[SDV]Life Sciences [q-bio] ,Gastroenterology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology - Abstract
International audience; Cholangiocarcinoma (CCA) is a rare malignancy that develops at any point along the biliary tree. CCA has a poor prognosis, its clinical management remains challenging, and effective treatments are lacking. Therefore, preclinical research is of pivotal importance and necessary to acquire a deeper understanding of CCA and improve therapeutic outcomes. Preclinical research involves developing and managing complementary experimental models, from in vitro assays using primary cells or cell lines cultured in 2D or 3D to in vivo models with engrafted material, chemically induced CCA or genetically engineered models. All are valuable tools with well-defined advantages and limitations. The choice of a preclinical model is guided by the question(s) to be addressed; ideally, results should be recapitulated in independent approaches. In this Consensus Statement, a task force of 45 experts in CCA molecular and cellular biology and clinicians, including pathologists, from ten countries provides recommendations on the minimal criteria for preclinical models to provide a uniform approach. These recommendations are based on two rounds of questionnaires completed by 35 (first round) and 45 (second round) experts to reach a consensus with 13 statements. An agreement was defined when at least 90% of the participants voting anonymously agreed with a statement. The ultimate goal was to transfer basic laboratory research to the clinics through increased disease understanding and to develop clinical biomarkers and innovative therapies for patients with CCA.
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- 2023
47. Prevalence of Post-Acute COVID-19 Symptoms Twelve Months after Hospitalisation in Participants Retained in Follow-up: Analyses Stratified by Gender from a Large Prospective Cohort
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Ghosn, Jade, Bachelet, Delphine, Livrozet, Marine, Cervantes-Gonzalez, Minerva, Poissy, Julien, Goehringer, François, Gandonniere, Charlotte Salmon, Maillet, Mylène, Bani-Sadr, Firouzé, Martin-Blondel, Guillaume, Tattevin, Pierre, Launay, Odile, Surgers, Laure, Dudoignon, Emmanuel, Liegeon, Geoffroy, Zucman, David, Joseph, Cédric, Senneville, Eric, Yelnik, Cécile, Roger, Pierre-Marie, Faure, Karine, Gousseff, Marie, Cabié, André, Duval, Xavier, Chirouze, Catherine, Laouénan, Cedric, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Foch [Suresnes], Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Gustave Dron [Tourcoing], European Atherosclerosis Society [Göteborg, Sweden] (EAS), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU de la Martinique [Fort de France], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), The French COVID cohort is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium, by a grant of the French Ministry of Health (PHRC n°20-0424), and by the ORCHESTRA project which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement N°101016167. The funders had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication., DESSAIVRE, Louise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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Emerging infectious diseases ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Moderate to severe COVID-19 ,SARS-CoV-2 ,Cohort ,Post-acute COVID-19 symptoms ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Objectives - Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. Methods - Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. Results - We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale
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- 2023
48. Striking differences in weight gain after cART initiation depending on early or advanced presentation: Results from the ANRS CO4 FHDH cohort
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Sophie Grabar, Valérie Potard, Lionel Piroth, Sophie Abgrall, Louis Bernard, Clotilde Allavena, Fabienne Caby, Pierre de Truchis, Claudine Duvivier, Patricia Enel, Christine Katlama, Marie-Aude Khuong, Odile Launay, Sophie Matheron, Giovanna Melica, Hugues Melliez, Jean-Luc Meynard, Juliette Pavie, Laurence Slama, Sylvie Bregigeon, Pierre Tattevin, Jacqueline Capeau, Dominique Costagliola, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Victor Dupouy, Hôpital Raymond Poincaré [Garches], Université Paris-Saclay, CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), CHU Pitié-Salpêtrière [AP-HP], Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Hôpital Cochin [AP-HP], CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Henri Mondor, Hôpital de Riaumont [Lievin], Hôpital Hôtel-Dieu [Paris], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], The ANRS CO4 FHDH is supported by the ANRS-MIE (Agence Nationale de Recherche sur le Sida et les hépatites virales-Maladies Infectieuse Emergentes), INSERM (Institut National de la Santé et de la Recherche Médicale) and the French Ministry of Health. The funders had no role in the study design, data collection, data analysis and interpretation, or writing of the report., Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Pasteur [Paris] (IP), CHU Henri Mondor, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and GRABAR, SOPHIE
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Pharmacology ,Microbiology (medical) ,Infectious Diseases ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Pharmacology (medical) - Abstract
BackgroundMany studies have reported weight gain in ART-naive people living with HIV (PWH) initiating an integrase strand-transfer inhibitor-based regimen. We studied the impact of early or advanced presentation and that of individual drugs in PWH initiating combined ART (cART) between 2012 and 2018.MethodsFrom the French Hospital Database HIV cohort, we assessed factors associated with a weight gain ≥10%, weight change after cART initiation or BMI increase ≥5 kg/m2 up to 30 months. The analyses were conducted overall, and among PWH with early (primary infection or CD4 >350/mm3 and viral load ResultsAt 30 months, 34.5% (95% CI: 33.5–35.6) of the 12 773 PWH had a weight gain ≥10%, with 20.9% (95% CI: 19.6–22.2) among the 5794 with early presentation and 63.1% (95% CI: 60.9–65.3) among the 3106 with advanced presentation. Weight gain was 2.8 kg (95% CI: 2.0–3.7) for those with early presentation and 9.7 kg (95% CI: 8.4–11.1) for those with advanced presentation. Most weight gain occurred in the first 12 months. Underweight and obese PWH were at significantly higher risk of a BMI increase ≥5 kg/m2 than normal-weight PWH. Results differed within classes and by outcome. Raltegravir and dolutegravir were consistently associated with greater weight gain than the other third agents. Tenofovir alafenamide was also associated with higher weight gain than tenofovir disoproxil or abacavir.ConclusionsAfter initiating cART, PWH with early presentation exhibited a small weight gain, whereas it was large among those with advanced presentation. The choice of ART should account for the risk of weight gain, especially for PWH who present with advanced disease and/or are obese.
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- 2023
49. Maternal Diet Quality during Pregnancy and Allergic and Respiratory Multimorbidity Clusters in Children from the EDEN Mother–Child Cohort
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Rosalie Delvert, Manel Ghozal, Karine Adel-Patient, Manik Kadawathagedara, Barbara Heude, Marie-Aline Charles, Isabella Annesi-Maesano, Muriel Tafflet, Bénédicte Leynaert, Raphaëlle Varraso, Blandine de Lauzon-Guillain, Annabelle Bédard, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris Cité (UPCité), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de Prévention et d'Éducation pour la Santé, INPES, Agence Nationale de la Recherche, ANR: ANR-19-CE36-0008, Institut National de la Santé et de la Recherche Médicale, Inserm, Fondation pour la Recherche Médicale, FRM, Ministère des Affaires Sociales et de la Santé, Université Paris-Sud, Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, AFSSET, Mutuelle Générale de l'Education Nationale, MGEN, Institut de Veille Sanitaire, InVS, Part of this study was included in the InfaDiet project, funded by a grant from the French National Research Agency (ANR-19-CE36-0008). The EDEN study is supported by Fondation pour la Recherche Médicale (FRM), French Ministry of Research: Federative Research Institutes and Cohort Program, INSERM Human Nutrition National Research Program, and Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Ministry of Health, French Agency for Environment Security (AFSSET), French National Institute for Population Health Surveillance (InVS), Paris-Sud University, French National Institute for Health Education (INPES), Nestlé, Mutuelle Générale de l’Education Nationale (MGEN), French-speaking Association for the Study of Diabetes and Metabolism (ALFEDIAM), National Agency for Research (ANR non-thematic programme), and National Institute for Research in Public Health (IRESP: TGIR 2008 cohort in health programme). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript., and ANR-19-CE36-0008,InfaDiet,Influence de l'alimentation infantile sur la croissance et le développement de l'enfant(2019)
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maternal diet ,asthma and allergic diseases ,children ,cluster analysis ,birth cohort ,Nutrition and Dietetics ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Food Science - Abstract
We investigated the associations between maternal diet quality and allergic and respiratory diseases in children. Analyses were based on 1316 mother–child pairs from the EDEN mother–child cohort. Maternal diet quality during pregnancy was assessed through a food-based score (the Diet Quality), a nutrient-based score (the PANDiet), and the adherence to guidelines for main food groups. Clusters of allergic and respiratory multimorbidity clusters up to 8 years were identified using Latent Class Analysis. Associations were assessed by adjusted multinomial logistic regressions. Four clusters were identified for children: “asymptomatic” (67%, reference group), “asthma only” (14%), “allergies without asthma” (12%), “multi-allergic” (7%). These clusters were not associated with mother diet quality assessed by both scores. Children from mothers consuming legumes once a month or less were at higher risk of belonging to the “multi-allergic” cluster (odds ratio (OR) (95% confidence interval (95%CI)) = 1.60 (1.01;2.54)). No association was found with other food groups or other clusters. In our study, allergic and respiratory multimorbidity in children was described with four distinct clusters. Our results suggest an interest in legumes consumption in the prevention of allergic diseases but need to be confirmed in larger cohorts and randomized control trials.
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- 2023
50. Ensuring quality control in a COVID-19 clinical trial during the pandemic: The experience of the Inserm C20–15 DisCoVeRy study
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Fougerou-Leurent, Claire, Delmas, Christelle, Saillard, Juliette, Dumousseaux, Marina, Ferrane, Assia, Mercier, Noémie, Terzic, Vida, Le Mestre, Soizic, Dechanet, Aline, Belhadi, Drifa, Metois, Annabelle, Burdet, Charles, Mentré, France, Noret, Marion, Diallo, Alpha, Petrov‐sanchez, Ventzislava, Couffin-Cadiergues, Sandrine, Hites, Maya, Ader, Florence, Espérou, Hélène, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut de Santé Publique, Université de Médecine Carol Davila, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Réseau national de recherche clinique en infectiologie (RENARCI), Université libre de Bruxelles (ULB), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The DisCoVeRy study received funding from European Union Commission (EU-Response, Grant 101015736), French Ministry of Health (PHRC-20-0351), DIM One Health Île-de-France (R20117HD), REACTing, Fonds Erasme-COVID-ULB, and Belgian Health Care Knowledge Centre (KCE), AGMT GmbH, FEDER 'European Regional Development Fund', Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Remdesivir was provided free of charge by Gilead.
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Pandemic crisis ,Clinical trials ,Monitoring ,[SDV]Life Sciences [q-bio] ,Quality control ,Sponsoring - Abstract
International audience; Setting: Health measures taken during the pandemic deeply modified the clinical research practices. At the same time, the demand for the results of the COVID-19 trials was urgent. Thus, the objective of this article is to share Inserm's experience in ensuring quality control in clinical trials in this challenging context. Objectives: DisCoVeRy is a phase III randomized study that aimed at evaluating the safety and efficacy of 4 therapeutic strategies in hospitalized COVID-19 adult patients. Between March, 22nd 2020 and January, 20th 2021, 1309 patients were included. In order to guarantee the best quality of data, the Sponsor had to adapt to the current sanitary measures and to their impact on clinical research activity, notably by adapting Monitoring Plan objectives, involving the research departments of the participating hospitals and a network of clinical research assistants (CRAs). Results: Overall, 97 CRAs were involved and performed 909 monitoring visits. The monitoring of 100% of critical data for all patients included in the analysis was achieved, and despite of the pandemic context, a conform consent was recovered for more than 99% of patients. Results of the study were published in May and September 2021. Discussion/conclusion: The main monitoring objective was met thanks to the mobilization of considerable personnel resources, within a very tight time frame and external hurdles. There is a need for further reflection to adapt the lessons learned from this experience to the context of routine practice and to improve the response of French academic research during a future epidemic.
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- 2023
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