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1. Innate immune response in acute critical illness: a narrative review

Author

Laure Stiel, Alexandre Gaudet, Sara Thietart, Hélène Vallet, Paul Bastard, Guillaume Voiriot, Mehdi Oualha, Benjamine Sarton, Hatem Kallel, Nicolas Brechot, Louis Kreitmann, Sarah Benghanem, Jérémie Joffre, Youenn Jouan, and la Commission de Recherche Translationnelle de la Société de Réanimation en Langue Française

Subjects
Innate immunity, Immunothrombosis, Immunosenescence, Trained immunity, Acute critical illness, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies. Main text Understanding the underlying biological concepts supporting therapeutic strategies modulating immune response is essential in decision-making. We will develop the multiple facets of innate immune response, especially its cellular aspects, and its interaction with other defense mechanisms. We will first describe the pathophysiological mechanisms of initiation of innate immune response and its implication during ACI. We will then develop the amplification of innate immunity mediated by multiple effectors. Our review will mainly focus on myeloid and lymphoid cellular effectors, the major actors involved in innate immune-mediated organ failure. We will third discuss the interaction and integration of innate immune response in a global view of host defense, thus considering interaction with non-immune cells through immunothrombosis, immunometabolism and long-term reprogramming via trained immunity. The last part of this review will focus on the specificities of the immune response in children and the older population. Conclusions Recent understanding of the innate immune response integrates immunity in a highly dynamic global vision of host response. A better knowledge of the implicated mechanisms and their tissue-compartmentalization allows to characterize the individual immune profile, and one day eventually, to develop individualized bench-to-bedside immunomodulation approaches as an adjuvant resuscitation strategy.

Published
2024
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4. Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life

Author

Sitbon, Alexandre, Hauw-Berlemont, Caroline, Mebarki, Miryam, Heming, Nicholas, Mayaux, Julien, Diehl, Jean-Luc, Demoule, Alexandre, Annane, Djillali, Marois, Clémence, Demeret, Sophie, Weiss, Emmanuel, Voiriot, Guillaume, Fartoukh, Muriel, Constantin, Jean‐Michel, Mégarbane, Bruno, Plantefève, Gaëtan, Boucher-Pillet, Hélène, Churlaud, Guillaume, Cras, Audrey, Maheux, Camille, Pezzana, Chloé, Diallo, Mamadou Hassimiou, Lebbah, Said, Ropers, Jacques, Salem, Joe-Elie, Straus, Christian, Menasché, Philippe, Larghero, Jérôme, and Monsel, Antoine

Published
2024
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7. Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life

Author

Alexandre Sitbon, Caroline Hauw-Berlemont, Miryam Mebarki, Nicholas Heming, Julien Mayaux, Jean-Luc Diehl, Alexandre Demoule, Djillali Annane, Clémence Marois, Sophie Demeret, Emmanuel Weiss, Guillaume Voiriot, Muriel Fartoukh, Jean‐Michel Constantin, Bruno Mégarbane, Gaëtan Plantefève, Hélène Boucher-Pillet, Guillaume Churlaud, Audrey Cras, Camille Maheux, Chloé Pezzana, Mamadou Hassimiou Diallo, Said Lebbah, Jacques Ropers, Joe-Elie Salem, Christian Straus, Philippe Menasché, Jérôme Larghero, Antoine Monsel, and APHP STROMA–CoV‐2 Collaborative Research Group

Subjects
Severe acute respiratory syndrome coronavirus‐2, Acute respiratory distress syndrome, Umbilical cord‐ derived mesenchymal stromal cells, Long-term outcomes, Follow-up Studies, Quality of Life at six and twelve months after hospital discharge, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract

Abstract Background The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort. Methods A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS–CoV-2-related early (

Published
2024
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8. Routes of SARS-Cov2 transmission in the intensive care unit: A multicentric prospective study

Author

Yacine Tandjaoui-Lambiotte, Alexandre Elabbadi, Boubaya Marouane, Sebastien Besset, Damien Roux, Nathan Ebstein, Pascal Pineau, Agnes Marchio, Coralie Bloch-Queyrat, Alexandra Lomont, Chakib-Ahmed Alloui, Athenaïs Gerber, Heloise Delagrèverie, Yves Cohen, Jean Ralph Zahar, and Guillaume Voiriot

Subjects
SARS-CoV-2, Viral shedding, Airborne, Viral contamination, Intensive care unit, Infectious and parasitic diseases, RC109-216, Public aspects of medicine, RA1-1270
Abstract

Background: The risk of SARS-CoV-2 transmission to health care workers in intensive care units (ICU) and the contribution of airborne and fomites to SARS-CoV-2 transmission remain unclear. To assess the rate of air and surface contamination and identify risk factors associated with this contamination in patients admitted to the ICU for acute respiratory failure due to SARS-CoV-2 pneumonia. Methods: Prospective multicentric non-interventional study conducted from June 2020 to November 2020 in 3 French ICUs. For each enrolled patient, 3 predefined surfaces were swabbed, 2 air samples at 1 m and 3 m from the patient’s mouth and face masks of 3 health care workers (HCW) were collected within the first 48 h of SARS-CoV-2 positive PCR in a respiratory sample. Droplet digital PCR and quantitative PCR were performed on different samples, respectively. Results: Among 150 included patients, 5 (3.6%, 95%CI: 1.2% to 8.2%) had positive ddPCR on air samples at 1 m or 3 m. Seventy-one patients (53.3%, CI95%: 44.5% to 62.0%) had at least one surface positive. Face masks worn by HCW were positive in 6 patients (4.4%, CI: 1.6% to 9.4%). The threshold of RT-qPCR of the respiratory sample performed at inclusion (odds ratio, OR= 0.88, 95%CI: 0.83 to 0.93, p

Published
2024
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9. Human metapneumovirus infection is associated with a substantial morbidity and mortality burden in adult inpatients

Author

Quentin Philippot, Blandine Rammaert, Gaëlle Dauriat, Cédric Daubin, Frédéric Schlemmer, Adrien Costantini, Yacine Tandjaoui-Lambiotte, Mathilde Neuville, Emmanuelle Desrochettes, Alexis Ferré, Laetitia Bodet Contentin, François-Xavier Lescure, Bruno Megarbane, Antoine Belle, Jean Dellamonica, Sylvain Jaffuel, Jean-Luc Meynard, Jonathan Messika, Nicolas Lau, Nicolas Terzi, Isabelle Runge, Olivier Sanchez, Benjamin Zuber, Emmanuel Guerot, Anahita Rouze, Patricia Pavese, François Bénézit, Jean-Pierre Quenot, Xavier Souloy, Anne Lyse Fanton, David Boutoille, Vincent Bunel, Astrid Vabret, Jacques Gaillat, Anne Bergeron, Nathanaël Lapidus, Muriel Fartoukh, and Guillaume Voiriot

Subjects
Human metapneumovirus, Pneumonia, Viral pneumonia, Respiratory viruses, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients. Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used. Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62–84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2–7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course. Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients.

Published
2024
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10. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author

Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, 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 Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia

Subjects
HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Published
2024
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11. Diagnostic yield of viral multiplex PCR during acute exacerbation of COPD admitted to the intensive care unit: a pilot study

Author

Costa Salachas, Cherifa Gounane, Gaëtan Beduneau, Julien Lopinto, Matthieu Turpin, Corinne Amiel, Antoine Cuvelier, Marie Gueudin, Guillaume Voiriot, and Muriel Fartoukh

Subjects
Medicine, Science
Abstract

Abstract Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of admission to the intensive care unit, often triggered by a respiratory tract infection of bacterial or viral aetiology. Managing antibiotic therapy in this context remains a challenge. Respiratory panel molecular tests allow identifying viral aetiologies of AECOPD. We hypothesized that the systematic use of a respiratory multiplex PCR (mPCR) would help antibiotics saving in severe AECOPD. Our objectives were to describe the spectrum of infectious aetiologies of severe AECOPD, using a diagnostic approach combining conventional diagnostic tests and mPCR, and to measure antibiotics exposure. The study was bicentric, prospective, observational, and included 105 critically ill patients with a severe AECOPD of presumed infectious aetiology, in whom a respiratory mPCR with a viral panel was performed in addition to conventional microbiological tests. Altogether, the microbiological documentation rate was 50%, including bacteria alone (19%), respiratory viruses alone (16%), and mixed viruses and bacterial species (16%). The duration of antibiotic therapy was shorter in patients without documented bacterial infection (5.6 vs. 9 days; P = 0.0006). This pilot study suggests that molecular tests may help for the proper use of anti-infective treatments in critically ill patients with severe AECOPD.

Published
2024
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12. Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Author

Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Póvoa, Pedro, Coelho, Luis, Metaxa, Victoria, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Andreasen, Jo Bønding, Péju, Edwige, Nielsen, Lene Bjerregaard, Hvas, Christine Lodberg, Dufranc, Etienne, Canet, Emmanuel, Lundqvist, Linda, Wright, Christopher John, Schmidt, Julien, Uhel, Fabrice, Ait-Oufella, Hafid, Krag, Mette, Cos Badia, Elisabet, Díaz-Lagares, Cándido, Menat, Sophie, Voiriot, Guillaume, Clausen, Niels Erikstrup, Lorentzen, Kristian, Kvåle, Reidar, Hildebrandt, Thomas, Holten, Aleksander Rygh, Strand, Kristian, Tzalavras, Asterios, Bestle, Morten Heiberg, Klepstad, Pål, Fernandez, Sara, Vimpere, Damien, Paulino, Carolina, Graça, Carina, Lueck, Catherina, Juhl, Christian Svendsen, Costa, Carolina, Bådstøløkken, Per Martin, Miranda, Teresa, Lêdo, Lia Susana Aires, Sousa Torres, Joao Carlos, Granholm, Anders, Møller, Morten Hylander, and Russell, Lene

Published
2023
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13. Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study

Author

de Prost, Nicolas, Audureau, Etienne, Préau, Sébastien, Favory, Raphaël, Guigon, Aurélie, Bay, Pierre, Heming, Nicholas, Gault, Elyanne, Pham, Tài, Chaghouri, Amal, Voiriot, Guillaume, Morand-Joubert, Laurence, Jochmans, Sébastien, Pitsch, Aurélia, Meireles, Sylvie, Contou, Damien, Henry, Amandine, Joseph, Adrien, Chaix, Marie-Laure, Uhel, Fabrice, Descamps, Diane, Emery, Malo, Garcia-Sanchez, Claudio, Luyt, Charles-Edouard, Marot, Stéphane, Pène, Frédéric, Lhonneur, Anne-Sophie, Gaudry, Stéphane, Brichler, Ségolène, Picard, Lucile, Mekontso Dessap, Armand, Rodriguez, Christophe, Pawlotsky, Jean-Michel, and Fourati, Slim

Published
2023
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14. SARS-CoV-2 variants and mutational patterns: relationship with risk of ventilator-associated pneumonia in critically ill COVID-19 patients in the era of dexamethasone

Author

Razazi, Keyvan, Martins Bexiga, Anissa, Arrestier, Romain, Peiffer, Bastien, Voiriot, Guillaume, Luyt, Charles-Edouard, Urbina, Tomas, Mayaux, Julien, Pham, Tài, Roux, Damien, Bellaiche, Raphael, AIt Hamou, Zakaria, Gaudry, Stéphane, Azoulay, Elie, Mekontso Dessap, Armand, Rodriguez, Christophe, Pawlotsky, Jean-Michel, Fourati, Slim, and de Prost, Nicolas

Published
2023
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15. Restrictive use of Restraints and Delirium Duration in the Intensive Care Unit (R2D2-ICU): protocol for a French multicentre parallel-group open-label randomised controlled trial

Author

Jean-François Timsit, Damien Contou, Julien Schmidt, Carine Roy, Romain Sonneville, Lila Bouadma, Armand Mekontso Dessap, Michel Djibré, Camille Couffignal, Juliette Audibert, Pierre Jaquet, Virginie Godard, Romane Bellot, Fariza Lamara, Tchoubou Tona, Florian Sigaud, Adam Celier, Claire Bourel, Fatiha Essardy, Renaud Cornic, ABGRALL Gwenole, ARRESTIER Romain, AUDIBERT Juliette, AUGY Jean loup, BAGATE François, BAY Pierre, BEGOT Erwan, BEN SALAH Adel, BENELLI Brice, BERTI Enora, BERTIER Astrid, BEURTON Alexandra, BILLIET Pierre-Antoine, BOUADMA Lila, BOUGNAUD Joanna, BOUILLAND Anne Laure, BOUJELBEN Mohamed, BUREAU Côme, CANDILLE Clara, CARIOU Erwann, CARTEAUX Guillaume, CATANO Jenifer, CAVALEIRO Pedro, CELIER Adam, CHAFIOTTE Pierre, CIRILLO Giulia, CLERC Sébastien, CONIA Alexandre, CORDIER Charlotte, COUPRY Louis-Marie, DA SILVA Daniel, DARTEVEL Anais, DE MONTMOLLIN Etienne, DE MONTMOLLIN Nina, DE PROST Nicolas, DECAVELE Maxens, DELERIS Robin, DEMOULE Alexandre, DESNOS Cyrielle, DESSAJAN Julien, DIEMOZ Marie-Claire, DO REGO Hermann, DO VALE Julien, DRES Martin, DUFRANC Etienne, EJZENBERG Michael, ELABBADI Alexandre, FLOCH Pierre Edouard, FOSSE Quentin, FRAPARD Thomas, GAILLET Antoine, GALERNEAU Louis-Marie, GENDREAU Ségolène, GONCALVES CAVALEIRO Pedro, GONTIER Olivier, HAMROUNI Mouldi, HAUDEBOURG Anne-Fleur, HAUDEBOURG Luc, JOLLY Florian, LA MAREC Julien, LABEDADE Pascale, LAVILLEGRAND Jean-Rémi, LECRONIER Marie, LOPINTO Julien, MASI Paul, MAYAUX Julien, MENAT Sophie, MONCOMBLE Elsa, MORAWIEC Elise, NAGLE Sophie, NEMLAGHI Safaa, PICARD Benjamin, PICHON Jeremie, PLAIS Henri, RAZAZI Keyvan, RIGAULT Guillaume, SIGAUD Florian, SONNEVILLE Romain, THY Michael, TIMSIT Jean-François, TUFFET Samuel, TURPIN Matthieu, VINCENT Xavier, VOIRIOT Guillaume, WICKY Paul-Henri, and WINDSOR Camille

Subjects
Medicine
Abstract

Introduction Physical restraint (PR) is prescribed in patients receiving invasive mechanical ventilation in the intensive care unit (ICU) to avoid unplanned removal of medical devices. However, it is associated with an increased risk of delirium. We hypothesise that a restrictive use of PR, as compared with a systematic use, could reduce the duration of delirium in ICU patients receiving invasive mechanical ventilation.Methods and analysis The Restrictive use of Restraints and Delirium Duration in ICU (R2D2-ICU) study is a national multicentric, parallel-group, randomised (1:1) open-label, controlled, superiority trial, which will be conducted in 10 ICUs. A total of 422 adult patients requiring invasive mechanical ventilation for an expected duration of at least 48 hours and eligible for prescription of PR will be randomly allocated within 6 hours from intubation to either the restrictive PR use group or the systematic PR use group, until day 14, ICU discharge or death, whichever comes first. In both groups, PR will consist of the use of wrist straps. The primary endpoint will be delirium or coma-free days, defined as the number of days spent alive in the ICU without coma or delirium within the first 14 days after randomisation. Delirium will be assessed using the Confusion Assessment Method-ICU twice daily. Key secondary endpoints will encompass agitation episodes, opioid, propofol, benzodiazepine and antipsychotic drug exposure during the 14-day intervention period, along with a core outcome set of measures evaluated 90 days postrandomisation.Ethics and dissemination The R2D2-ICU study has been approved by the Comité de Protection des Personnes (CPP) ILE DE FRANCE III—PARIS (CPP19.09.06.37521) on June 10th, 2019). Participant recruitment started on 25 January 2021. Results will be published in international peer-reviewed medical journals and presented at conferences.Trial registration number NCT04273360.

Published
2024
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16. Correction: Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Author

Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Póvoa, Pedro, Coelho, Luis, Metaxa, Victoria, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Andreasen, Jo Bønding, Péju, Edwige, Nielsen, Lene Bjerregaard, Hvas, Christine Lodberg, Dufranc, Etienne, Canet, Emmanuel, Lundqvist, Linda, Wright, Christopher John, Schmidt, Julien, Uhel, Fabrice, Ait-Oufella, Hafid, Krag, Mette, Cos Badia, Elisabet, Díaz-Lagares, Cándido, Menat, Sophie, Voiriot, Guillaume, Clausen, Niels Erikstrup, Lorentzen, Kristian, Kvåle, Reidar, Hildebrandt, Thomas, Holten, Aleksander Rygh, Strand, Kristian, Tzalavras, Asterios, Bestle, Morten Heiberg, Klepstad, Pål, Fernandez, Sara, Vimpere, Damien, Paulino, Carolina, Graça, Carina, Lueck, Catherina, Juhl, Christian Svendsen, Costa, Carolina, Bådstøløkken, Per Martin, Miranda, Teresa, Lêdo, Lia Susana Aires, Sousa Torres, Joao Carlos, Granholm, Anders, Møller, Morten Hylander, and Russell, Lene

Published
2023
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18. Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study

Author

Nicolas de Prost, Etienne Audureau, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Pierre Bay, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Guillaume Voiriot, Laurence Morand-Joubert, Sébastien Jochmans, Aurélia Pitsch, Sylvie Meireles, Damien Contou, Amandine Henry, Adrien Joseph, Marie-Laure Chaix, Fabrice Uhel, Diane Descamps, Malo Emery, Claudio Garcia-Sanchez, Charles-Edouard Luyt, Stéphane Marot, Frédéric Pène, Anne-Sophie Lhonneur, Stéphane Gaudry, Ségolène Brichler, Lucile Picard, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, Slim Fourati, and the SEVARVIR investigators

Subjects
SARS-CoV-2, Omicron, Sublineage, COVID-19, Acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. Results The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as “BA.2” (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as “BA.4/BA.5”, and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as “BQ.1.1”. The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. Conclusions Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.

Published
2023
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19. SARS-CoV-2 variants and mutational patterns: relationship with risk of ventilator-associated pneumonia in critically ill COVID-19 patients in the era of dexamethasone

Author

Keyvan Razazi, Anissa Martins Bexiga, Romain Arrestier, Bastien Peiffer, Guillaume Voiriot, Charles-Edouard Luyt, Tomas Urbina, Julien Mayaux, Tài Pham, Damien Roux, Raphael Bellaiche, Zakaria AIt Hamou, Stéphane Gaudry, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, Slim Fourati, and Nicolas de Prost

Subjects
Medicine, Science
Abstract

Abstract We aimed to explore the relationships between specific viral mutations/mutational patterns and ventilator-associated pneumonia (VAP) occurrence in COVID-19 patients admitted in intensive care units between October 1, 2020, and May 30, 2021. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing. In this prospective multicentre cohort study, 259 patients were included. 222 patients (47%) had been infected with pre-existing ancestral variants, 116 (45%) with variant α, and 21 (8%) with other variants. 153 patients (59%) developed at least one VAP. There was no significant relationship between VAP occurrence and a specific SARS CoV-2 lineage/sublineage or mutational pattern.

Published
2023
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20. Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study

Author

Romain Arrestier, Paul Bastard, Thibaut Belmondo, Guillaume Voiriot, Tomas Urbina, Charles-Edouard Luyt, Adrian Gervais, Lucy Bizien, Lauriane Segaux, Mariem Ben Ahmed, Raphaël Bellaïche, Taï Pham, Zakaria Ait-Hamou, Damien Roux, Raphael Clere-Jehl, Elie Azoulay, Stéphane Gaudry, Julien Mayaux, Nicolas Fage, Hafid Ait-Oufella, Elsa Moncomble, Mélodie Parfait, Karim Dorgham, Guy Gorochov, Armand Mekontso-Dessap, Florence Canoui-Poitrine, Jean-Laurent Casanova, Sophie Hue, and Nicolas de Prost

Subjects
COVID-19, Interferon, Auto-antibodies, Acute respiratory distress syndrome, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs. Results We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70–100) vs. 90% (60–100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04–1.08], p

Published
2022
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21. Spontaneous pneumomediastinum: a surrogate of P-SILI in critically ill COVID-19 patients

Author

Alexandre Elabbadi, Tomas Urbina, Enora Berti, Damien Contou, Gaëtan Plantefève, Quintana Soulier, Audrey Milon, Guillaume Carteaux, Guillaume Voiriot, Muriel Fartoukh, and Aude Gibelin

Subjects
Pneumomediastinum, Coronavirus disease 2019, Pneumonia, Intensive care unit, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Spontaneous pneumomediastinum (SP) has been described early during the COVID-19 pandemic in large series of patients with severe pneumonia, but most patients were receiving invasive mechanical ventilation (IMV) at the time of SP diagnosis. In this retrospective multicenter observational study, we aimed at describing the prevalence and outcomes of SP during severe COVID-19 with pneumonia before any IMV, to rule out mechanisms induced by IMV in the development of pneumomediastinum. Among 549 patients, 21 patients (4%) developed a SP while receiving non-invasive respiratory support, after a median of 6 days [4–12] from ICU admission. The proportion of patients requiring IMV was similar. However, the time to tracheal intubation was longer in patients with SP (6 days [5–13] vs. 2 days [1–4]; P = 0.00002), with a higher first-line use of non-invasive ventilation (n = 11; 52% vs. n = 150; 28%; P = 0.02). The 21 patients who developed a SP had persisting signs of severe lung disease and respiratory failure with lower ROX index between ICU admission and occurrence of SP (3.94 [3.15–5.55] at admission vs. 3.25 [2.73–4.02] the day preceding SP; P = 0.1), which may underline potential indirect signals of Patient-self inflicted lung injury (P-SILI). In this series of critically ill COVID-19 patients, the prevalence of SP without IMV was not uncommon, affecting 4% of patients. They received more often vasopressors and had a longer ICU length of stay, as compared with their counterparts. One pathophysiological mechanism may potentially be carried out by P-SILI related to a prolonged respiratory failure, as underlined by a delayed use of IMV and the evolution of the ROX index between ICU admission and the day preceding SP.

Published
2022
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22. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Author

Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stéphane Gaudry, Ségolène Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Louise-Marie Jandeaux, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Djillali Annane, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, and Slim Fourati

Subjects
Science
Abstract

SARS-CoV-2 variant Omicron has been suggested to cause less severe disease. This prospective study shows that the clinical phenotype in patients infected with Omicron differs from patients infected with Delta but no association between Delta and Omicron including sublineages and mortality was observed.

Published
2022
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23. Relationship between corticosteroid use and incidence of ventilator-associated pneumonia in COVID-19 patients: a retrospective multicenter study

Author

Ouriel Saura, Anahita Rouzé, Ignacio Martin-Loeches, Pedro Povoa, Louis Kreitmann, Antoni Torres, Matthieu Metzelard, Damien Du Cheyron, Fabien Lambiotte, Fabienne Tamion, Marie Labruyere, Claire Boulle Geronimi, Charles-Edouard Luyt, Martine Nyunga, Olivier Pouly, Arnaud W. Thille, Bruno Megarbane, Anastasia Saade, Eleni Magira, Jean-François Llitjos, Iliana Ioannidou, Alexandre Pierre, Jean Reignier, Denis Garot, Jean-Luc Baudel, Guillaume Voiriot, Gaëtan Plantefeve, Elise Morawiec, Pierre Asfar, Alexandre Boyer, Armand Mekontso-Dessap, Fotini Bardaka, Emili Diaz, Christophe Vinsonneau, Pierre-Edouard Floch, Nicolas Weiss, Adrian Ceccato, Antonio Artigas, David Nora, Alain Duhamel, Julien Labreuche, Saad Nseir, and coVAPid Study Group

Subjects
SARS-CoV-2, COVID-19, Ventilator-associated lower respiratory tract infections, Corticosteroids, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. Methods Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox’s proportional hazard models with adjustment on pre-specified confounders. Results Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17–1.31) at day 2, 0.95 (0.63–1.42) at day 7, 1.48 (1.01–2.16) at day 14 and 1.94 (1.09–3.46) at day 21. Conclusions No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.

Published
2022
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24. PupillOmetry for preDIction of DeliriUM in ICU (PODIUM): protocol for a prospective multicentre cohort study

Author

Emmanuel Guerot, Bertrand Hermann, Stéphane Gaudry, Jean-François Timsit, Maxens Decavèle, Alain Combes, Jean-Paul Mira, Benjamin Assouline, Alexandre Demoule, Muriel Fartoukh, Romain Sonneville, Lila Bouadma, Yves Cohen, Guillaume Voiriot, Camille Couffignal, Etienne De Montmollin, Jean-Luc Diehl, Pierre Jaquet, Coralie Tardivon, Sarah Benghanem, Thomas Rambaud, Virginie Godard, Romane Bellot, Daniel Da Silva, Julien Dessajan, Michael Thy, Marc Doman, Hermann Do Rego, Michael Ejzenberg, Erwann Cariou, Simona Presente, Paul-Henri Wicky, Mario Rienzo, Mariem Dlela, Fariza Lamara, Nathalie Marin, Juliette Pelle, Stephanie Cossec, Smina Hadj Mahfoud, Tchoubou Tona, Khalil Chaibi, Eleonore Bouchereau, Antoine Troger, Julie Langlais, Nicolas Peron, Caroline Hauw-Berlemont, and Nicolas Brechot

Subjects
Medicine
Abstract

Introduction Delirium is a severe complication that is associated with short-term adverse events, prolonged hospital stay and neurological sequelae in survivors. Automated pupillometry is an easy-to-use device that allows for accurate objective assessment of the pupillary light responses in comatose patients in the intensive care unit (ICU). Whether automated pupillometry might predict delirium in critically ill patients is not known. We hypothesise that automated pupillometry could predict the occurrence of delirium in critically ill patients without primary brain injury, requiring more than 48 hours of invasive mechanical ventilation in the ICU.Methods and analysis The PupillOmetry for preDIction of DeliriUM in ICU (PODIUM) study is a prospective cohort study, which will be conducted in eight French ICUs in the Paris area. We aim to recruit 213 adult patients requiring invasive mechanical ventilation for more than 48 hours. Automated pupillometry (Neurological Pupil Index; NPi-200, Neuroptics) will be assessed two times per day for 7 days. Delirium will be assessed using the Confusion Assessment Method in ICU two times per day over 14 days in non-comatose patients (Richmond Agitation and Sedation Scale ≥−3).The predictive performances of the seven automated pupillometry parameters (ie, pupillary diameter, variation of the pupillary diameter, pupillary constriction speed, pupillary dilatation speed, photomotor reflex latency, NPi and symmetry of pupillary responses) measured to detect the delirium occurrence within 14 days will be the main outcomes. Secondary outcomes will be the predictive performances of the seven automated pupillometry parameters to detect complications related to delirium, ICU length of stay, mortality, functional and cognitive outcomes at 90 days.Ethics and dissemination The PODIUM study has been approved by an independent ethics committee, the Comité de Protection des Personnes (CPP) OUEST IV—NANTES (CPP21.02.15.45239 32/21_3) on 06 April 2021). Participant recruitment started on 15 April 2022. Results will be published in international peer-reviewed medical journals and presented at conferences.Trial registration number NCT05248035; clinicaltrials.gov.

Published
2023
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25. Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Author

Guillaume Voiriot, Mehdi Oualha, Alexandre Pierre, Charlotte Salmon-Gandonnière, Alexandre Gaudet, Youenn Jouan, Hatem Kallel, Peter Radermacher, Dominique Vodovar, Benjamine Sarton, Laure Stiel, Nicolas Bréchot, Sébastien Préau, Jérémie Joffre, and la CRT de la SRLF

Subjects
Post-ICU syndrome, Chronic critical illness, Long-term outcome, ICU sequelae, Neuromuscular disorders, Cognitive impairment, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Post‐intensive care syndrome (PICS) encompasses physical, cognition, and mental impairments persisting after intensive care unit (ICU) discharge. Ultimately it significantly impacts the long‐term prognosis, both in functional outcomes and survival. Thus, survivors often develop permanent disabilities, consume a lot of healthcare resources, and may experience prolonged suffering. This review aims to present the multiple facets of the PICS, decipher its underlying mechanisms, and highlight future research directions. Main text This review abridges the translational data underlying the multiple facets of chronic critical illness (CCI) and PICS. We focus first on ICU-acquired weakness, a syndrome characterized by impaired contractility, muscle wasting, and persisting muscle atrophy during the recovery phase, which involves anabolic resistance, impaired capacity of regeneration, mitochondrial dysfunction, and abnormalities in calcium homeostasis. Second, we discuss the clinical relevance of post-ICU cognitive impairment and neuropsychological disability, its association with delirium during the ICU stay, and the putative role of low-grade long-lasting inflammation. Third, we describe the profound and persistent qualitative and quantitative alteration of the innate and adaptive response. Fourth, we discuss the biological mechanisms of the progression from acute to chronic kidney injury, opening the field for renoprotective strategies. Fifth, we report long-lasting pulmonary consequences of ARDS and prolonged mechanical ventilation. Finally, we discuss several specificities in children, including the influence of the child’s pre-ICU condition, development, and maturation. Conclusions Recent understandings of the biological substratum of the PICS’ distinct features highlight the need to rethink our patient trajectories in the long term. A better knowledge of this syndrome and precipitating factors is necessary to develop protocols and strategies to alleviate the CCI and PICS and ultimately improve patient recovery.

Published
2022
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26. Identification of bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome in critically ill COVID-19 patients

Author

Guillaume Voiriot, Karim Dorgham, Guillaume Bachelot, Anne Fajac, Laurence Morand-Joubert, Christophe Parizot, Grigorios Gerotziafas, Dominique Farabos, Germain Trugnan, Thibaut Eguether, Clarisse Blayau, Michel Djibré, Alexandre Elabbadi, Aude Gibelin, Vincent Labbé, Antoine Parrot, Matthieu Turpin, Jacques Cadranel, Guy Gorochov, Muriel Fartoukh, and Antonin Lamazière

Subjects
Medicine, Science
Abstract

Abstract The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30–4.41] vs. 9.53 [2.56–19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.

Published
2022
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27. Risk Factors for Intra-Abdominal Candidiasis in Intensive Care Units: Results from EUCANDICU Study

Author

Bassetti, Matteo, Vena, Antonio, Giacobbe, Daniele R., Trucchi, Cecilia, Ansaldi, Filippo, Antonelli, Massimo, Adamkova, Vaclava, Alicino, Cristiano, Almyroudi, Maria-Panagiota, Atchade, Enora, Azzini, Anna M., Brugnaro, Pierluigi, Carannante, Novella, Peghin, Maddalena, Berruti, Marco, Carnelutti, Alessia, Castaldo, Nadia, Corcione, Silvia, Cortegiani, Andrea, Dimopoulos, George, Dubler, Simon, García-Garmendia, José L., Girardis, Massimo, Cornely, Oliver A., Ianniruberto, Stefano, Kullberg, Bart Jan, Lagrou, Katrien, Lebihan, Clement, Luzzati, Roberto, Malbrain, Manu, Merelli, Maria, Marques, Ana J., Martin-Loeches, Ignacio, Mesini, Alessio, Paiva, José-Artur, Raineri, Santi Maurizio, Rautemaa-Richardson, Riina, Schouten, Jeroen, Spapen, Herbert, Tasioudis, Polychronis, Timsit, Jean-François, Tisa, Valentino, Tumbarello, Mario, Van den Berg, Charlotte H. S. B., Veber, Benoit, Venditti, Mario, Voiriot, Guillaume, Wauters, Joost, Zappella, Nathalie, and Montravers, Philippe

Published
2022
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28. Identification of bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome in critically ill COVID-19 patients

Author

Voiriot, Guillaume, Dorgham, Karim, Bachelot, Guillaume, Fajac, Anne, Morand-Joubert, Laurence, Parizot, Christophe, Gerotziafas, Grigorios, Farabos, Dominique, Trugnan, Germain, Eguether, Thibaut, Blayau, Clarisse, Djibré, Michel, Elabbadi, Alexandre, Gibelin, Aude, Labbé, Vincent, Parrot, Antoine, Turpin, Matthieu, Cadranel, Jacques, Gorochov, Guy, Fartoukh, Muriel, and Lamazière, Antonin

Published
2022
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29. Relationship between corticosteroid use and incidence of ventilator-associated pneumonia in COVID-19 patients: a retrospective multicenter study

Author

Saura, Ouriel, Rouzé, Anahita, Martin-Loeches, Ignacio, Povoa, Pedro, Kreitmann, Louis, Torres, Antoni, Metzelard, Matthieu, Du Cheyron, Damien, Lambiotte, Fabien, Tamion, Fabienne, Labruyere, Marie, Boulle Geronimi, Claire, Luyt, Charles-Edouard, Nyunga, Martine, Pouly, Olivier, Thille, Arnaud W., Megarbane, Bruno, Saade, Anastasia, Magira, Eleni, Llitjos, Jean-François, Ioannidou, Iliana, Pierre, Alexandre, Reignier, Jean, Garot, Denis, Baudel, Jean-Luc, Voiriot, Guillaume, Plantefeve, Gaëtan, Morawiec, Elise, Asfar, Pierre, Boyer, Alexandre, Mekontso-Dessap, Armand, Bardaka, Fotini, Diaz, Emili, Vinsonneau, Christophe, Floch, Pierre-Edouard, Weiss, Nicolas, Ceccato, Adrian, Artigas, Antonio, Nora, David, Duhamel, Alain, Labreuche, Julien, and Nseir, Saad

Published
2022
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32. Correction to: Characteristics and prognosis of bloodstream infection in patients with COVID‑19 admitted in the ICU: an ancillary study of the COVID‑ICU study

Author

Massart, Nicolas, Maxime, Virginie, Fillatre, Pierre, Razazi, Keyvan, Ferré, Alexis, Moine, Pierre, Legay, Francois, Voiriot, Guillaume, Amara, Marlene, Santi, Francesca, Nseir, Saad, Marque-Juillet, Stephanie, Bounab, Rania, Barbarot, Nicolas, Bruneel, Fabrice, and Luyt, Charles-Edouard

Published
2022
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33. Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial

Author

Monsel, Antoine, Hauw-Berlemont, Caroline, Mebarki, Miryam, Heming, Nicholas, Mayaux, Julien, Nguekap Tchoumba, Otriv, Diehl, Jean-Luc, Demoule, Alexandre, Annane, Djillali, Marois, Clémence, Demeret, Sophie, Weiss, Emmanuel, Voiriot, Guillaume, Fartoukh, Muriel, Constantin, Jean-Michel, Mégarbane, Bruno, Plantefève, Gaëtan, Malard-Castagnet, Stéphanie, Burrel, Sonia, Rosenzwajg, Michelle, Tchitchek, Nicolas, Boucher-Pillet, Hélène, Churlaud, Guillaume, Cras, Audrey, Maheux, Camille, Pezzana, Chloé, Diallo, Mamadou Hassimiou, Ropers, Jacques, Menasché, Philippe, and Larghero, Jérôme

Published
2022
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34. Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study

Author

Rouzé, Anahita, Lemaitre, Elise, Martin-Loeches, Ignacio, Povoa, Pedro, Diaz, Emili, Nyga, Rémy, Torres, Antoni, Metzelard, Matthieu, Du Cheyron, Damien, Lambiotte, Fabien, Tamion, Fabienne, Labruyere, Marie, Boulle Geronimi, Claire, Luyt, Charles-Edouard, Nyunga, Martine, Pouly, Olivier, Thille, Arnaud W., Megarbane, Bruno, Saade, Anastasia, Magira, Eleni, Llitjos, Jean-François, Ioannidou, Iliana, Pierre, Alexandre, Reignier, Jean, Garot, Denis, Kreitmann, Louis, Baudel, Jean-Luc, Voiriot, Guillaume, Plantefeve, Gaëtan, Morawiec, Elise, Asfar, Pierre, Boyer, Alexandre, Mekontso-Dessap, Armand, Makris, Demosthenes, Vinsonneau, Christophe, Floch, Pierre-Edouard, Marois, Clémence, Ceccato, Adrian, Artigas, Antonio, Gaudet, Alexandre, Nora, David, Cornu, Marjorie, Duhamel, Alain, Labreuche, Julien, and Nseir, Saad

Published
2022
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36. Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study

Author

Arrestier, Romain, Bastard, Paul, Belmondo, Thibaut, Voiriot, Guillaume, Urbina, Tomas, Luyt, Charles-Edouard, Gervais, Adrian, Bizien, Lucy, Segaux, Lauriane, Ben Ahmed, Mariem, Bellaïche, Raphaël, Pham, Taï, Ait-Hamou, Zakaria, Roux, Damien, Clere-Jehl, Raphael, Azoulay, Elie, Gaudry, Stéphane, Mayaux, Julien, Fage, Nicolas, Ait-Oufella, Hafid, Moncomble, Elsa, Parfait, Mélodie, Dorgham, Karim, Gorochov, Guy, Mekontso-Dessap, Armand, Canoui-Poitrine, Florence, Casanova, Jean-Laurent, Hue, Sophie, and de Prost, Nicolas

Published
2022
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37. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Author

de Prost, Nicolas, Audureau, Etienne, Heming, Nicholas, Gault, Elyanne, Pham, Tài, Chaghouri, Amal, de Montmollin, Nina, Voiriot, Guillaume, Morand-Joubert, Laurence, Joseph, Adrien, Chaix, Marie-Laure, Préau, Sébastien, Favory, Raphaël, Guigon, Aurélie, Luyt, Charles-Edouard, Burrel, Sonia, Mayaux, Julien, Marot, Stéphane, Roux, Damien, Descamps, Diane, Meireles, Sylvie, Pène, Frédéric, Rozenberg, Flore, Contou, Damien, Henry, Amandine, Gaudry, Stéphane, Brichler, Ségolène, Timsit, Jean-François, Kimmoun, Antoine, Hartard, Cédric, Jandeaux, Louise-Marie, Fafi-Kremer, Samira, Gabarre, Paul, Emery, Malo, Garcia-Sanchez, Claudio, Jochmans, Sébastien, Pitsch, Aurélia, Annane, Djillali, Azoulay, Elie, Mekontso Dessap, Armand, Rodriguez, Christophe, Pawlotsky, Jean-Michel, and Fourati, Slim

Published
2022
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38. Author Correction: Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Author

de Prost, Nicolas, Audureau, Etienne, Heming, Nicholas, Gault, Elyanne, Pham, Tài, Chaghouri, Amal, de Montmollin, Nina, Voiriot, Guillaume, Morand-Joubert, Laurence, Joseph, Adrien, Chaix, Marie-Laure, Préau, Sébastien, Favory, Raphaël, Guigon, Aurélie, Luyt, Charles-Edouard, Burrel, Sonia, Mayaux, Julien, Marot, Stéphane, Roux, Damien, Descamps, Diane, Meireles, Sylvie, Pène, Frédéric, Rozenberg, Flore, Contou, Damien, Henry, Amandine, Gaudry, Stéphane, Brichler, Ségolène, Timsit, Jean-François, Kimmoun, Antoine, Hartard, Cédric, Jandeaux, Louise-Marie, Fafi-Kremer, Samira, Gabarre, Paul, Emery, Malo, Garcia-Sanchez, Claudio, Jochmans, Sébastien, Pitsch, Aurélia, Annane, Djillali, Azoulay, Elie, Mekontso Dessap, Armand, Rodriguez, Christophe, Pawlotsky, Jean-Michel, and Fourati, Slim

Published
2022
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39. Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity

Author

Chloé Loyer, Arnaud Lapostolle, Tomas Urbina, Alexandre Elabbadi, Jean-Rémi Lavillegrand, Thomas Chaigneau, Coraly Simoes, Julien Dessajan, Cyrielle Desnos, Mélanie Morin-Brureau, Yannick Chantran, Pierre Aucouturier, Bertrand Guidet, Guillaume Voiriot, Hafid Ait-Oufella, and Carole Elbim

Subjects
COVID-19, Neutrophil, Oxidative burst, Angiogenic neutrophils, Vascular inflammation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. Methods By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2-negative patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. Results At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets—both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide. Moreover patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. Conclusions These data suggest that neutrophil exhaustion may be involved in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome. Graphic Abstract

Published
2022
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40. The COMPASS-COVID-19-ICU Study: Identification of Factors to Predict the Risk of Intubation and Mortality in Patients with Severe COVID-19

Author

Grigoris T. Gerotziafas, Patrick Van Dreden, Douglas D. Fraser, Guillaume Voiriot, Maitray A. Patel, Mark Daley, Alexandre Elabbadi, Aurélie Rousseau, Yannis Prassas, Matthieu Turpin, Marina Marchetti, Loula Papageorgiou, Evangelos Terpos, Meletios A. Dimopoulos, Anna Falanga, Jawed Fareed, Muriel Fartoukh, and Ismail Elalamy

Subjects
COVID-19, hypercoagulability, risk assessment, endothelial cell, inflammation, Medicine
Abstract

In some patients, SARS-CoV-2 infection induces cytokine storm, hypercoagulability and endothelial cell activation leading to worsening of COVID-19, intubation and death. Prompt identification of patients at risk of intubation is an urgent need. Objectives. To derive a prognostic score for the risk of intubation or death in patients with COVID-19 admitted in intensive care unit (ICU), by assessing biomarkers of hypercoagulability, endothelial cell activation and inflammation and a large panel of clinical analytes. Design, Setting and Participants. A prospective, observational study enrolled 118 patients with COVID-19 admitted in the ICU. On the first day of ICU admission, all patients were assessed for biomarkers (protein C, protein S, antithrombin, D-Dimer, fibrin monomers, FVIIa, FV, FXII, FXII, FVIII, FvW antigen, fibrinogen, procoagulant phospholipid dependent clotting time, TFPI, thrombomodulin, P-selectin, heparinase, microparticles exposing TF, IL-6, complement C3a, C5a, thrombin generation, PT, aPTT, hemogram, platelet count) and clinical predictors. Main Outcomes and Measures. The clinical outcomes were intubation and mortality during hospitalization in ICU. Results: The intubation and mortality rates were 70% and 18%, respectively. The COMPASS-COVID-19-ICU score composed of P-Selectin, D-Dimer, free TFPI, TF activity, IL-6 and FXII, age and duration of hospitalization predicted the risk of intubation or death with high sensitivity and specificity (0.90 and 0.92, respectively). Conclusions and Relevance. COVID-19 is related to severe endothelial cell activation and hypercoagulability orchestrated in the context of inflammation. The COMPASS-COVID-19-ICU risk assessment model is accurate for the evaluation of the risk of mechanical ventilation and death in patients with critical COVID-19. The COMPASS-COVID-19-ICU score is feasible in tertiary hospitals and could be placed in the diagnostic procedure of personalized medical management and prompt therapeutic intervention.

Published
2022
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41. Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial

Author

Antoine Monsel, Caroline Hauw-Berlemont, Miryam Mebarki, Nicholas Heming, Julien Mayaux, Otriv Nguekap Tchoumba, Jean-Luc Diehl, Alexandre Demoule, Djillali Annane, Clémence Marois, Sophie Demeret, Emmanuel Weiss, Guillaume Voiriot, Muriel Fartoukh, Jean-Michel Constantin, Bruno Mégarbane, Gaëtan Plantefève, Stéphanie Malard-Castagnet, Sonia Burrel, Michelle Rosenzwajg, Nicolas Tchitchek, Hélène Boucher-Pillet, Guillaume Churlaud, Audrey Cras, Camille Maheux, Chloé Pezzana, Mamadou Hassimiou Diallo, Jacques Ropers, Philippe Menasché, Jérôme Larghero, and APHP STROMA–CoV-2 Collaborative Research Group

Subjects
Severe acute respiratory syndrome coronavirus-2, Acute respiratory distress syndrome, Umbilical cord-derived mesenchymal stromal cells, Good-manufacturing practice, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS–CoV-2-induced ARDS. Methods This multicentre, double-blind, randomized, placebo-controlled trial (STROMA–CoV-2) recruited adults (≥ 18 years) with SARS–CoV-2-induced early (

Published
2022
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42. Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study

Author

Anahita Rouzé, Elise Lemaitre, Ignacio Martin-Loeches, Pedro Povoa, Emili Diaz, Rémy Nyga, Antoni Torres, Matthieu Metzelard, Damien Du Cheyron, Fabien Lambiotte, Fabienne Tamion, Marie Labruyere, Claire Boulle Geronimi, Charles-Edouard Luyt, Martine Nyunga, Olivier Pouly, Arnaud W. Thille, Bruno Megarbane, Anastasia Saade, Eleni Magira, Jean-François Llitjos, Iliana Ioannidou, Alexandre Pierre, Jean Reignier, Denis Garot, Louis Kreitmann, Jean-Luc Baudel, Guillaume Voiriot, Gaëtan Plantefeve, Elise Morawiec, Pierre Asfar, Alexandre Boyer, Armand Mekontso-Dessap, Demosthenes Makris, Christophe Vinsonneau, Pierre-Edouard Floch, Clémence Marois, Adrian Ceccato, Antonio Artigas, Alexandre Gaudet, David Nora, Marjorie Cornu, Alain Duhamel, Julien Labreuche, Saad Nseir, and the coVAPid study group

Subjects
Invasive pulmonary aspergillosis, Severe influenza, COVID-19, Mechanical ventilation, Intensive care unit, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p

Published
2022
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43. Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study

Author

Nicolas Massart, Virginie Maxime, Pierre Fillatre, Keyvan Razazi, Alexis Ferré, Pierre Moine, Francois Legay, Guillaume Voiriot, Marlene Amara, Francesca Santi, Saad Nseir, Stephanie Marque-Juillet, Rania Bounab, Nicolas Barbarot, Fabrice Bruneel, Charles-Edouard Luyt, and the COVID ICU Bacteremia Study Group on behalf of the COVID-ICU Investigators

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. Patients and methods We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. Results Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05–1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. Conclusion COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.

Published
2021
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44. Nationwide retrospective study of critically ill adults with sickle cell disease in France

Author

Maïté Agbakou, Armand Mekontso-Dessap, Morgane Pere, Guillaume Voiriot, Muriel Picard, Jérémy Bourenne, Stephan Ehrmann, Emmanuel Canet, Alexandre Boyer, Saad Nseir, Fabienne Tamion, Arnaud W. Thille, Laurent Argaud, Emmanuel Pontis, Jean-Pierre Quenot, Francis Schneider, Arnaud Hot, Gilles Capellier, Cécile Aubron, Keyvan Razazi, Agathe Masseau, Noëlle Brule, Jean Reignier, and Jean-Baptiste Lascarrou

Subjects
Medicine, Science
Abstract

Abstract Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015–2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval [95% CI], 13.3%–19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio [aOR], 0.98; 95% CI 0.95–0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05–1.14; p

Published
2021
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45. Transesophageal echocardiography for cardiovascular risk estimation in patients with sepsis and new-onset atrial fibrillation: a multicenter prospective pilot study

Author

Vincent Labbé, Stephane Ederhy, Nathanael Lapidus, Jérémie Joffre, Keyvan Razazi, Laurent Laine, Oumar Sy, Sebastian Voicu, Frank Chemouni, Nadia Aissaoui, Roland Smonig, Denis Doyen, Fabrice Carrat, Guillaume Voiriot, Armand Mekontso-Dessap, Ariel Cohen, Muriel Fartoukh, and for the FAST Study Group

Subjects
Atrial fibrillation, Transesophageal echocardiography, Stroke, Bleeding, Sepsis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Echocardiographic parameters have been poorly investigated for estimating cardiovascular risk in patients with sepsis and new-onset atrial fibrillation. We aim to assess the prevalence of transesophageal echocardiographic abnormalities and their relationship with cardiovascular events in mechanically ventilated patients with sepsis and new-onset atrial fibrillation. Methods In this prospective multicenter pilot study, left atrial/left atrial appendage (LA/LAA) dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were assessed using an initial transesophageal echocardiographic study, which was repeated after 48–72 h to detect LA/LAA thrombus formation. The study outcome was a composite of cardiovascular events at day 28, including arterial thromboembolic events (ischemic stroke, non-cerebrovascular arterial thromboembolism, LA/LAA thrombus), major bleeding, and all-cause death. Results The study population comprised 94 patients (septic shock 63%; 35% women; median age 69 years). LA/LAA dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were detected in 17 (19%), 22 (24%), and 27 (29%) patients, respectively. At day 28, the incidence of cardiovascular events was 46% (95% confidence interval [CI]: 35 to 56). Arterial thromboembolic events and major bleeding occurred in 7 (7%) patients (5 ischemic strokes, 1 non-cerebrovascular arterial thromboembolism, 2 left atrial appendage thrombi) and 18 (19%) patients, respectively. At day 28, 27 patients (29%) died. Septic shock (hazard ratio [HR]: 2.36; 95% CI 1.06 to 5.29) and left ventricular systolic dysfunction (HR: 2.06; 95% CI 1.05 to 4.05) were independently associated with cardiovascular events. Conclusions Transesophageal echocardiographic abnormalities are common in mechanically ventilated patients with sepsis and new-onset atrial fibrillation, but only left ventricular systolic dysfunction was associated with cardiovascular events at day 28.

Published
2021
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46. Non–C. difficile Clostridioides Bacteremia in Intensive Care Patients, France

Author

Guillaume Morel, Guillaume Mulier, Etienne Ghrenassia, Moustafa Abdel Nabey, Yacine Tandjaoui, Achille Kouatchet, Laura Platon, Frédéric Pène, Anne-Sophie Moreau, Amelie Seguin, Damien Contou, Romain Sonneville, David Rousset, Muriel Picard, Guillaume Dumas, Djamel Mokart, Bruno Megarbane, Guillaume Voiriot, Isabelle Oddou, Elie Azoulay, Lucie Biard, and Lara Zafrani

Subjects
Clostridium, Clostridioides, bacteremia, ICU, intensive care, hemolysis, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Usually responsible for soft tissue infections, Clostridioides species can also cause bacteremia, life-threatening infections often requiring intensive care unit (ICU) admission. We conducted a multicenter retrospective study to investigate Clostridioides bacteremia in ICUs to describe the clinical and biologic characteristics and outcomes in critically ill patients. We identified 135 patients with Clostridioides bacteremia, which occurred almost exclusively (96%) in patients with underlying conditions. Septic shock and digestive symptoms were the hallmarks of Clostridioides bacteremia in the ICU. We identified 16 different species of Clostridioides, among which C. perfringens accounted for 31% of cases. Despite the high sensitivity of Clostridioides to common antimicrobial drugs, mortality rates were high: 52% for ICU patients and 71% overall at 3 months. In multivariate analysis, the most important factor associated with increased risk for death was the presence of hemolysis. Clostridioides bacteremia often leads to multiple organ failures, which have high mortality rates.

Published
2021
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47. Energetic dysfunction in sepsis: a narrative review

Author

Sebastien Preau, Dominique Vodovar, Boris Jung, Steve Lancel, Lara Zafrani, Aurelien Flatres, Mehdi Oualha, Guillaume Voiriot, Youenn Jouan, Jeremie Joffre, Fabrice Huel, Nicolas De Prost, Stein Silva, Eric Azabou, and Peter Radermacher

Subjects
Energetic dysfunction, Metabolism, Mitochondria, Mitochondrial dysfunction, Organ dysfunction, Sepsis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions. Main text Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described. Conclusions Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.

Published
2021
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48. Seasonal burden of severe influenza virus infection in the critically ill patients, using the Assistance Publique-Hôpitaux de Paris clinical data warehouse: a pilot study

Author

Muriel Fartoukh, Guillaume Voiriot, Laurent Guérin, Jean Damien Ricard, Alain Combes, Morgane Faure, Sarah Benghanem, Etienne de Montmollin, Yacine Tandjaoui-Lambiotte, Antoine Vieillard-Baron, Eric Maury, Jean-Luc Diehl, Keyvan Razazi, Virginie Lemiale, Pierre Trouiller, Benjamin Planquette, Laurent Savale, Nicholas Heming, Jonathan Marey, AP-HP Clinical Data Warehouse, Fabrice Carrat, Nathanael Lapidus, and The EPIcuFLU_APHP Group

Subjects
Epidemic, Influenza, Assistance Publique-Hôpitaux de Paris (AP-HP) clinical data warehouse, Critical care, Prognosis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Purpose At the critical care level, the flu surveillance system is limited in France, with heterogeneous regional modalities of implementation. Materials, patients and methods We aimed at assessing the relevance of the Assistance Publique-Hôpitaux de Paris (AP-HP) clinical data warehouse for estimating the burden of the influenza epidemic on medical adult critical care units of the AP-HP, and outcome of patients during the flu season 2017–2018. This exploratory multi-site epidemiological study comprised all consecutive adult stays (n = 320) in 18 medical intensive care units (ICU) or intermediate care wards (ICW) for probable or confirmed Influenza virus infection during the 2017–2018 flu season. Results Patients admitted to ICU/ICW had low vaccination coverage (21%), required life support in 60% of cases, stayed in the ICU for a median of 8 days, and had high 28-day mortality rate (19.7%; 95% confidence interval 15.5–24.5). Early prognostic factors included age, core temperature, the acute organ failures score, and the early administration of antiviral therapy. Conclusions Data directly extracted from the electronic medical records stored in the data warehouse provide detailed clinical, care pathway and prognosis information. The real-time availability should enable to detect and assess the burden of the most severe cases. By a firmer and more acute monitoring and adjustment of care and patient management, hospitals could generate more ICU/ICW capacities, sensitize their emergency department and contribute to the recommendations from health authorities. This pilot study is of particular relevance in the context of emerging epidemics of severe acute respiratory diseases.

Published
2021
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