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23,834 results on '"New York University School of Medicine"'

1. Web Alert

Author

Edwin Chan, MD Department of Medicine/Clinical Pharmacology, New York University School of Medicine, New Bellevue Hospital, 16N1, 550 First Avenue, New York, NY 10016, USA. E-mail: chane01@nyu.edu

Published
2007
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2. Fast optical tracking of diffusion in brain extracellular space

Author

Nathan S. Kline Institute, New York University School of Medicine, Universität Leipzig, Hrabe, Jan, Hrabetova, Sabina, Nathan S. Kline Institute, New York University School of Medicine, Universität Leipzig, Hrabe, Jan, and Hrabetova, Sabina

Published
2016

3. Measurement of local diffusion properties in brain tissue

Author

New York University School of Medicine, Universität Leipzig, Nicholson, Charles, Tao, Lian, Hrabetova, Sabina, Thorne, Robert G., New York University School of Medicine, Universität Leipzig, Nicholson, Charles, Tao, Lian, Hrabetova, Sabina, and Thorne, Robert G.

Published
2016

5. Modeling brain extracellular space from diffusion data

Author

New York University School of Medicine, Universität Leipzig, Nicholson, Charles, New York University School of Medicine, Universität Leipzig, and Nicholson, Charles

Abstract

The extracellular space (ECS) of the brain is a thin region surrounding each cell that is filled with a medium resembling cerebrospinal fluid and an unknown amount of extracellular matrix. The ECS is difficult to study but diffusion measurements based on a point-source diffusion paradigm have begun to reveal the complex structure of this region. Despite the complexity, a modified version of Fick’s classical diffusion equation incorporating parameters for volume fraction and tortuosity has been shown to be valid. Using real-time iontophoresis and the small molecule tetramethylammonium, the volume fraction of typical brain tissue has been determined to be 0.2, i.e. 20% of the brain is ECS and the typical tortuosity is 1.6, which means that a small molecule has an effective diffusion coefficient that is 2.6 less than in free solution. Monte Carlo modeling, however, shows that a simple ensemble of convex cells, each surrounded by a uniform ECS cannot generate a tortuosity greater than 1.225. Further modeling suggests that the discrepancy between experiments and theory may be accounted for by the existence of dead-space microdomains in the ECS; a viscous extracellular matrix might also play a role. Diffusion measurements with integrative optical imaging of fluorescent macromolecules and quantum dots show that tortuosity is increased with macromolecular size and analysis based on the theory of restricted diffusion in pores suggests that the width of the ECS is in the range 38-64 nm.

Published
2016

6. Immune Response and Restoration: Where Are We Now; Where Are We Going?

Author

New York University. School of Medicine, New York University. School of Medicine, New York University. School of Medicine, and New York University. School of Medicine

Abstract

(DLPS) 5571095.0171.015, http://name.umdl.umich.edu/5571095.0171.015, http://quod.lib.umich.edu/t/text/accesspolicy.html, Where applicable, subject to copyright. Other restrictions on distribution may apply. Please go to http://www.umdl.umich.edu/ for more information.

Published
2002

7. Immune Response and Restoration: Where are We Now; Where are We going? [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

Author

New York University. School of Medicine, New York University. School of Medicine, New York University. School of Medicine, and New York University. School of Medicine

Abstract

(DLPS) 5571095.0171.043, http://name.umdl.umich.edu/5571095.0171.043, http://quod.lib.umich.edu/t/text/accesspolicy.html, Where applicable, subject to copyright. Other restrictions on distribution may apply. Please go to http://www.umdl.umich.edu/ for more information.

Published
2002

11. Prevention Our Future [Conference on Advances in AIDS Vaccines and Meeting of the National Cooperative Vaccine Development Groups for AIDS (8th: 1996: Bethesda, Maryland)]

Author

New York University. School of Medicine, New York University. School of Medicine, New York University. School of Medicine, and New York University. School of Medicine

Abstract

(DLPS) 5571095.0108.021, http://name.umdl.umich.edu/5571095.0108.021, http://quod.lib.umich.edu/t/text/accesspolicy.html, Where applicable, subject to copyright. Other restrictions on distribution may apply. Please go to http://www.umdl.umich.edu/ for more information.

Published
1996

12. ??-Endorphin expression in the mouse retina

Author

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA, Department of Ophthalmology, New York University School of Medicine, New York, New York 10016, USA, Department of Neurobiology and Genetics, IGBMC, CNRS UMR 7104, Inserm U 964, Universit?? de Strasbourg, F-67404 Illkirch, France, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA ; Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, Gallagher, Shannon K., Witkovsky, Paul, Roux, Michel J., Low, Malcolm J., Otero-Corchon, Veronica, Hentges, Shane T., Vigh, Jozsef, Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA, Department of Ophthalmology, New York University School of Medicine, New York, New York 10016, USA, Department of Neurobiology and Genetics, IGBMC, CNRS UMR 7104, Inserm U 964, Universit?? de Strasbourg, F-67404 Illkirch, France, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA ; Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, Gallagher, Shannon K., Witkovsky, Paul, Roux, Michel J., Low, Malcolm J., Otero-Corchon, Veronica, Hentges, Shane T., and Vigh, Jozsef

Abstract

Evidence showing expression of endogenous opioids in the mammalian retina is sparse. In the present study we examined a transgenic mouse line expressing an obligate dimerized form of Discosoma red fluorescent protein (DsRed) under the control of the pro-opiomelanocortin promoter and distal upstream regulatory elements to assess whether pro-opiomelanocortin peptide (POMC), and its opioid cleavage product, ??-endorphin, are expressed in the mouse retina. Using double label immunohistochemistry we found that DsRed fluorescence was restricted to a subset of GAD-67-positive cholinergic amacrine cells of both orthotopic and displaced subtypes. About 50% of cholinergic amacrine cells colocalized DsRed and a large fraction of DsRed-expressing amacrine cells was positive for ??-endorphin immunostaining, whereas ??-endorphin-immunoreactive neurons were absent in retinas of POMC null mice. Our findings contribute to a growing body of evidence demonstrating that opioid peptides are an integral component of vertebrate retinas, including those of mammals. J. Comp. Neurol. 518:3130???3148, 2010. ?? 2010 Wiley-Liss, Inc.

Published
2010

13. Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome

Author

Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA, Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA ; Paul H. Dekruif Professor of Pathology, University of Michigan Medical School, 1500 E. Medical Center Dr, 4215 CCGC, Ann Arbor, MI 48109, USA Fax: +1-734-647-9654, Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Immunology Institute, Osaka University, Osaka, Japan, Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Immunology Institute, Osaka University, Osaka, Japan ; Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan, Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan, Department of Medical Parasitology, New York University School of Medicine, New York, NY, USA, Reimer, Thornik, Shaw, Michael H., Franchi, Luigi, Coban, Cevayir, Ishii, Ken J., Akira, Shizuo, Horii, Toshihiro, Rodriguez, Ana, N????ez, Gabriel, Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA, Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA ; Paul H. Dekruif Professor of Pathology, University of Michigan Medical School, 1500 E. Medical Center Dr, 4215 CCGC, Ann Arbor, MI 48109, USA Fax: +1-734-647-9654, Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Immunology Institute, Osaka University, Osaka, Japan, Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Immunology Institute, Osaka University, Osaka, Japan ; Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan, Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan, Department of Medical Parasitology, New York University School of Medicine, New York, NY, USA, Reimer, Thornik, Shaw, Michael H., Franchi, Luigi, Coban, Cevayir, Ishii, Ken J., Akira, Shizuo, Horii, Toshihiro, Rodriguez, Ana, and N????ez, Gabriel

Abstract

Cerebral malaria is the most severe complication of Plasmodium falciparum infection in humans and the pathogenesis is still unclear. Using the P. berghei ANKA infection model of mice, we investigated a potential involvement of Nlrp3 and the inflammasome in the pathogenesis of cerebral malaria. Nlrp3 mRNA expression was upregulated in brain endothelial cells after exposure to P. berghei ANKA. Although ??-hematin, a synthetic compound of the parasites heme polymer hemozoin, induced the release of IL-1?? in macrophages through Nlrp3, we did not obtain evidence for a role of IL-1?? in vivo . Nlrp3 knock-out mice displayed a delayed onset of cerebral malaria; however, mice deficient in caspase-1, the adaptor protein ASC or the IL-1 receptor succumbed as WT mice. These results indicate that the role of Nlrp3 in experimental cerebral malaria is independent of the inflammasome and the IL-1 receptor pathway.

Published
2010

14. ＜Symposium IV＞Cerebral amyloid angiopathy and Alzheimer's disease

Author

Department of Pathology, New York University School of Medicine, Department of Clinical Sciences, Tsukuba University, Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Ghiso, Jorge, Tomidokoro, Yasushi, Revez, Tamas, Frangione, Blas, Rostagno, Agueda, Department of Pathology, New York University School of Medicine, Department of Clinical Sciences, Tsukuba University, Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Ghiso, Jorge, Tomidokoro, Yasushi, Revez, Tamas, Frangione, Blas, and Rostagno, Agueda

Abstract

Cerebral amyloid angiopathy （CAA） is increasingly recognized as a major contributor of Alzheimer’s disease（ AD） pathogenesis. To date, vascular deposits and not parenchymal plaques appear more sensitive predictors of dementia. Amyloid deposition in and around cerebral blood vessels plays a central role in a series of response mechanisms that lead to changes in the integrity of the blood-brain barrier, extravasations of plasma proteins, edema formation, release of inflammatory mediators and matrix metalloproteases which, in turn, produce partial degradation of the basal lamina with the potential to develop hemorrhagic complications. The progressive buildup of amyloid deposits in and around blood vessels chronically limits blood supply and causes focal deprivation of oxygen, triggering a secondary cascade of metabolic events several of which involve the generation of nitrogen and oxygen free radicals with consequent oxidative stress and cell toxicity. Many aspects of CAA in early- and lateonset AD ‒the special preference of Aβ40 to deposit in the vessel walls, the favored vascular compromise associated with many Aβ genetic variants, the puzzling observation that some of these vasculotropic variants solely manifest with recurrent hemorrhagic episodes while others are mainly associated with dementia‒ await clarifi cation. Non-Aβ cerebral amyloidoses reinforce the viewpoint that plaque burden is not indicative of dementia while highlighting the relevance of non-fi brillar lesions and vascular involvement in the disease pathogenesis. The lessons learned from the comparative study of Aβ and non-Aβ cerebral amyloidosis provide new avenues and alternative models to study the role of amyloid in the molecular basis of neurodegeneration.

Published
2010

15. Interobserver reliability of computed tomography-derived primary tumor volume measurement in patients with supraglottic carcinoma

Author

Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan ; Department of Otolaryngology/Head Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan ; Fax: (734) 764-2412 ; Department of Radiology, B2A209, University of Michigan Health Systems, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0030, Center for Statistical Sciences, Brown University, Providence, Rhode Island, Department of Radiology, State University of New York, Albany Medical School, Albany, New York, Department of Radiology, University of Florida College of Medicine, Gainesville, Florida, Department of Radiation Oncology, New York University School of Medicine, New York, New York, Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida, Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, Department of Radiology, Bryn Mawr Hospital, Bryn Mawr, Pennsylvania, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, Mukherji, Suresh K., Toledano, Alicia Y., Beldon, Clifford, Schmalfuss, Ilona M., Cooper, Jay S., Sicks, JoRean D., Amdur, Robert, Sailer, Scott, Loevner, Laurie A., Kousouboris, Phil, Ang, Kian, Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan ; Department of Otolaryngology/Head Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan ; Fax: (734) 764-2412 ; Department of Radiology, B2A209, University of Michigan Health Systems, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0030, Center for Statistical Sciences, Brown University, Providence, Rhode Island, Department of Radiology, State University of New York, Albany Medical School, Albany, New York, Department of Radiology, University of Florida College of Medicine, Gainesville, Florida, Department of Radiation Oncology, New York University School of Medicine, New York, New York, Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida, Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, Department of Radiology, Bryn Mawr Hospital, Bryn Mawr, Pennsylvania, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, Mukherji, Suresh K., Toledano, Alicia Y., Beldon, Clifford, Schmalfuss, Ilona M., Cooper, Jay S., Sicks, JoRean D., Amdur, Robert, Sailer, Scott, Loevner, Laurie A., Kousouboris, Phil, and Ang, Kian

Abstract

BACKGROUND Prior studies have determined that macroscopic ("gross") tumor volume (GTV), as calculated from pretreatment computer tomography (CT), was capable of predicting local control in squamous cell carcinoma arising in different subsites in the head and neck in patients who were treated with nonsurgical organ-preservation therapy. The majority of these studies were single-institution, retrospective investigations. Consequently, there has been concern that GTV measurements may not be reproducible by different readers at different institutions. The objective of the current study was to measure the interobserver reliability for GTV measurements for squamous cell carcinoma of the supraglottic larynx (SGSCCA) performed by different readers at different institutions. METHODS Eight experienced readers (4 neuroradiologists and 4 radiation oncologists) from different institutions independently measured the pretreatment GTV of 20 patients with SGSCCA. The CT scans were obtained from patients entered into the definitive radiation therapy arm of Radiation Therapy Oncology Group protocol 91-11, who had supraglottic carcinoma and underwent pretreatment CT scans of the neck. Statistical analysis focused on interobserver reliability as measured by the intraclass correlation coefficient. RESULTS The intraclass correlation coefficient was 0.81 (95% lower confidence bound, 0.71). This value was interpreted as "excellent." CONCLUSIONS GTV measurements were reliable and reproducible when performed by neuroradiologists and radiation oncologists who were experienced in the interpretation of CT scans of the extracranial head and neck in patients with SGSCCA. The result implied that the correlation between GTV and local control should be reproducible across institutions. Cancer 2005. © 2005 American Cancer Society.

Published
2006

16. Paradoxical decrease in norepinephrine content of adult mouse spleen and heart after neonatal nerve growth factor treatment

Author

Department of Psychiatry, Mental Health Research Institute, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A., Department of Biological Chemistry, School of Medicine, University of California, Los Angeles., Department of Psychiatry, New York University School of Medicine, New York, Campbell, Robert J., Wilson, Linda G.M., Herschman, Harvey R., DiCara, Leo V., Stone, Eric A., Department of Psychiatry, Mental Health Research Institute, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A., Department of Biological Chemistry, School of Medicine, University of California, Los Angeles., Department of Psychiatry, New York University School of Medicine, New York, Campbell, Robert J., Wilson, Linda G.M., Herschman, Harvey R., DiCara, Leo V., and Stone, Eric A.

Published
2006

17. An epigenetic switch controls an alternative NR2F2 isoform 2 that unleashes a metastatic program in melanoma

Author

Davalos, Verónica, Lovell, Claudia, von Itter, Richard, Dolgalev, Igor, Agrawal, Praveen, Baptiste, Gillian, Kahler, David, Sokolova, Elena, Moran, Sebastian, Piqué, Laia, Vega-Saenz de Miera, Eleazar, Fontanals-Cirera, Barbara, Karz, Alcida, Tsirigos, Aristotelis, Yun, Chi, Darvishian, Farbod, Etchevers, Heather, Osman, Iman, Esteller, Manel, Schober, Markus, Hernando, Eva, Department of Pathology, New York University Grossman School of Medicine, NY 10016, USA, Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, NY 10016, USA, Bellvitge Biomedical Research Institute, Partenaires INRAE, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain, New York University School of Medicine (NYU Grossman School of Medicine), National Tsing Hua University [Hsinchu] (NTHU), City University of Hong Kong [Hong Kong] (CUHK), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Marseille Maladies Rares (MarMaRa), Aix Marseille Université (AMU), Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, NY 10016, USA (NYUSM), Institució Catalana de Recerca i Estudis Avançats (ICREA), Josep Carreras Leukaemia Research Institute (IJC), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Universitat de Barcelona (UB), New York University [New York] (NYU), NYU System (NYU), and We thank the NYU Experimental Pathology Core, the NYU Genome Technology Center, the NYUCenter for Biospecimen Research and Development, and the Small Animal Imaging core, all partially supported by the Laura and Isaac Perlmutter Cancer Center Support Grant (CCSG) NIH/NCI P30CA016087 (NIH/NCI), and National Institute of Health S10 Grants NIH/ORIP S10OD01058 and S10OD018338. We thank the High Throughput Biology Core partially funded by P30CA16087 and NYSTEM Contract C026719. V.D. was supported by the People Program (Marie Curie Actions) of the European Union's Seventh Framework Program (FP7-PEOPLE30 2013-IOF) under REA grant agreement n° PIOF-GA-2013-623443. This work was funded by NCI/NIH R01CA202027, R01CA274100, P01CA206980 and NYU Melanoma SPOREP50CA225450 (PI: I.O).

Subjects
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; Metastatic melanoma develops once transformed melanocytic cells begin to de-differentiate into migratory and invasive melanoma cells with neural crest cell (NCC)-like and epithelial-tomesenchymal transition (EMT)-like features. However, it is still unclear how transformed melanocytes assume a metastatic melanoma cell state. Here, we define DNA methylation changes that accompany metastatic progression in melanoma patients and discover Nuclear Receptor Subfamily 2 Group F, Member 2 – isoform 2 (NR2F2-Iso2) as an epigenetically regulated metastasis driver. NR2F2-Iso2 is transcribed from an alternative transcriptional start site (TSS) and it is truncated at the N-terminal end which encodes the NR2F2 DNA-bindingdomain. We find that NR2F2-Iso2 expression is turned off by DNA methylation when NCCs differentiate into melanocytes. Conversely, this process is reversed during metastatic melanoma progression, when NR2F2-Iso2 becomes increasingly hypomethylated and re-expressed. Our functional and molecular studies suggest that NR2F2-Iso2 drives metastatic melanomaprogression by modulating the activity of full-length NR2F2 (Isoform 1) over EMT- and NCC-associated target genes. Our findings indicate that DNA methylation changes play a crucial role during metastatic melanoma progression, and their control of NR2F2 activity allows transformed melanocytes to acquire NCC-like and EMT-like features. This epigenetically regulated transcriptional plasticity facilitates cell state transitions and metastatic spread.

Published
2023

18. Loss of glucocorticoid receptor phosphorylation contributes to cognitive and neurocentric damages of the amyloid-β pathway

Author

Yann Dromard, Margarita Arango-Lievano, Amelie Borie, Maheva Dedin, Pierre Fontanaud, Joan Torrent, Michael J. Garabedian, Stephen D. Ginsberg, Freddy Jeanneteau, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), New York University School of Medicine (NYU Grossman School of Medicine), Nathan Kline Institute, BioCampus (BCM), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Nathan S. Kline Institute for Psychiatric Research (NKI), New York State Office of Mental Health, Guerineau, Nathalie C., and freddy, jeanneteau

Subjects
Hydrocortisone, [SDV]Life Sciences [q-bio], Mice, Transgenic, Neuroimaging, Glucocorticoid receptor, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, Amyloid beta-Protein Precursor, Mice, Cognition, Receptors, Glucocorticoid, Alzheimer Disease, Memory, Animals, Humans, Receptor, trkB, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Phosphorylation, Amyloid beta-Peptides, Brain-Derived Neurotrophic Factor, Spine dynamics, [SDV] Life Sciences [q-bio], Disease Models, Animal, BDNF, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical)
Abstract

International audience; AbstractAberrant cortisol and activation of the glucocorticoid receptor (GR) play an essential role in age-related progression of Alzheimer's disease (AD). However, the GR pathways required for influencing the pathobiology of AD dementia remain unknown. To address this, we studied an early phase of AD-like progression in the well-established APP/PS1 mouse model combined with targeted mutations in the BDNF-dependent GR phosphorylation sites (serines 134/267) using molecular, behavioral and neuroimaging approaches. We found that disrupting GR phosphorylation (S134A/S267A) in mice exacerbated the deleterious effects of the APP/PS1 genotype on mortality, neuroplasticity and cognition, without affecting either amyloid-β deposition or vascular pathology. The dynamics, maturation and retention of task-induced new dendritic spines of cortical excitatory neurons required GR phosphorylation at the BDNF-dependent sites that amyloid-β compromised. Parallel studies in postmortem human prefrontal cortex revealed AD subjects had downregulated BDNF signaling and concomitant upregulated cortisol pathway activation, which correlated with cognitive decline. These results provide key evidence that the loss of neurotrophin-mediated GR phosphorylation pathway promotes the detrimental effects of the brain cortisol response that contributes to the onset and/or progression of AD dementia. These findings have important translational implications as they provide a novel approach to treating AD dementia by identifying drugs that increase GR phosphorylation selectively at the neurotrophic sites to improve memory and cognition.

Published
2022

19. Gender bias in academia: A lifetime problem that needs solutions

Author

Adrienne L. Fairhall, Rosa Dominguez-Faus, Nancy Kopell, Ilina Bhaya-Grossman, Brooke Staveland, Katarina Slama, Mark A. Gorenstein, Robert T. Knight, Richard Jimenez, Joni D. Wallis, Athina Tzovara, Pedro Pinheiro-Chagas, Jack J. Lin, Ignacio Saez, Dylan Riley, Maria Ivanova, Yvonne M. Fonken, Ivan Skelin, Chris Holdgraf, Déborah Marciano, Julia W. Y. Kam, Celeste Kidd, Danielle S. Bassett, Nicholas E. Myers, Adeen Flinker, Zachariah R. Cross, Soyeon Jun, Anaïs Llorens, Enitan T Marcelle, Anna C. Nobre, Anat Perry, Sabine Kastner, Stephanie Martin, Shlomit Yuval-Greenberg, Karita E. Ojala, Nina F. Dronkers, Laura J. Kray, Colin W. Hoy, Stephanie K. Riès, William K. Chang, Aurélie Bidet-Caulet, Ludovic Bellier, Xiao Jing Wang, Anne Kristin Solbakk, Elizabeth A. Buffalo, University of California [Berkeley] (UC Berkeley), University of California (UC), University of Bern, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of South Australia [Adelaide], University of California [Davis] (UC Davis), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Oxford, Seoul National University [Seoul] (SNU), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), The Hebrew University of Jerusalem (HUJ), Stanford University, San Diego State University (SDSU), University of California [Irvine] (UC Irvine), University of Pennsylvania, University of Washington [Seattle], Boston University [Boston] (BU), University of Oslo (UiO), New York University [New York] (NYU), NYU System (NYU), Tel Aviv University (TAU), Princeton University, Otten, Lisa, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Llorens, Anaïs, Tzovara, Athina, Bellier, Ludovic, Bhaya-Grossman, Ilina, Cross, Zachariah R, and Dronkers, Nina F

Subjects
Gender Equity, Male, academic institutions, Gender equity, Universities, Inequality, media_common.quotation_subject, Sexism, MEDLINE, gender equity, Article, Gender bias, Psychology, Humans, 000 Informatik, Wissen, Systeme, ComputingMilieux_MISCELLANEOUS, media_common, Neurology & Neurosurgery, Research, [SCCO.NEUR]Cognitive science/Neuroscience, General Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Neurosciences, 510 Mathematik, [SHS.GENRE] Humanities and Social Sciences/Gender studies, Mental health, Research Personnel, Brain Disorders, Mental Health, Good Health and Well Being, Balance (accounting), Cognitive Sciences, Female, Demographic economics, Generic health relevance, 610 Medizin und Gesundheit, [SHS.GENRE]Humanities and Social Sciences/Gender studies, Diversity (politics)
Abstract

International audience; Despite increased awareness of the lack of gender equity in academia and a growing number of initiatives to address issues of diversity, change is slow, and inequalities remain. A major source of inequity is gender bias, which has a substantial negative impact on the careers, work-life balance, and mental health of underrepresented groups in science. Here, we argue that gender bias is not a single problem but manifests as a collection of distinct issues that impact researchers’ lives. We disentangle these facets and propose concrete solutions that can be adopted by individuals, academic institutions, and society

Published
2021

20. Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author

Boris Novakovic, Andreas Schlitzer, Giuseppe Matarese, Zahi A. Fayad, Willem J. M. Mulder, Henk Stunnenberg, Andrew R. DiNardo, Niels P. Riksen, Joachim L. Schultze, Christine Stabell Benn, Joseph C. Sun, Eva Kaufmann, Shabaana A. Khader, Michael H. Sieweke, Siroon Bekkering, Stephanie Fanucchi, Luis B. Barreiro, Maziar Divangahi, Mihai G. Netea, Reinout van Crevel, Jordi Ochando, Peter Aaby, Shruti Naik, Leo A. B. Joosten, Triantafyllos Chavakis, Musa M. Mhlanga, Eicke Latz, David L. Williams, Jos W. M. van der Meer, Luke A. J. O'Neill, Ramnik J. Xavier, Nigel Curtis, Robert W. Sauerwein, Kate L. Jeffrey, Edward R. Sherwood, Elaine Fuchs, Sebastian Weis, Nargis Khan, Melanie Hamon, Raphael Duivenwoorden, Keiko Ozato, Simone J.C.F.M. Moorlag, Jorge Domínguez-Andrés, Frank L. van de Veerdonk, Precision Medicine, ICMS Core, McGill University Health Center [Montreal] (MUHC), Bandim Health Project, International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH Network), Washington University in Saint Louis (WUSTL), The University of Chicago Medicine [Chicago], Radboud University Medical Center [Nijmegen], Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Melbourne, Baylor College of Medicine (BCM), Baylor University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Eindhoven University of Technology [Eindhoven] (TU/e), University of Cape Town, Rockefeller University [New York], Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP), Harvard Medical School [Boston] (HMS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Trinity Biomedical Sciences Institute, School of Biochemistry & Immunology, National Institute of Child Health and Human Development [Bethesda], National Institutes of Health, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Universität Bonn = University of Bonn, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biotechnology Center, and Center for Regenerative Therapies Dresden (CRTD), Max Delbrück Centrum für Molekulare Medizin (MDC), University of Southern Denmark (SDU), Radboud University [Nijmegen], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Jena University Hospital [Jena], East Tennessee State University (ETSU), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts Institute of Technology (MIT), Divangahi, M., Aaby, P., Khader, S. A., Barreiro, L. B., Bekkering, S., Chavakis, T., van Crevel, R., Curtis, N., Dinardo, A. R., Dominguez-Andres, J., Duivenwoorden, R., Fanucchi, S., Fayad, Z., Fuchs, E., Hamon, M., Jeffrey, K. L., Khan, N., Joosten, L. A. B., Kaufmann, E., Latz, E., Matarese, G., van der Meer, J. W. M., Mhlanga, M., Moorlag, S. J. C. F. M., Mulder, W. J. M., Naik, S., Novakovic, B., O'Neill, L., Ochando, J., Ozato, K., Riksen, N. P., Sauerwein, R., Sherwood, E. R., Schlitzer, A., Schultze, J. L., Sieweke, M. H., Benn, C. S., Stunnenberg, H., Sun, J., van de Veerdonk, F. L., Weis, S., Williams, D. L., Xavier, R., Netea, M. G., Institut Pasteur [Paris], Consiglio Nazionale delle Ricerche (CNR), University of Bonn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft, Radboud university [Nijmegen], Hamon, Melanie, and ACS - Atherosclerosis & ischemic syndromes

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], animal diseases, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Priming (immunology), Adaptive Immunity, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, ComputingMilieux_MISCELLANEOUS, immunology [BCG Vaccine], Vaccination, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Cell Differentiation, Common framework, [SDV] Life Sciences [q-bio], MESH: BCG Vaccine, BCG Vaccine, MESH: Immunologic Memory, MESH: Immunity, Innate, MESH: Cell Differentiation, MESH: Immune Tolerance, Immunology, education, immunology [Adaptive Immunity], chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, Immune system, Immunity, Immune Tolerance, Animals, Humans, ddc:610, Molecular Biology, MESH: Humans, immunology [Immune Tolerance], Cell Biology, MESH: Vaccination, biochemical phenomena, metabolism, and nutrition, Immunity, Innate, immunology [Immunologic Memory], immunology [Immunity, Innate], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030104 developmental biology, bacteria, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Neuroscience, Immunologic Memory, MESH: Adaptive Immunity, 030215 immunology
Abstract

The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.

Published
2021

21. Secernin-1 is a novel phosphorylated tau binding protein that accumulates in Alzheimer’s disease and not in other tauopathies

Author

Geoffrey Pires, Sacha McElligott, Glenda M. Halliday, Marie-Claude Potier, Eleanor Drummond, Shiron Drusinsky, Thomas Wisniewski, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), The University of Sydney, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CIC Pitié BT, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Neurofibrillary tangles, Pathology, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Nerve Tissue Proteins, tau Proteins, Neuropathology, lcsh:RC346-429, Pathology and Forensic Medicine, Progressive supranuclear palsy, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Protein-protein interaction, Alzheimer Disease, medicine, Humans, Corticobasal degeneration, Phosphorylation, Secernin-1, lcsh:Neurology. Diseases of the nervous system, Aged, 030304 developmental biology, Aged, 80 and over, Cerebral Cortex, 0303 health sciences, business.industry, Phosphorylated tau, Research, Frontotemporal lobar degeneration, Middle Aged, medicine.disease, Tauopathies, Hereditary cerebral hemorrhage with amyloidosis, Immunohistochemistry, Biomarker (medicine), Female, Neurology (clinical), Tauopathy, business, Alzheimer’s disease, 030217 neurology & neurosurgery, Protein Binding
Abstract

We recently identified Secernin-1 (SCRN1) as a novel amyloid plaque associated protein using localized proteomics. Immunohistochemistry studies confirmed that SCRN1 was present in plaque-associated dystrophic neurites and also revealed distinct and abundant co-localization with neurofibrillary tangles (NFTs). Little is known about the physiological function of SCRN1 and its role in Alzheimer’s disease (AD) and other neurodegenerative diseases has not been studied. Therefore, we performed a comprehensive study of SCRN1 distribution in neurodegenerative diseases. Immunohistochemistry was used to map SCRN1 accumulation throughout the progression of AD in a cohort of 58 patients with a range of NFT pathology (Abundant NFT,n = 21; Moderate NFT,n = 22; Low/No NFT,n = 15), who were clinically diagnosed as having AD, mild cognitive impairment or normal cognition. SCRN1 accumulation was also examined in two cases with both Frontotemporal Lobar Degeneration (FTLD)-Tau and AD-related neuropathology, cases of Down Syndrome (DS) with AD (n = 5), one case of hereditary cerebral hemorrhage with amyloidosis – Dutch type (HCHWA-D) and other non-AD tauopathies including: primary age-related tauopathy (PART, [n = 5]), Corticobasal Degeneration (CBD, [n = 5]), Progressive Supranuclear Palsy (PSP, [n = 5]) and Pick’s disease (PiD, [n = 4]). Immunohistochemistry showed that SCRN1 was a neuronal protein that abundantly accumulated in NFTs and plaque-associated dystrophic neurites throughout the progression of AD. Quantification of SCRN1 immunohistochemistry confirmed that SCRN1 preferentially accumulated in NFTs in comparison to surrounding non-tangle containing neurons at both early and late stages of AD. Similar results were observed in DS with AD and PART. However, SCRN1 did not co-localize with phosphorylated tau inclusions in CBD, PSP or PiD. Co-immunoprecipitation revealed that SCRN1 interacted with phosphorylated tau in human AD brain tissue. Together, these results suggest that SCRN1 is uniquely associated with tau pathology in AD, DS and PART. As such, SCRN1 has potential as a novel therapeutic target and could serve as a useful biomarker to distinguish AD from other tauopathies.

Published
2019

22. nucGEMs probe the biophysical properties of the nucleoplasm

Author

Ying Xie, Andrew Bazley, Fred Chang, Joël Lemière, Martina Bonucci, Tamas Szoradi, Nora L. Herzog, Shivanjali Saxena, Farida Ettefa, Sarah Keegan, Gregory P. Brittingham, Gururaj R Kidiyoor, David Fenyö, Tong Shu, Morgan Delarue, Liam J. Holt, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of California [San Francisco] (UC San Francisco), University of California (UC), Équipe Micro-Nanofluidique pour les sciences de la vie et de l’environnement (LAAS-MILE), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), and Université de Toulouse (UT)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Nucleoplasm, biology, Heterochromatin, Nucleolus, Chemistry, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Nanoparticle, [SDV.CAN]Life Sciences [q-bio]/Cancer, RNA polymerase II, Mitotic chromosome condensation, Cytosol, medicine.anatomical_structure, medicine, biology.protein, Biophysics, Nucleus
Abstract

The cell interior is highly crowded and far from thermodynamic equilibrium. This environment can dramatically impact molecular motion and assembly, and therefore influence subcellular organization and biochemical reaction rates. These effects depend strongly on length-scale, with the least information available at the important mesoscale (10-100 nanometers), which corresponds to the size of crucial regulatory molecules such as RNA polymerase II. It has been challenging to study the mesoscale physical properties of the nucleoplasm because previous methods were labor-intensive and perturbative. Here, we report nuclear Genetically Encoded Multimeric nanoparticles (nucGEMs). Introduction of a single gene leads to continuous production and assembly of protein-based bright fluorescent nanoparticles of 40 nm diameter. We implemented nucGEMs in budding and fission yeast and in mammalian cell lines. We found differences in particle motility between the nucleus and the cytosol at the mesoscale, that mitotic chromosome condensation ejects nucGEMs from the nucleus, and that nucGEMs are excluded from heterochromatin and the nucleolus. nucGEMs enable hundreds of nuclear rheology experiments per hour, and allow evolutionary comparison of the physical properties of the cytosol and nucleoplasm.

Published
2021

23. Stress among Emergency Health Care Workers on Nuclear or Radiation Disaster: A Preliminary State Survey

Author

Carole Pelissier, Bruno Pereira, Vincent Roux, Frédéric Dutheil, Jean-Baptiste Bouillon-Minois, Valentin Navel, Mara Flannery, Céline Occelli, Jeannot Schmidt, CHU Clermont-Ferrand, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Universitaire de Nice (CHU Nice), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and LAPSCO, HAL

Subjects
medicine.medical_specialty, Health, Toxicology and Mutagenesis, Health Personnel, [SHS.PSY]Humanities and Social Sciences/Psychology, Disaster Planning, Computer-assisted web interviewing, Article, [SHS.PSY] Humanities and Social Sciences/Psychology, Disasters, 03 medical and health sciences, stress, 0302 clinical medicine, prevention, emergency medicine, Surveys and Questionnaires, Health care, medicine, Humans, 030212 general & internal medicine, Stress assessment, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Public health, public health, Public Health, Environmental and Occupational Health, 030208 emergency & critical care medicine, State survey, Nuclear power, medicine.disease, 3. Good health, radiation, nuclear, Work (electrical), disaster, Mandate, Medicine, Medical emergency, business, Emergency Service, Hospital, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: The nuclear or radiation disaster risk within the French Auvergne-Rhone-Alpes state is low (but not absent) due to its proximity to four Nuclear Power Generation Centers and two regional cancer control centers. This study aims to compare subjective stress ratings for emergency health care workers regarding nuclear and radiation disasters between two locations: at work versus at home. Materials and Methods: We distributed an anonymous online questionnaire via RedCap® to all emergency health care workers who could be involved in patient care after a nuclear or radiation disaster. It comprised 18 questions divided into three parts—theoretical knowledge and practical assessment, stress assessment, and sociodemographic criteria. Results: We analyzed 107 responses. There was a significant 11-point increase in stress levels between work and home regarding nuclear or radiation disaster risks (p = 0.01). Less than 25% of emergency health care workers surveyed benefited from annual training. Conclusion: The stress levels of emergency health care workers regarding nuclear or radiation disaster were higher at work than at home and increased without annual training. It is important to increase knowledge about these protocols and to mandate yearly training for all workers potentially involved in these disasters.

Published
2021

24. Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients

Author

Chloe Verducci, Eleonora Aronica, Roland D. Thijs, Evgeny Kanshin, Beate Diehl, Eleanor Drummond, Bei Jun Chen, Johannes C. Baayen, Thomas Wisniewski, Catherine Scott, Sander Idema, Dominique Leitner, Erwin A. van Vliet, Orrin Devinsky, Sasha Devore, Beatrix Ueberheide, Arline Faustin, Daniel Friedman, Geoffrey Pires, Michael Janitz, Jasper J. Anink, Manor Askenazi, Maria Thom, James D. Mills, Shruti Nayak, Pathology, APH - Aging & Later Life, APH - Mental Health, ANS - Cellular & Molecular Mechanisms, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Amsterdam [Amsterdam] (UvA), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), The University of Sydney, University of New South Wales [Sydney] (UNSW), Vrije Universiteit Amsterdam [Amsterdam] (VU), Swammerdam Institute for Life Sciences (SILS), University College of London [London] (UCL), Gestionnaire, Hal Sorbonne Université, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Cellular and Computational Neuroscience (SILS, FNWI)

Subjects
0301 basic medicine, Adult, Male, Proteomics, Brain activity and meditation, [SDV]Life Sciences [q-bio], Hippocampus, Electroencephalography, Bioinformatics, Article, Arousal, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Cortex (anatomy), medicine, Humans, Sudden Unexpected Death in Epilepsy, Child, Temporal cortex, Cerebral Cortex, medicine.diagnostic_test, business.industry, Gene Expression Profiling, Middle Aged, medicine.disease, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Epilepsy syndromes, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Signal Transduction
Abstract

ObjectiveTo identify the molecular signaling pathways underlying sudden unexpected death in epilepsy (SUDEP) and high-risk SUDEP compared to control patients with epilepsy.MethodsFor proteomics analyses, we evaluated the hippocampus and frontal cortex from microdissected postmortem brain tissue of 12 patients with SUDEP and 14 with non-SUDEP epilepsy. For transcriptomics analyses, we evaluated hippocampus and temporal cortex surgical brain tissue from patients with mesial temporal lobe epilepsy: 6 low-risk and 8 high-risk SUDEP as determined by a short (ResultsIn autopsy hippocampus and cortex, we observed no proteomic differences between patients with SUDEP and those with non-SUDEP epilepsy, contrasting with our previously reported robust differences between epilepsy and controls without epilepsy. Transcriptomics in hippocampus and cortex from patients with surgical epilepsy segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 long noncoding RNAs, 3 pending) in hippocampus.ConclusionThe SUDEP proteome and high-risk SUDEP transcriptome were similar to those in other patients with epilepsy in hippocampus and cortex, consistent with diverse epilepsy syndromes and comorbid conditions associated with SUDEP. Studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions, may identify molecular mechanisms of SUDEP.

Published
2021

25. HIST1H1E heterozygous protein‐truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals

Author

John M. Graham, Anna Ardissone, Dieter Kotzot, Paul R. Mark, Anna Zachariou, Guillermo Lay-Son, Allyn McConkie-Rosell, John Pappas, Karen Low, Fiona Stewart, Chey Loveday, Brian G. Skotko, Melissa Lees, Helen Stewart, Ho Ming Luk, Cheryl Cytrynbaum, Rachel Horton, Siddharth Banka, Gerard Marion, Deborah J. Shears, Marie T. McDonald, Ricardo A. Verdugo, Christine Coubes, Yuri A. Zarate, Christophe Phillipe, Katrina Tatton-Brown, Clare Allen, Deepika D.Cunha Burkardt, Rosanna Weksberg, I. Karen Temple, Alexia Bourgois, David J. Amor, Frédéric Tran Mau-Them, Laurence Faivre, Case Western Reserve University [Cleveland], The institute of cancer research [London], University College London Hospitals (UCLH), Murdoch Children's Research Institute (MCRI), University of Melbourne, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Manchester [Manchester], Manchester University NHS Foundation Trust (MFT), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), The Hospital for sick children [Toronto] (SickKids), Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), University Hospital Southampton NHS Foundation Trust, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Pontificia Universidad Católica de Chile (UC), Great Ormond Street Hospital for Children [London] (GOSH), University Hospitals Bristol, Department of Health Clinical Genetic Service Centre, Spectrum Health [Grand Rapids], Department of Molecular Genetics and Microbiology [Durham] (MGM), Duke University [Durham], New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Harvard Medical School [Boston] (HMS), Belfast City Hospital, Oxford University Hospitals NHS Trust, University of Oxford [Oxford], University of Southampton, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Universitad de Chile, Arkansas Children's Hospital, Cedars-Sinai Medical Center, St George’s University Hospitals, and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Heterozygote, Bioinformatics, Corpus callosum, Rahman syndrome, Histones, 03 medical and health sciences, Frontal Bossing, 0302 clinical medicine, HIST1H1E, Gene cluster, Intellectual disability, Genetics, Humans, Learning, Medicine, Epigenetics, Genetics (clinical), 030304 developmental biology, Behavior, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, epigenetic regulator gene, biology, business.industry, Facies, Heterozygote advantage, Syndrome, medicine.disease, Phenotype, Histone, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, intellectual disability, Mutation, biology.protein, Growth and Development, business, 030217 neurology & neurosurgery
Abstract

International audience; Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, OMIM #617537) is a recently described intellectual disability (ID) syndrome. Since the initial description of five unrelated individuals with three different heterozygous protein-truncating variants (PTVs) in the HIST1H1E gene in 2017, we have recruited 30 patients, all with HIST1H1E PTVs that result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain. The identification of 30 patients with HIST1H1E variants has allowed the clarification of the HIST1H1E syndrome phenotype. Major findings include an ID and a recognizable facial appearance. ID was reported in all patients and is most frequently of moderate severity. The facial gestalt consists of a high frontal hairline and full lower cheeks in early childhood and, in later childhood and adulthood, affected individuals have a strikingly high frontal hairline, frontal bossing, and deep-set eyes. Other associated clinical features include hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, skeletal anomalies, and cardiac anomalies. Brain magnetic resonance imaging (MRI) is frequently abnormal with a slender corpus callosum a frequent finding.

Published
2019

26. Algorithmic Learning for Auto-deconvolution of GC-MS Data to Enable Molecular Networking within GNPS

Author

Kelem Gashu, Madeleine Ernst, Mélissa Nothias Esposito, Kirill Veselkov, Michael M. Meijler, Robert A. Quinn, Gaud Dervilly, Audrey Poirier, Katherine N. Maloney, tzhak MizrahiI, Chao Song, Thomas O. Metz, Roman S. Borisov, Rob Knight, Mabel Gonzalez, Roxana Coras, Amina Bouslimani, Chiara Carazzone, Vasilis Vasiliou, Alexander A. Aksenov, Wout Bittremieux, Yann Guitton, Daniel Petras, Zheng Zhang, Larisa N. Kulikova, Robin Schmid, Ilaria Belluomo, James T. Morton, Sneha P. Couvillion, Brooke Anderson, Carrie D. Nicora, Kenneth L. Jones, S. Prévost, Sophie L. F. Doran, Louis-Félix Nothias, Dennis Veselkov, Erika M. Zink, Bruno Le Bizec, Andrea M. Smania, Chris Callewaert, Justin J. J. van der Hooft, Rachel Gregor, Pauline Le Boulch, Alexey V. Melnik, Adolfo Amézquita, Biswapriya B. Misra, Noga Sikron Persi, Mingxun Wang, Raphaël Lugan, Rachel Dutton, Morgan Panitchpakdi, Pieter C. Dorrestein, Meagan C. Burnet, Elizabeth Humston Fulmer, Ivan Laponogov, George B. Hanna, Viatcheslav B. Artaev, Kathleen Dorrestein, Aaron Fait, Andrea Georgina Albarracín Orio, Stav Eyal, Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Collaborative Mass Spectrometry Innovation Center, Imperial College London, University of California, Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Statens Serum Institut [Copenhagen], Wageningen University and Research [Wageningen] (WUR), Universidad de los Andes [Bogota] (UNIANDES), Center for Microbial Ecology and Technology (CMET), Universiteit Gent = Ghent University [Belgium] (UGENT), Michigan State University [East Lansing], Michigan State University System, Universidad Católica de Córdoba, Universidad Nacional de Córdoba [Argentina], Pacific Northwest National Laboratory (PNNL), LECO Corporation, Ben-Gurion University of the Negev (BGU), University of San Diego, Démarche intégrée pour l'obtention d'aliments de qualité (UMR QualiSud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), West Coast Metabolomics Center, University of California [Davis] (UC Davis), Max Planck Institute for Molecular Plant Physiology, Center of Plant Systems Biology and Biotechnology [Plovdiv] (CPSBB), NHS Foundation Trust [London], The Royal Marsden, Yale School of Public Health (YSPH), Institute of Inorganic Chemistry and Analytical Chemistry, A.V. Topchiev Institute of Petrochemical Synthesis (TIPS), Russian Academy of Sciences [Moscow] (RAS), and Peoples Friendship University of Russia [RUDN University] (RUDN)

Subjects
0303 health sciences, 03 medical and health sciences, Computer science, [SDV]Life Sciences [q-bio], 010401 analytical chemistry, Molecular networking, Deconvolution, Gas chromatography–mass spectrometry, 01 natural sciences, Data science, 030304 developmental biology, 0104 chemical sciences
Abstract

Gas chromatography-mass spectrometry (GC-MS) represents an analytical technique with significant practical societal impact. Spectral deconvolution is an essential step for interpreting GC-MS data. No public GC-MS repositories that also enable repository-scale analysis exist, in part because deconvolution requires significant user input. We therefore engineered a scalable machine learning workflow for the Global Natural Product Social Molecular Networking (GNPS) analysis platform to enable the mass spectrometry community to store, process, share, annotate, compare, and perform molecular networking of GC-MS data. The workflow performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization, using a Fast Fourier Transform-based strategy to overcome scalability limitations. We introduce a “balance score” that quantifies the reproducibility of fragmentation patterns across all samples. We demonstrate the utility of the platform with breathomics analysis applied to the early detection of oesophago-gastric cancer, and by creating the first molecular spatial map of the human volatilome.

Published
2021

27. Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway

Author

Jean-Laurent Casanova, Isabelle Meyts, Department of Microbiology, Immunology and Transplantation [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), Paris Diderot, Equipe HAL, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, and NYU System (NYU)-NYU System (NYU)

Subjects
Protective immunity, Genotype, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Receptor, Interferon alpha-beta, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Immunity, medicine, Animals, Humans, Immunology and Allergy, Genetic Predisposition to Disease, STAT1, STAT2, Alleles, 030304 developmental biology, Mice, Knockout, TYK2 Kinase, 0303 health sciences, biology, Ifn response, STAT2 Transcription Factor, Janus Kinase 1, Interferon-Stimulated Gene Factor 3, gamma Subunit, 3. Good health, [SDV] Life Sciences [q-bio], Disease Models, Animal, Phenotype, STAT1 Transcription Factor, Cytokine, Virus Diseases, Tyrosine kinase 2, Interferon Type I, Mutation, biology.protein, Interferons, Signal transduction, Job Syndrome, Signal Transduction, 030215 immunology
Abstract

Type I interferons (IFNs) are so-named because they interfere with viral infection in vertebrate cells. The study of cellular responses to type I IFNs led to the discovery of the JAK-STAT signaling pathway, which also governs the response to other cytokine families. We review here the outcome of viral infections in mice and humans with engineered and inborn deficiencies, respectively, of (i) IFNAR1 or IFNAR2, selectively disrupting responses to type I IFNs, (ii) STAT1, STAT2, and IRF9, also impairing cellular responses to type II (for STAT1) and/or III (for STAT1, STAT2, IRF9) IFNs, and (iii) JAK1 and TYK2, also impairing cellular responses to cytokines other than IFNs. A picture is emerging of greater redundancy of human type I IFNs for protective immunity to viruses in natural conditions than was initially anticipated. Mouse type I IFNs are essential for protection against a broad range of viruses in experimental conditions. These findings suggest that various type I IFN-independent mechanisms of human cell-intrinsic immunity to viruses have yet to be discovered. This article is protected by copyright. All rights reserved.

Published
2021

28. Human ancient DNA analyses reveal the high burden of tuberculosis in Europeans over the last 2,000 years

Author

Kerner, Gaspard, Laval, Guillaume, Patin, Etienne, Boisson-Dupuis, Stéphanie, Abel, Laurent, Casanova, Jean-Laurent, Quintana-Murci, Lluis, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Human genetics of infectious diseases: Complex predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Rockefeller University [New York], Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Fondation pour la Recherche Médicale (EQU201903007798), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-17-CE12-0018,LifeChange,Déchiffrer les conséquences biologiques et pathogéniques liées à un changement majeur de mode de vie(2017), ANR-19-CE15-0009,CNSVIRGEN,Déficits immunitaires innés dans les infections sévères du tronc cérébral(2019), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Collège de France - Chaire Génomique humaine et évolution, Quintana-Murci, lluis, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Déchiffrer les conséquences biologiques et pathogéniques liées à un changement majeur de mode de vie - - LifeChange2017 - ANR-17-CE12-0018 - AAPG2017 - VALID, and Déficits immunitaires innés dans les infections sévères du tronc cérébral - - CNSVIRGEN2019 - ANR-19-CE15-0009 - AAPG2019 - VALID

Subjects
Male, TYK2 Kinase, disease, Polymorphism, Genetic, Europeans, Genome, Human, natural selection, Mycobacterium tuberculosis, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Body Remains, Europe, tuberculosis, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Report, evolution, Approximate Bayesian Computation, Humans, Female, genetics, human, DNA, Ancient, ancient DNA, History, Ancient
Abstract

International audience; Tuberculosis (TB), usually caused by Mycobacterium tuberculosis bacteria, is the first cause of death from an infectious disease at the worldwide scale, yet the mode and tempo of TB pressure on humans remain unknown. The recent discovery that homozygotes for the P1104A polymorphism of TYK2 are at higher risk to develop clinical forms of TB provided the first evidence of a common, monogenic predisposition to TB, offering a unique opportunity to inform on human co-evolution with a deadly pathogen. Here, we investigate the history of human exposure to TB by determining the evolutionary trajectory of the TYK2 P1104A variant in Europe, where TB is considered to be the deadliest documented infectious disease. Leveraging a large dataset of 1,013 ancient human genomes and using an approximate Bayesian computation approach, we find that the P1104A variant originated in the common ancestors of West Eurasians $30,000 years ago. Furthermore, we show that, following large-scale population movements of Anatolian Neolithic farmers and Eurasian steppe herders into Europe, P1104A has markedly fluctuated in frequency over the last 10,000 years of European history, with a dramatic decrease in frequency after the Bronze Age. Our analyses indicate that such a frequency drop is attributable to strong negative selection starting $2,000 years ago, with a relative fitness reduction on homozygotes of 20%, among the highest in the human genome. Together, our results provide genetic evidence that TB has imposed a heavy burden on European health over the last two millennia.

Published
2021

29. Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method

Author

Ognjen Gajic, Samuel M. Galvagno, Elie Azoulay, Adam M. Deane, Jan Bakker, Massimo Antonelli, Sangeeta Mehta, Pauline K. Park, Yaseen M. Arabi, David Pilcher, Krishnaswamy Sundararajan, Gopi C. Khilnani, Paolo Pelosi, Suveer Singh, Laurent Brochard, Younsuck Koh, Bin Du, Massimiliano Sorbello, Waleed Alhazzani, Jason Phua, Lise Piquilloud, John Victor Peter, Prashant Nasa, Sachin Gupta, Armand Mekontso-Dessap, Manu L N G Malbrain, Sharon Einav, Michael T. McCurdy, Manu Shankar-Hari, Claude Guérin, Yash Javeri, Jean-Baptiste Lascarrou, Samir Jaber, Ashish Khanna, Jordi Mancebo, Pradeep Rangappa, Deven Juneja, Andrés Esteban, Sheila Nainan Myatra, Marcus J. Schultz, Ravindranath Tiruvoipati, Andrew A. Udy, Brendan McGrath, Flávia Ribeiro Machado, Michael Nurok, Tobias Welte, Mervyn Mer, Ravi Jain, Peter Schellongowski, NMC Specialty Hospital, Al Nahda, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Mahatma Gandhi Hospital, Narayana Super Speciality Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, King Saud Bin Abdulaziz University for Health Sciences [Riyadh] (KSAU-HS), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Pontificia Universidad Católica de Chile (UC), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], The Royal Melbourne Hospital, Peking Union Medical College Hospital [Beijing] (PUMCH), Shaare Zedek Medical Center [Jerusalem, Israel], CIBER de Epidemiología y Salud Pública (CIBERESP), Mayo Clinic, University of Maryland School of Medicine, University of Maryland System, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Ulsan, Centre hospitalier universitaire de Nantes (CHU Nantes), Federal University of Sao Paulo (Unifesp), International Fluid Academy, Vrije Universiteit Brussel [Bruxelles] (VUB), Hospital Universitari Sant Pau, Barcelona, Manchester University NHS Foundation Trust (MFT), Manchester Academic Health Sciences Centre [Manchester, UK], Mount Sinai Health System, Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, University of the Witwatersrand [Johannesburg] (WITS), Cedars-Sinai Medical Center, University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Ospedale Policlinico San Martino [Genoa], Università degli studi di Genova = University of Genoa (UniGe), Christian Medical College and Hospital Ludhiana [Punjab, India] (CMCHL), National and Kapodistrian University of Athens (NKUA), Monash University [Melbourne], Lausanne University Hospital, Medizinische Universität Wien = Medical University of Vienna, VU University Medical Center [Amsterdam], Mahidol University [Bangkok], University of Oxford [Oxford], Guy's and St Thomas' Hospital [London], King‘s College London, Royal Brompton Hospital, Chelsea and Westminster Hospital, Monash College [Melbourne], German Center for Lung Research - DZL [Munich, Germany], Tata Memorial Centre, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, AII - Infectious diseases, ACS - Diabetes & metabolism, ACS - Microcirculation, and Epidemiology

Subjects
medicine.medical_specialty, ARDS, COVID-19 acute respiratory distress syndrome, Consensus, Delphi Technique, medicine.medical_treatment, education, Delphi method, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Prone ventilation, 03 medical and health sciences, 0302 clinical medicine, Respiratory Insufficiency/therapy, COVID-19 high flow nasal oxygen, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, COVID-19 respiratory management, medicine, Humans, COVID-19/complications, Respiratory Insufficiency/virology, COVID 19 invasive mechanical ventilation, COVID-19 ventilatory management, Respiratory distress syndrome adult, Intensive care medicine, Personal protective equipment, Positive end-expiratory pressure, 11 Medical and Health Sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Research, Tracheal intubation, lcsh:Medical emergencies. Critical care. Intensive care. First aid, COVID-19, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, Emergency & Critical Care Medicine, COVID-19 high fow nasal oxygen, 3. Good health, 030228 respiratory system, Respiratory failure, Breathing, business, Respiratory Insufficiency
Abstract

Background Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Methods Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p Results Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Conclusion Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Published
2021

30. Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance

Author

Lluis Quintana-Murci, Etienne Patin, Jean-Laurent Casanova, Laurent Abel, Anne Puel, Jérémie Rosain, Shen-Ying Zhang, Vivien Béziat, Joseph G. Gleeson, Anne Gregor, Emmanuelle Jouanguy, Franck Rapaport, Stéphanie Boisson-Dupuis, Qian Zhang, Bertrand Boisson, Jacinta Bustamante, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Center for the Study of Primary Immunodeficiencies [Paris], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute [La Jolla, CA, USA], Rady Children’s Institute of Genomic Medicine [La Jolla, CA, USA], University of California, Laboratory for Pediatric Brain Disease, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF (institution)), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU), This work was supported in part by the Rockefeller University, the St. Giles Foundation, Institut National de la Santé et de la Recherche Médicale, Paris Descartes University, the National Center for Research Resources and the National Center for Advancing Sciences, NIH Clinical and Translational Science Award program (Grant UL1TR001866), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID), and the French National Research Agency (ANR) (Grants ANR-10-IAHU-01, ANR-15-CE17-0014). The laboratory of L.Q.-M. and E.P. is supported by the Institut Pasteur, the Collège de France, the Investissement d’Avenir program, Laboratoires d’Excellence 'Milieu Intérieur' (Grant ANR-10-LABX-69-01), Fondation pour la Recherche Médicale (Grant FRM DEQ20180339214), Fondation Allianz–Institut de France, and Fondation de France., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-15-CE17-0014,ProgLegio,Biomarqueurs bactériens et humains d'intérêt pronostic pour les légionelloses sévères(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of California (UC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège de France - Chaire Génomique humaine et évolution, Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Candidate gene, Population, Genes, Recessive, Biology, 03 medical and health sciences, Negative selection, 0302 clinical medicine, Humans, Selection, Genetic, education, Selection (genetic algorithm), Loss function, Genes, Dominant, 030304 developmental biology, Genetics, 0303 health sciences, education.field_of_study, Multidisciplinary, Mechanism (biology), Immunity, Inheritance (genetic algorithm), Genetic Variation, Biological Sciences, Penetrance, 3. Good health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Metabolism, Inborn Errors, 030217 neurology & neurosurgery
Abstract

International audience; Genetic variants underlying life-threatening diseases, being unlikely to be transmitted to the next generation, are gradually and selectively eliminated from the population through negative selection. We study the determinants of this evolutionary process in human genes underlying monogenic diseases by comparing various negative selection scores and an integrative approach, CoNeS, at 366 loci underlying inborn errors of immunity (IEI). We find that genes underlying autosomal dominant (AD) or X-linked IEI have stronger negative selection scores than those underlying autosomal recessive (AR) IEI, whose scores are not different from those of genes not known to be disease causing. Nevertheless, genes underlying AR IEI that are lethal before reproductive maturity with complete penetrance have stronger negative selection scores than other genes underlying AR IEI. We also show that genes underlying AD IEI by loss of function have stronger negative selection scores than genes underlying AD IEI by gain of function, while genes underlying AD IEI by haploinsufficiency are under stronger negative selection than other genes underlying AD IEI. These results are replicated in 1,140 genes underlying inborn errors of neurodevelopment. Finally, we propose a supervised classifier, SCoNeS, which predicts better than state-of-the-art approaches whether a gene is more likely to underlie an AD or AR disease. The clinical outcomes of monogenic inborn errors, together with their mode and mechanisms of inheritance, determine the levels of negative selection at their corresponding loci. Integrating scores of negative selection may facilitate the prioritization of candidate genes and variants in patients suspected to carry an inborn error.

Published
2021

31. Results of the 2020 fastMRI Challenge for Machine Learning MR Image Reconstruction

Author

Yohan Jun, Simon Arberet, Jean-Luc Starck, Dominik Nickel, Alireza Radmanesh, Yvonne W. Lui, Sunwoo Kim, Matthew J. Muckley, Mahmoud Mostapha, Jonas Teuwen, Zhengnan Huang, Nafissa Yakubova, Dosik Hwang, Geunu Jeong, Zaccharie Ramzi, Florian Knoll, Anuroop Sriram, Philippe Ciuciu, Chaoping Zhang, Bruno Riemenschneider, Hyungseob Shin, Jingyu Ko, Dimitrios Karkalousos, Facebook AI Research [New York] (FAIR), Facebook, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), AIRS Medical [Seoul], Yonsei University, Siemens Healthineers, Digital Services, Digital Technology and Innovation, Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service NEUROSPIN (NEUROSPIN), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Radboud University Medical Center [Nijmegen], Amsterdam UMC, Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Amsterdam UMC - Amsterdam University Medical Center

Subjects
FOS: Computer and information sciences, fast imaging, medicine.medical_specialty, Computer science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Computer Vision and Pattern Recognition (cs.CV), Computer Science - Computer Vision and Pattern Recognition, Neuroimaging, 02 engineering and technology, Iterative reconstruction, Article, Data modeling, Machine Learning, 03 medical and health sciences, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Research community, 0202 electrical engineering, electronic engineering, information engineering, medicine, FOS: Electrical engineering, electronic engineering, information engineering, Image Processing, Computer-Assisted, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Medical physics, Challenge, Electrical and Electronic Engineering, MR image reconstruction, parallel imaging, 030304 developmental biology, compressed sensing, 0303 health sciences, Training set, Radiological and Ultrasound Technology, Principal (computer security), Image and Video Processing (eess.IV), Brain, 020206 networking & telecommunications, public data set, Electrical Engineering and Systems Science - Image and Video Processing, 16. Peace & justice, Magnetic Resonance Imaging, Computer Science Applications, 13. Climate action, Mr images, optimization, Software
Abstract

Accelerating MRI scans is one of the principal outstanding problems in the MRI research community. Towards this goal, we hosted the second fastMRI competition targeted towards reconstructing MR images with subsampled k-space data. We provided participants with data from 7,299 clinical brain scans (de-identified via a HIPAA-compliant procedure by NYU Langone Health), holding back the fully-sampled data from 894 of these scans for challenge evaluation purposes. In contrast to the 2019 challenge, we focused our radiologist evaluations on pathological assessment in brain images. We also debuted a new Transfer track that required participants to submit models evaluated on MRI scanners from outside the training set. We received 19 submissions from eight different groups. Results showed one team scoring best in both SSIM scores and qualitative radiologist evaluations. We also performed analysis on alternative metrics to mitigate the effects of background noise and collected feedback from the participants to inform future challenges. Lastly, we identify common failure modes across the submissions, highlighting areas of need for future research in the MRI reconstruction community., Comment: M. J. Muckley and B. Riemenschneider contributed equally to this work. This updates to version accepted in IEEE Transactions on Medical Imaging. It includes a rewrite of Section II.E as well as minor changes and corrections

Published
2021

32. Reactive astrocyte nomenclature, definitions, and future directions

Author

Arthur M. Butt, Elena Galea, Richard M. Ransohoff, Raymond A. Swanson, Eduardo R. Zimmer, Christopher M. Norris, Gilles Bonvento, Andras Lakatos, Philip G. Haydon, Wei Ting Chen, Christine R. Rose, Alexey Semyanov, Nicola J. Allen, Anna V. Molofsky, Javier Vitorica, Seiji Okada, Alfonso Araque, Antonia Gutierrez, Masamitsu Iino, Alberto Serrano-Pozo, Vittorio Gallo, C. Justin Lee, Magdalena Götz, Baljit S. Khakh, Christian Steinhäuser, Bart De Strooper, Stéphane H. R. Oliet, Andrea Volterra, Swetlana Sirko, Kira E. Poskanzer, Michael V. Sofroniew, Giorgio Carmignoto, Elly M. Hol, Frank W. Pfrieger, Beatriz G. Pérez-Nievas, Ksenia V. Kastanenka, Keith K. Murai, James P. O'Callaghan, Ina B. Wanner, David H. Rowitch, Pierre J. Magistretti, Cinthia Farina, Marcela Pekna, Albee Messing, Jia Qian Wu, Shane A. Liddelow, Dieter Henrik Heiland, Anusha Mishra, Robert Zorec, Levi B. Wood, Marc R. Freeman, Matthew Holt, Luis Barbeito, Gabor C. Petzold, Luc Pellerin, Jeffrey D. Rothstein, Nathalie Rouach, Carole Escartin, Schuichi Koizumi, Gertrudis Perea, Dwight E. Bergles, Miriam Riquelme-Perez, Martine Cohen-Salmon, Stefanie Robel, James E. Goldman, Binhai Zheng, João Filipe Oliveira, Ari Barzilai, Steven A. Goldman, Brian A. MacVicar, Aude Panatier, Helmut Kettenmann, Alexei Verkhratsky, Amit Agarwal, Colm Cunningham, Blanca Diaz-Castro, Francisco J. Quintana, Milos Pekny, Harald Sontheimer, Benjamin Deneen, Vladimir Parpura, Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Universitat Autònoma de Barcelona (UAB), ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), Universitat Pompeu Fabra [Barcelona] (UPF), University of Cambridge [UK] (CAM), National Institute for Occupational Safety and Health [Morgantown, WV, USA] (NIOSH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University Hospital Bonn, Massachusetts General Hospital [Charlestown, MA, États-Unis], University of Bonn, University of Lausanne (UNIL), Italian National Research Council [Padova, Italy], University of Padua [Italy], Heidelberg University, The Salk Institute for Biological Studies, University of Minnesota [MN, USA], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Tel Aviv University [Tel Aviv], Johns Hopkins University School of Medicine [Baltimore], University of Portsmouth, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Trinity College Dublin, Baylor College of Medicine (BCM), Baylor University, University College of London [London] (UCL), University of Edinburgh, San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Vollum Institute, Vollum Institute OHSU, National Children's Hospital, Columbia University [New York], University of Rochester Medical Center (URMC), University of Copenhagen = Københavns Universitet (KU), Ludwig Maximilians Universitaet, SYNERGY, Excellence Cluster of Systems Neurology, Ludwig-Maximilians-Universität München (LMU), Universidad de Málaga [Málaga] = University of Málaga [Málaga], Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Tufts University School of Medicine [Boston], University of Freiburg [Freiburg], Utrecht University [Utrecht], VIB-KU Leuven Center for Brain & Disease Research [Leuven, Belgium], Nihon University School of Medicine [Tokyo, Japan], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Yamanashi University, Institute for Basic Science [Daejeon] (IBS), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of British Columbia (UBC), King Abdullah University of Science and Technology, University of Wisconsin-Madison, Oregon Health and Science University [Portland] (OHSU), University of California [San Francisco] (UCSF), University of California, McGill University Health Center [Montreal] (MUHC), University of Kentucky, Kyushu University [Fukuoka], Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minho [Braga], ICVS/3B's—PT Government Associate Laboratory [Braga, Portugal], Polytechnic Institute of Cávado and Ave, University of Alabama at Birmingham [ Birmingham] (UAB), University of Gothenburg (GU), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Cajal Institute, King‘s College London, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Third Rock Ventures, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (IBCh RAS), Russian Academy of Sciences [Moscow] (RAS), Sechenov First Moscow State Medical University, Ludwig Maximilian University [Munich] (LMU), Institute for Stem Cell Research [Neuherberg], Helmholtz-Zentrum München (HZM), Universidad de Sevilla, Georgia Institute of Technology [Atlanta], The University of Texas Health Science Center at Houston (UTHealth), UC San Diego School of Medicine, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), University of Ljubljana, University of Manchester [Manchester], Ikerbasque - Basque Foundation for Science, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), European Project: 722053,EU-GliaPhD - H2020-EU.1.3. H2020-EU.1.3.1., Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Universität Bonn = University of Bonn, Université de Lausanne = University of Lausanne (UNIL), Escartin, Carole [0000-0003-3613-4118], Galea, Elena [0000-0003-4537-9897], Lakatos, András [0000-0002-1301-2292], Petzold, Gabor C [0000-0002-0145-8641], Serrano-Pozo, Alberto [0000-0003-0899-7530], Volterra, Andrea [0000-0003-1069-1602], Araque, Alfonso [0000-0003-3840-1144], Barbeito, Luis [0000-0002-3047-232X], Bonvento, Gilles [0000-0002-2886-4228], Butt, Arthur M [0000-0001-7579-0746], Deneen, Benjamin [0000-0002-6335-1081], Farina, Cinthia [0000-0002-4466-9676], Gallo, Vittorio [0000-0002-2429-0845], Goldman, Steven A [0000-0002-5498-4303], Götz, Magdalena [0000-0003-1551-9203], Gutiérrez, Antonia [0000-0002-6264-6152], Haydon, Philip G [0000-0001-5698-6698], Heiland, Dieter H [0000-0002-9258-3033], Hol, Elly M [0000-0001-5604-2603], Holt, Matthew G [0000-0002-8958-4027], Koizumi, Schuichi [0000-0001-6184-3106], MacVicar, Brian A [0000-0003-4596-4623], Mishra, Anusha [0000-0002-3642-5049], Molofsky, Anna V [0000-0002-4709-2411], Okada, Seiji [0000-0002-5107-8209], Oliveira, João F [0000-0002-1005-2328], Panatier, Aude [0000-0002-6107-4463], Pekna, Marcela [0000-0003-2734-8237], Perea, Gertrudis [0000-0001-5924-9175], Pfrieger, Frank W [0000-0001-7085-1431], Poskanzer, Kira E [0000-0003-4830-8891], Rose, Christine R [0000-0002-9684-3592], Rothstein, Jeffrey D [0000-0003-2001-8470], Rouach, Nathalie [0000-0002-5574-888X], Rowitch, David H [0000-0002-0079-0060], Semyanov, Alexey [0000-0002-6800-0942], Sirko, Swetlana [0000-0001-5950-616X], Sontheimer, Harald [0000-0002-5843-9871], Swanson, Raymond A [0000-0002-3664-5359], Zorec, Robert [0000-0002-7478-3875], Sofroniew, Michael V [0000-0001-6075-0178], Verkhratsky, Alexei [0000-0003-2592-9898], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Aging, [SDV]Life Sciences [q-bio], Disease, pathology [Spinal Cord], Article, 03 medical and health sciences, 0302 clinical medicine, pathology [Aging], Response to injury, pathology [Brain], medicine, Psychology, Animals, Humans, ddc:610, Reactive Astrocyte, ComputingMilieux_MISCELLANEOUS, Spinal Cord Injuries, pathology [Astrocytes], Brain Diseases, Neurology & Neurosurgery, Extramural, business.industry, General Neuroscience, pathology [Brain Injuries], Neurosciences, pathology [Brain Diseases], Brain, 3. Good health, Brain Disorders, 030104 developmental biology, medicine.anatomical_structure, Spinal Cord, Astrocytes, Brain Injuries, Neurological, Cognitive Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], pathology [Spinal Cord Injuries], business, Neuroscience, 030217 neurology & neurosurgery, Astrocyte, Spinal cord pathology
Abstract

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters—preferably in vivo—plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions., Funding: CNRS, CEA, ANR, and France Alzheimer to CE.; MCINN (PID2019-107633RB-I00) and Generalitat de Catalunya (2017-SGR547, Grup de demències Sant Pau) to E.G. US Centers for Disease Control and Prevention to J. P.O. Alzheimer’s Association (AACF-17-524184) and NIH-NIA (K08AG064039) to A.S.-P. DFG (SPP1757, STE 552/5, STE 552/4), EU (H2020-MSCA-ITN project 722053 EU-GliaPhD) and BMBF (16GW0182 CONNEXIN) to C.S. Swiss National Science Foundation grant 31003A 173124/1; SNSF NCCR ‘Transcure’ (51NF40-160620); Synapsis Foundation Heidi Seiler-Stiftung 2018-PI01 to A.Volterra. NIH-NINDS (NS084030), Dr. Miriam and Sheldon G. Adelson Medical Foundation and Wings for Life to M.V.S. The authors thank T. Yohannan of Alpha Language Services, Barcelona, for expert copy editing.

Published
2021

33. A call for a better understanding of the role of dietary amino acids and posttranslational protein modifications of microbiome in the progression of CKD

Author

Csaba P. Kovesdy, Shivam Joshi, Denise Mafra, Philippe Chauveau, Denis Fouque, Srinivasan Beddhu, Laetitia Koppe, Kamyar Kalantar-Zadeh, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), University of Utah School of Medicine [Salt Lake City], AURAD Aquitaine, Association Pour l'Utilisation Du Rein Artificiel A Domicile [Gradignan] (AURAD), The University of Tennessee Health Science Center [Memphis] (UTHSC), Fluminense Federal University [Niterói], New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of California [Irvine] (UCI), University of California, University of California [Irvine] (UC Irvine), University of California (UC), and CarMeN, laboratoire

Subjects
chemistry.chemical_classification, 0303 health sciences, Transplantation, business.industry, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Amino acid, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Low-protein diet, chemistry, Post translational, Biochemistry, Nephrology, medicine, Uremic toxins, Microbiome, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience; No abstract available

Published
2021

34. Proteomic differences in the hippocampus and cortex of epilepsy brain tissue

Author

Daniel Friedman, Manor Askenazi, Dominique Leitner, Arline Faustin, Eleanor Drummond, Evgeny Kanshin, Thomas Wisniewski, Shruti Nayak, Geoffrey Pires, Beatrix Ueberheide, Orrin Devinsky, Ludovic Debure, Gestionnaire, HAL Sorbonne Université 5, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, G protein, synaptophysin, Hippocampus, Neurological disorder, Biology, Hippocampal formation, Epileptogenesis, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, proteomics, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, seizures, 0303 health sciences, business.industry, Dentate gyrus, General Engineering, medicine.disease, 3. Good health, 030104 developmental biology, Frontal lobe, Synaptic plasticity, epilepsy, Original Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Neuroscience, GNB1, 030217 neurology & neurosurgery
Abstract

Epilepsy is a common neurological disorder affecting over 70 million people worldwide, with a high rate of pharmaco-resistance, diverse comorbidities including progressive cognitive and behavioural disorders, and increased mortality from direct (e.g. sudden unexpected death in epilepsy, accidents, drowning) or indirect effects of seizures and therapies. Extensive research with animal models and human studies provides limited insights into the mechanisms underlying seizures and epileptogenesis, and these have not translated into significant reductions in pharmaco-resistance, morbidities or mortality. To help define changes in molecular signalling networks associated with seizures in epilepsy with a broad range of aetiologies, we examined the proteome of brain samples from epilepsy and control cases. Label-free quantitative mass spectrometry was performed on the hippocampal cornu ammonis 1–3 region (CA1–3), frontal cortex and dentate gyrus microdissected from epilepsy and control cases (n = 14/group). Epilepsy cases had significant differences in the expression of 777 proteins in the hippocampal CA1 − 3 region, 296 proteins in the frontal cortex and 49 proteins in the dentate gyrus in comparison to control cases. Network analysis showed that proteins involved in protein synthesis, mitochondrial function, G-protein signalling and synaptic plasticity were particularly altered in epilepsy. While protein differences were most pronounced in the hippocampus, similar changes were observed in other brain regions indicating broad proteomic abnormalities in epilepsy. Among the most significantly altered proteins, G-protein subunit beta 1 (GNB1) was one of the most significantly decreased proteins in epilepsy in all regions studied, highlighting the importance of G-protein subunit signalling and G-protein-coupled receptors in epilepsy. Our results provide insights into common molecular mechanisms underlying epilepsy across various aetiologies, which may allow for novel targeted therapeutic strategies.

Published
2021

35. Transcranial magnetic stimulation entrains alpha oscillatory activity in occipital cortex

Author

Marisa Carrasco, Yong-Jun Lin, Antoni Valero-Cabré, Laura Dugué, Lavanya Shukla, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Université Paris sciences et lettres (PSL), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universitat Oberta de Catalunya [Barcelona] (UOC), Universitat Oberta de Catalunya (UOC), HAL-SU, Gestionnaire, New York University [New York] (NYU), NYU System (NYU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Open University of Catalonia [Barcelona], and VALERO CABRE, ANTONI

Subjects
Male, medicine.medical_treatment, Striate cortex, Stimulation, Electroencephalography, perception, neuroscience, cognitive neuroscience, 0302 clinical medicine, Cortex (anatomy), Physics, 0303 health sciences, striate cortex, Multidisciplinary, medicine.diagnostic_test, Pulse (signal processing), Middle Aged, Transcranial Magnetic Stimulation, Alpha Rhythm, medicine.anatomical_structure, Cortical Excitability, Visual Perception, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Occipital Lobe, Entrainment (chronobiology), Adult, Science, Alpha (ethology), Article, 03 medical and health sciences, Young Adult, Rhythm, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Cognitive neuroscience, Transcranial magnetic stimulation, visual system, Perception, Visual system, Neuroscience, 030217 neurology & neurosurgery
Abstract

Parieto-occipital alpha rhythms (8–12 Hz) underlie cortical excitability and influence visual performance. Whether the synchrony of intrinsic alpha rhythms in the occipital cortex can be entrained by transcranial magnetic stimulation (TMS) is an open question. We applied 4-pulse, 10-Hz rhythmic TMS to entrain intrinsic alpha oscillators targeting right V1/V2, and tested four predictions with concurrent electroencephalogram (EEG): (1) progressive enhancement of entrainment across time windows, (2) output frequency specificity, (3) dependence on the intrinsic oscillation phase, and (4) input frequency specificity to individual alpha frequency (IAF) in the neural signatures. Two control conditions with an equal number of pulses and duration were arrhythmic-active and rhythmic-sham stimulation. The results confirmed the first three predictions. Rhythmic TMS bursts significantly entrained local neural activity. Near the stimulation site, evoked oscillation amplitude and inter-trial phase coherence (ITPC) were increased for 2 and 3 cycles, respectively, after the last TMS pulse. Critically, ITPC following entrainment positively correlated with IAF rather than with the degree of similarity between IAF and the input frequency (10 Hz). Thus, we entrained alpha-band activity in occipital cortex for ~ 3 cycles (~ 300 ms), and IAF predicts the strength of entrained occipital alpha phase synchrony indexed by ITPC.

Published
2021

36. Ambulatory Blood Pressure Monitoring to Predict Response to Renal Denervation: A Post Hoc Analysis of the RADIANCE-HTN SOLO Study

Author

Sripal Bangalore, Yale Wang, Lisa Claude, Antoine Cremer, Melvin D. Lobo, Johannes Stegbauer, Joost Daemen, Ajay J. Kirtane, Michel Azizi, Yuyin Liu, Michael A. Weber, Philippe Gosse, Josephine Abraham, Kazuomi Kario, Manish Saxena, Cardiology, Hôpital Saint-André, Columbia University Medical Center (CUMC), Columbia University [New York], Queen Mary University of London (QMUL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Minneapolis Heart Institute, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System-Abbott Northwestern Hospital, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], State University of New York (SUNY), University of Utah, School of Medicine [Jichi Medical University, Japan], Jichi Medical University [Tochigi-Ken, Japan], New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Baim Institute for Clinical Research Boston MA, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
Adult, Male, medicine.medical_specialty, Ambulatory blood pressure, [SDV]Life Sciences [q-bio], Blood Pressure, 030204 cardiovascular system & hematology, Kidney, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Internal medicine, Heart rate, Post-hoc analysis, Internal Medicine, Medicine, Humans, In patient, 030212 general & internal medicine, Sympathectomy, renal denervation, Aged, Denervation, business.industry, Blood Pressure Monitoring, Ambulatory, Middle Aged, ambulatory blood pressure monitoring, Blood pressure, Treatment Outcome, Hypertension, Cardiology, Female, blood pressure variability, business
Abstract

Renal denervation (RDN) is effective in lowering blood pressure (BP) in patients with hypertension. The issue remains how to best identify potential responders. Ambulatory BP monitoring may be useful. Baseline nighttime systolic BP (SBP) ≥136 mm Hg and its variability (SD) ≥12 mm Hg in DENER-HTN trial or 24-hour heart rate ≥73.5 bpm in SPYRAL HTN-OFF MED Trial were shown to predict the BP response to RDN. We applied these criteria to the patients with hypertension in the sham-controlled RADIANCE-HTN SOLO trial to predict the BP response to ultrasound RDN at 2 months while patients were maintained off medications. BP responders were defined as: clinical with 24-hour SBP 90% irrespective of definition) but low sensitivity (from 9.1% to 30% depending on the definition) to predict responders; the heart rate criterion had insufficient predictive value. This analysis suggests the potential role of nighttime SBP and its variability to predict BP response to RDN in patients with hypertension. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02649426.

Published
2020

37. State-of-the-art Machine Learning MRI Reconstruction in 2020: Results of the Second fastMRI Challenge

Author

Muckley, Matthew, Riemenschneider, Bruno, Radmanesh, Alireza, Kim, Sunwoo, Jeong, Geunu, Ko, Jingyu, Jun, Yohan, Shin, Hyungseob, Hwang, Dosik, Mostapha, Mahmoud, Arberet, Simon, Nickel, Dominik, Ramzi, Zaccharie, Ciuciu, Philippe, Starck, Jean-Luc, Teuwen, Jonas, Karkalousos, Dimitrios, Zhang, Chaoping, Sriram, Anuroop, Huang, Zhengnan, Yakubova, Nafissa, Lui, Yvonne, Knoll, Florian, Facebook AI Research [New York] (FAIR), Facebook, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), AIRS Medical [Seoul], Yonsei University, Siemens Healthineers, Digital Services, Digital Technology and Innovation, Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service NEUROSPIN (NEUROSPIN), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Radboud University Medical Center [Nijmegen], and Amsterdam UMC

Subjects
[INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV]
Abstract

16 pages, 7 figures, 3 tables; Accelerating MRI scans is one of the principal outstanding problems in the MRI research community. Towards this goal, we hosted the second fastMRI competition targeted towards reconstructing MR images with subsampled k-space data. We provided participants with data from 7,299 clinical brain scans (de-identified via a HIPAA-compliant procedure by NYU Langone Health), holding back the fully-sampled data from 894 of these scans for challenge evaluation purposes. In contrast to the 2019 challenge, we focused our radiologist evaluations on pathological assessment in brain images. We also debuted a new Transfer track that required participants to submit models evaluated on MRI scanners from outside the training set. We received 19 submissions from eight different groups. Results showed one team scoring best in both SSIM scores and qualitative radiologist evaluations. We also performed analysis on alternative metrics to mitigate the effects of background noise and collected feedback from the participants to inform future challenges. Lastly, we identify common failure modes across the submissions, highlighting areas of need for future research in the MRI reconstruction community.

Published
2020

38. The Negative Impact of Night Shifts on Diet in Emergency Healthcare Workers

Author

Jean-Baptiste Bouillon-Minois, David Thivel, Carolyne Croizier, Éric Ajebo, Sébastien Cambier, Gil Boudet, Oluwaseun John Adeyemi, Ukadike Chris Ugbolue, Reza Bagheri, Guillaume T. Vallet, Jeannot Schmidt, Marion Trousselard, Frédéric Dutheil, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Pôle Urgences [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of the West of Scotland (UWS), Isfahan University of Technology, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Service Santé Travail Environnement [CHU Clermont-Ferrand]

Subjects
Quality of life, Work, Public health, Nutrition and Dietetics, Prevention, Health Personnel, Well-being, Nutrients, Circadian Rhythm, Diet, nutrients, work, well-being, quality of life, prevention, public health, Work Schedule Tolerance, [SCCO.PSYC]Cognitive science/Psychology, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Energy Intake, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract

Despite the consequences of night-shift work, the diet of night-shift workers has not been widely studied. To date, there are no studies related to food intake among emergency healthcare workers (HCWs). We performed a prospective observational study to assess the influence of night work on the diet of emergency HCWs. We monitored 24-h food intake during a day shift and the consecutive night, and during night work and the daytime beforehand. We analyzed 184 emergency HCWs’ food intakes. Emergency HCWs had 14.7% lower (−206 kcal) of their 24-h energy intake during night shifts compared to their day-shift colleagues (1606.7 ± 748.2 vs. 1400.4 ± 708.3 kcal, p = 0.049) and a 16.7% decrease in water consumption (1451.4 ± 496.8 vs. 1208.3 ± 513.9 mL/day, p = 0.010). Compared to day shifts, night-shift had 8.7% lower carbohydrates, 17.6% proteins, and 18.7% lipids. During the night shift the proportion of emergency HCWs who did not drink for 4 h, 8 h and 12 h increased by 20.5%, 17.5%, and 9.1%, respectively. For those who did not eat for 4 h, 8 h and 12 h increased by 46.8%, 27.7%, and 17.7%, respectively. A night shift has a huge negative impact on both the amount and quality of nutrients consumed by emergency healthcare workers.

Published
2022

39. The serotonin 2B receptor is required in neonatal microglia to limit neuroinflammation and sickness behavior in adulthood

Author

Christopher N. Parkhurst, Imane Moutkine, Fanny Etienne, Anne Roumier, Franck Verdonk, Silvina L. Diaz, Ivana D’Andrea, Luc Maroteaux, Sophie M. Banas, Marta Kolodziejczak, Catherine Béchade, Wenbiao B Gan, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), New York University School of Medicine (NYU), New York University School of Medicine, and NYU System (NYU)-NYU System (NYU)

Subjects
0301 basic medicine, Lipopolysaccharides, LPS, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, microglia, Biology, 5-HT2B receptor, neuroinflammation, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, 0302 clinical medicine, Immune system, Receptor, Serotonin, 5-HT2B, Weight Loss, medicine, Animals, Receptor, sickness syndrome, Sickness behavior, Neuroinflammation, 5-HT receptor, Illness Behavior, Innate immune system, Microglia, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 3. Good health, serotonin, Mice, Inbred C57BL, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, medicine.anatomical_structure, Neurology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Immunology, Neuroinflammatory Diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030217 neurology & neurosurgery
Abstract

International audience; Severe peripheral infections induce an adaptive sickness behavior and an innate immune reaction in various organs including the brain. On the long term, persistent alteration of microglia, the brain innate immune cells, is associated with an increased risk of psychiatric disorders. It is thus critical to identify genes and mechanisms controlling the intensity and duration of the neuroinflammation induced by peripheral immune challenges. We tested the hypothesis that the 5-HT2B receptor, the main serotonin receptor expressed by microglia, might represent a valuable candidate. First, we observed that Htr2b-/- mice, knock-out for the 5-HT2B receptor gene, developed, when exposed to a peripheral lipopolysaccharide (LPS) challenge, a stronger weight loss compared to wild-type mice; in addition, comparison of inflammatory markers in brain, 4 and 24 hr after LPS injection, showed that Htr2b deficiency leads to a prolonged neuroinflammation. Second, to assess the specific contribution of the microglial 5-HT2B receptor, we investigated the response to LPS of conditional knock-out mice invalidated for Htr2b in microglia only. We found that deletion of Htr2b in microglia since birth is sufficient to cause enhanced weight loss and increased neuroinflammatory response upon LPS injection at adult stage. In contrast, mice deleted for microglial Htr2b in adulthood responded normally to LPS, revealing a neonatal developmental effect. These results highlight the role of microglia in the response to a peripheral immune challenge and suggest the existence of a developmental, neonatal period, during which instruction of microglia through 5-HT2B receptors is necessary to prevent microglia overreactivity in adulthood.

Published
2020

40. Auto-deconvolution and molecular networking of gas chromatography-mass spectrometry data

Author

Ilaria Belluomo, Morgan Panitchpakdi, Aleksandr Smirnov, Mélissa Nothias-Esposito, Alexey V. Melnik, Gaud Dervilly, Rachel J. Dutton, Adolfo Amézquita, Vasilis Vasiliou, Zheng Zhang, Daniel Petras, Carrie D. Nicora, Audrey Poirier, James T. Morton, Ivan Laponogov, George B. Hanna, Sneha P. Couvillion, Biswapriya B. Misra, Robin Schmid, Wout Bittremieux, Raphaël Lugan, Brooke A. Anderson, Yann Guitton, Chris Callewaert, Kenneth L. Jones, Robert A. Quinn, Rob Knight, Larisa N. Kulikova, Itzhak Mizrahi, Erika M. Zink, Mabel Gonzalez, Sophie L. F. Doran, Rachel Gregor, Pauline Le Boulch, Kelem Gashu, Xiuxia Du, Michael M. Meijler, Kirill Veselkov, Chao Song, Elizabeth Humston-Fulmer, Noga Sikron Persi, Justin J. J. van der Hooft, Dennis Veselkov, Monica Guma, Kathleen Dorrestein, Saleh Alseekh, Roxana Coras, Chiara Carazzone, Thomas O. Metz, Aaron Fait, Andrea Georgina Albarracín Orio, Alexander A. Aksenov, Jose U. Scher, Andrea M. Smania, Bruno Le Bizec, Stav Eyal, Dinesh Kumar Barupal, Pieter C. Dorrestein, Alisdair R. Fernie, Reza Mirnezami, S. Prévost, Louis-Félix Nothias, Meagan C. Burnet, Viatcheslav B. Artaev, Mingxun Wang, Katherine N. Maloney, Julia Manasson, Madeleine Ernst, Roman S. Borisov, Amina Bouslimani, The Vodafone Foundation, National Institutes of Health, Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Collaborative Mass Spectrometry Innovation Center, Imperial College London, University of Antwerp (UA), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, University of North Carolina [Charlotte] (UNC), University of North Carolina System (UNC), Statens Serum Institut [Copenhagen], Wageningen University and Research [Wageningen] (WUR), Universidad de los Andes [Bogota] (UNIANDES), Center for Microbial Ecology and Technology (CMET), Universiteit Gent = Ghent University [Belgium] (UGENT), University of California, Flatiron Institute, Simons Foundation, Michigan State University [East Lansing], Michigan State University System, Universidad Católica de Córdoba, Universidad Nacional de Córdoba [Argentina], Pacific Northwest National Laboratory (PNNL), LECO Corporation, Ben-Gurion University of the Negev (BGU), Démarche intégrée pour l'obtention d'aliments de qualité (UMR QualiSud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Center of Plant Systems Biology and Biotechnology [Plovdiv] (CPSBB), Max Planck Institute of Molecular Plant Physiology (MPI-MP), Max-Planck-Gesellschaft, NHS Foundation Trust [London], The Royal Marsden, Yale School of Public Health (YSPH), University of Münster, A.V. Topchiev Institute of Petrochemical Synthesis (TIPS), Russian Academy of Sciences [Moscow] (RAS), and Peoples Friendship University of Russia [RUDN University] (RUDN)

Subjects
Computer science, Bioinformatics, [SDV]Life Sciences [q-bio], Biomedical Engineering, MESH: Algorithms, Bioengineering, S Agricultura (General), Mass spectrometry, computer.software_genre, METABOLOMICS, Applied Microbiology and Biotechnology, Gas Chromatography-Mass Spectrometry, Article, Matrix decomposition, 03 medical and health sciences, 0302 clinical medicine, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Bioinformatica, Metabolomics, Life Science, Animals, Humans, MESH: Metabolomics, Biology, 030304 developmental biology, Q Ciencia (General), 0303 health sciences, Science & Technology, MESH: Gas Chromatography-Mass Spectrometry, Workflow, Biotechnology & Applied Microbiology, Molecular networking, Molecular Medicine, Data mining, Deconvolution, Gas chromatography–mass spectrometry, Anura, computer, Engineering sciences. Technology, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Algorithms, Biotechnology, REPOSITORY, STANDARDS
Abstract

We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography–mass spectrometry (GC–MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC–MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization and quantifies the reproducibility of fragmentation patterns across samples., Fil: Aksenov, Alexander A. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Aksenov, Alexander A. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Laponogov, Ivan. South Kensington Campus. Imperial College London. Department of Surgery and Cancer; Reino Unido, Fil: Zhang, Zheng. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Doran, Sophie L. F. South Kensington Campus. Imperial College London. Department of Surgery and Cancer; Reino Unido, Fil: Belluomo, Ilaria. South Kensington Campus. Imperial College London. Department of Surgery and Cancer; Reino Unido, Fil: Veselkov, Dennis. Intelligify Limited. Reino Unido. South Kensington Campus. Imperial College. Department of Computing; Reino Unido, Fil: Bittremieux, Wout. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Bittremieux, Wout. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Bittremieux, Wout. University of Antwerp. Department of Computer Science; Belgica, Fil: Nothias, Louis Felix. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Nothias, Louis Felix. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Nothias-Esposito, Mélissa. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Nothias-Esposito, Mélissa. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Maloney, Katherine N. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Maloney, Katherine N. Point Loma Nazarene University. Department of Chemistry; Estados Unidos, Fil: Misra, Biswapriya B. Wake Forest School of Medicine. Section of Molecular Medicine. Department of Internal Medicine. Center for Precision Medicine; Estados Unidos, Fil: Melnik, Alexey V. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Smirnov, Aleksandr. University of North Carolina at Charlotte. Department of Bioinformatics and Genomics; Estados Unidos, Fil: Du, Xiuxia. University of North Carolina at Charlotte. Department of Bioinformatics and Genomics; Estados Unidos, Fil: Jones, Kenneth L. University of North Carolina at Charlotte. Department of Bioinformatics and Genomics; Estados Unidos, Fil: Dorrestein, Kathleen. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Dorrestein, Kathleen. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Panitchpakdi, Morgan. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Ernst, Madeleine. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Ernst, Madeleine. Statens Serum Institut. Danish Center for Neonatal Screening. Department of Congenital Disorders. Section for Clinical Mass Spectrometry; Dinamarca, Fil: van der Hooft, Justin J. J. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: van der Hooft, Justin J. J. Wageningen University. Bioinformatics Group; Países Bajos, Fil: Gonzalez, Mabel. Universidad de los Andes. Department of Chemistry; Colombia, Fil: Carazzone, Chiara. Universidad de los Andes. Department of Chemistry; Colombia, Fil: Amézquita, Adolfo. Universidad de los Andes. Department of Biological Sciences; Colombia, Fil: Callewaert, Chris. Center for Microbial Ecology and Technology; Belgica, Fil: Callewaert, Chris. University of California. Department of Pediatrics; Estados Unidos, Fil: Morton, James T. University of California. Department of Pediatrics; Estados Unidos, Fil: Morton, James T. Simons Foundation. Flatiron Institute. Center for Computational Biology; Estados Unidos, Fil: Quinn, Robert A. Michigan State University. Department of Biochemistry and Molecular Biology; Estados Unidos, Fil: Bouslimani, Amina. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Bouslimani, Amina. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Orio, Andrea Albarracín. Universidad Católica de Córdoba. IRNASUS. CONICET. Facultad de Ciencias Agropecuarias; Argentina, Fil: Petras, Daniel. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Petras, Daniel. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Smania, Andrea M. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica Ranwel Caputto; Argentina, Fil: Smania, Andrea M. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. CONICET; Argentina, Fil: Couvillion, Sneha P. Pacific Northwest National Laboratory. Biological Sciences Division; Estados Unidos, Fil: Burnet, Meagan C. Pacific Northwest National Laboratory. Biological Sciences Division; Estados Unidos, Fil: Nicora, Carrie D. Pacific Northwest National Laboratory. Biological Sciences Division; Estados Unidos, Fil: Zink, Erika. Pacific Northwest National Laboratory. Biological Sciences Division; Estados Unidos, Fil: Metz, Thomas O. Pacific Northwest National Laboratory. Biological Sciences Division; Estados Unidos, Fil: Artaev, Viatcheslav. LECO Corporation; Estados Unidos, Fil: Humston-Fulmer, Elizabeth. LECO Corporation; Estados Unidos, Fil: Gregor, Rachel. Ben-Gurion University of the Negev. Department of Chemistry and the National Institute for Biotechnology in the Negev; Israel, Fil: Meijler, Michael M. Ben-Gurion University of the Negev. Department of Chemistry and the National Institute for Biotechnology in the Negev; Israel, Fil: Mizrahi, Itzhak. Ben-Gurion University of the Negev. Department of Life Sciences and the National Institute for Biotechnology in the Negev; Israel, Fil: Eyal, Stav. Ben-Gurion University of the Negev. Department of Life Sciences and the National Institute for Biotechnology in the Negev; Israel, Fil: Anderson, Brooke. University of California. Division of Biological Sciences; Estados Unidos, Fil: Dutton, Rachel. University of California. Division of Biological Sciences; Estados Unidos, Fil: Lugan, Raphaël. Université d’Avignon et des Pays du Vaucluse, Agrosciences. UMR Qualisud; Francia, Fil: Boulch, Pauline Le. Université d’Avignon et des Pays du Vaucluse, Agrosciences. UMR Qualisud; Francia, Fil: Guitton, Yann. INRAe. Oniris. Laboratoire d’Etude des Résidus et Contaminants dans les Aliments (LABERCA); Francia, Fil: Prevost, Stephanie. INRAe. Oniris. Laboratoire d’Etude des Résidus et Contaminants dans les Aliments (LABERCA); Francia, Fil: Poirier, Audrey. INRAe. Oniris. Laboratoire d’Etude des Résidus et Contaminants dans les Aliments (LABERCA); Francia, Fil: Dervilly, Gaud. INRAe. Oniris. Laboratoire d’Etude des Résidus et Contaminants dans les Aliments (LABERCA); Francia, Fil: Le Bizec, Bruno. Oniris. Laboratoire d’Etude des Résidus et Contaminants dans les Aliments (LABERCA); Francia, Fil: Fait, Aaron. Ben Gurion University of the Negev. Sede Boqer Campus. The Jacob Blaustein Institutes for Desert Research. The French Associates Institute for Agriculture and Biotechnology of Dryland; Israel, Fil: Persi, Noga Sikron. Ben Gurion University of the Negev. Sede Boqer Campus. The Jacob Blaustein Institutes for Desert Research. The French Associates Institute for Agriculture and Biotechnology of Dryland; Israel, Fil: Song, Chao. Ben Gurion University of the Negev. Sede Boqer Campus. The Jacob Blaustein Institutes for Desert Research. The French Associates Institute for Agriculture and Biotechnology of Dryland; Israel, Fil: Gashu, Kelem. Ben Gurion University of the Negev. Sede Boqer Campus. The Jacob Blaustein Institutes for Desert Research. The French Associates Institute for Agriculture and Biotechnology of Dryland; Israel, Fil: Coras, Roxana. University of California. Department of Medicine. Division of Rheumatology; Estados Unidos, Fil: Guma, Monica. University of California. Department of Medicine. Division of Rheumatology; Estados Unidos, Fil: Manasson, Julia. New York University School of Medicine. Department of Medicine. Division of Rheumatology; Estados Unidos, Fil: Scher, Jose U. New York University School of Medicine. Department of Medicine. Division of Rheumatology; Estados Unidos, Fil: Barupal, Dinesh Kumar. Icahn School of Medicine at Mount Sinai. Department of Environmental Medicine and Public Health; Estados Unidos, Fil: Alseekh, Saleh. Max Planck Institute for Molecular Plant Physiology; Alemania, Fil: Alseekh, Saleh. Center of Plant Systems Biology and Biotechnology (CPSBB); Bulgaria, Fil: Fernie, Alisdair R. Max Planck Institute for Molecular Plant Physiology; Alemania, Fil: Fernie, Alisdair R. Center of Plant Systems Biology and Biotechnology (CPSBB); Bulgaria, Fil: Mirnezami, Reza. Royal Free Hospital NHS Foundation Trust. Department of Colorectal Surgery; Reino Unido, Fil: Vasiliou, Vasilis. Yale University. Yale School of Public Health. Department of Environmental Health Sciences; Estados Unidos, Fil: Schmid, Robin. University of Münster. Institute of Inorganic and Analytical Chemistry; Alemania, Fil: Borisov, Roman S. A.V. Topchiev Institute of Petrochemical Synthesis RAS; Rusia, Fil: Kulikova, Larisa N. Рeoples’ Friendship University of Russia (RUDN University); Rusia, Fil: Knight, Rob. University of California. Department of Pediatrics; Estados Unidos, Fil: Knight, Rob. University of California. UCSD Center for Microbiome Innovation; Estados Unidos, Fil: Knight, Rob. University of California. Department of Bioengineering; Estados Unidos, Fil: Wang, Mingxun. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Wang, Mingxun. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Hanna, George B. South Kensington Campus. Imperial College London. Department of Surgery and Cancer; Reino Unido, Fil: Dorrestein, Pieter C. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences; Estados Unidos, Fil: Dorrestein, Pieter C. University of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos, Fil: Dorrestein, Pieter C. University of California. Department of Pediatrics; Estados Unidos, Fil: Veselkov, Kirill. South Kensington Campus. Imperial College London. Department of Surgery and Cancer; Reino Unido

Published
2020

41. Experience and activity-dependent control of glucocorticoid receptors during the stress response in large-scale brain networks

Author

Margarita Arango-Lievano, Chadi Touma, Virginie Rappeneau, Freddy Jeanneteau, Damien Huzard, Michael J. Garabedian, Onno C. Meijer, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Osnabrück University of Applied Sciences (OS UAS), Hochschule Osnabrück, Einthoven Laboratory, Department of Medicine, Division of Endocrinology, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and freddy, jeanneteau

Subjects
Physiology, [SDV]Life Sciences [q-bio], Biology, Article, stress-related disorders, Synapse, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Glucocorticoid receptor, Receptors, Glucocorticoid, synapse, Bayesian brain, medicine, Humans, Epigenetics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Allostery, Glucocorticoids, Endocrine and Autonomic Systems, Stress-related disorders, Brain, Bayes Theorem, 030227 psychiatry, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Crosstalk (biology), Neuropsychology and Physiological Psychology, plasticity, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal transduction, Neuroscience, 030217 neurology & neurosurgery, Glucocorticoid, Stress, Psychological, epigenetic, medicine.drug, Hormone
Abstract

International audience; The diversity of actions of the glucocorticoid stress hormones among individuals and within organs, tissues and cells is shaped by age, gender, genetics, metabolism, and the quantity of exposure. However, such factors cannot explain the heterogeneity of responses in the brain within cells of the same lineage, or similar tissue environment, or in the same individual. Here, we argue that the stress response is continuously updated by synchronized neural activity on large-scale brain networks. This occurs at the molecular, cellular and behavioral levels by crosstalk communication between activity-dependent and glucocorticoid signaling pathways, which updates the diversity of responses based on prior experience. Such a Bayesian process determines adaptation to the demands of the body and external world. We propose a framework for understanding how the diversity of glucocorticoid actions throughout brain networks is essential for supporting optimal health, while its disruption may contribute to the pathophysiology of stress-related disorders, such as major depression, and resistance to therapeutic treatments.

Published
2020

42. Endocrine-disrupting chemicals: implications for human health

Author

Claire Philippat, Rémy Slama, Shoji F. Nakayama, Linda G. Kahn, Leonardo Trasande, New York University [New York] (NYU), NYU System (NYU), Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), National Institute for Environmental Studies [Tsukuba, Japan] (NIES), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), College of Global Public Health [New York], BARBAGALLO, Maïlys, and National Institute for Environmental Studies (NIES)

Subjects
Male, [SDE] Environmental Sciences, Health Status, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], MESH: Environmental Exposure, Physiology, 030209 endocrinology & metabolism, Endocrine Disruptors, Article, Childhood obesity, MESH: Occupational Exposure, MESH: Prenatal Exposure Delayed Effects, Impaired glucose tolerance, 03 medical and health sciences, Semen quality, 0302 clinical medicine, Endocrinology, Breast cancer, MESH: Pregnancy, Pregnancy, Occupational Exposure, Diabetes mellitus, Internal Medicine, medicine, Humans, 030212 general & internal medicine, MESH: Health Status, MESH: Humans, business.industry, Anogenital distance, Environmental Exposure, medicine.disease, MESH: Male, 3. Good health, MESH: Endocrine Disruptors, [SDV] Life Sciences [q-bio], Gestational diabetes, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Prenatal Exposure Delayed Effects, [SDE]Environmental Sciences, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract

International audience; Since reports published in 2015 and 2016 identified 15 probable exposure-outcome associations, there has been an increase in studies in humans of exposure to endocrine-disrupting chemicals (EDCs) and a deepened understanding of their effects on human health. In this Series paper, we have reviewed subsequent additions to the literature and identified new exposure-outcome associations with substantial human evidence. Evidence is particularly strong for relations between perfluoroalkyl substances and child and adult obesity, impaired glucose tolerance, gestational diabetes, reduced birthweight, reduced semen quality, polycystic ovarian syndrome, endometriosis, and breast cancer. Evidence also exists for relations between bisphenols and adult diabetes, reduced semen quality, and polycystic ovarian syndrome; phthalates and prematurity, reduced anogenital distance in boys, childhood obesity, and impaired glucose tolerance; organophosphate pesticides and reduced semen quality; and occupational exposure to pesticides and prostate cancer. Greater evidence has accumulated than was previously identified for cognitive deficits and attention-deficit disorder in children following prenatal exposure to bisphenol A, organophosphate pesticides, and polybrominated flame retardants. Although systematic evaluation is needed of the probability and strength of these exposure-outcome relations, the growing evidence supports urgent action to reduce exposure to EDCs.

Published
2020

43. Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing

Author

Shohei Murakami, Christophe Combadière, Federica Ferri, Giulia Ghinatti, Alexandre Boissonnas, Lamya Irbah, Paul-Henri Romeo, Nathalie Gault, Mayumi Ito, Christian F. Guerrero-Juarez, Rubén A. Ferrer, Elsa Treffeisen, Chae Ho Lim, Sandra Franz, Maksim V. Plikus, Philippe Mauffrey, Vilma Barroca, Isabelle Rombeau, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Microbiology and infectious diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of California [Irvine] (UCI), University of California, Leipzig University, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Cohen Children’s Medical Center, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [Irvine] (UC Irvine), University of California (UC), University of Pennsylvania, Centre d'Immunologie et des Maladies Infectieuses (CIMI), and Gestionnaire, Hal Sorbonne Université

Subjects
Phagocytosis, [SDV]Life Sciences [q-bio], Immunology, Human skin, Neogenesis, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Proto-Oncogene Proteins, Medicine, Humans, Health and Medicine, Wnt Signaling Pathway, Research Articles, 030304 developmental biology, Skin, Skin repair, 0303 health sciences, Wound Healing, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, integumentary system, business.industry, Macrophages, fungi, Wnt signaling pathway, food and beverages, SciAdv r-articles, Fibroblasts, medicine.disease, biology.organism_classification, 3. Good health, Fibronectin, Wnt Proteins, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Proteolysis, biology.protein, Cancer research, SFRP4, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract

Macrophages, renowned for clearance of debris and bacteria in the wound, can also uptake signaling inhibitors to promote fibrosis., Human and murine skin wounding commonly results in fibrotic scarring, but the murine wounding model wound-induced hair neogenesis (WIHN) can frequently result in a regenerative repair response. Here, we show in single-cell RNA sequencing comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity. In accordance, phagocytosis abrogation resulted in transient Wnt activity and a more regenerative healing. Phagocytosis of SFRP4 was integrin-mediated and dependent on the interaction of SFRP4 with the EDA splice variant of fibronectin. In the human skin condition hidradenitis suppurativa, phagocytosis of SFRP4 by macrophages correlated with fibrotic wound repair. These results reveal that macrophages can modulate a key signaling pathway via phagocytosis to alter the skin wound healing fate.

Published
2020

44. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19

Author

Bastard, P., Rosen, L. B., Zhang, Q., Michailidis, E., Hoffmann, H. -H., Zhang, Y., Dorgham, K., Philippot, Q., Rosain, J., Beziat, V., Manry, J., Shaw, E., Haljasmagi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A. A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A. N., Delmonte, O. M., Abers, M. S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R. P., Vasse, M., Smadja, D. M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D. C., Tangye, S. G., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M. C., Boisson-Dupuis, S., Rodriguez-Gallego, C., Vogt, G., Mogensen, T. H., Oler, A. J., Gu, J., Burbelo, P. D., Cohen, J. I., Biondi, A., Bettini, L. R., Dangio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E. S., Fusco, F., Ursini, M. V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G. L., Duval, X., Ghosn, J., Tsang, J. S., Goldbach-Mansky, R., Kisand, K., Lionakis, M. S., Puel, A., Zhang, S. -Y., Holland, S. M., Gorochov, G., Jouanguy, E., Rice, C. M., Cobat, A., Notarangelo, L. D., Abel, L., H. C., Su, Casanova, J. -L., Arias, A. A., Boisson, B., Boucherit, S., Bustamante, J., Chbihi, M., Chen, J., Chrabieh, M., Kochetkov, T., Le Voyer, T., Liu, D., Nemirovskaya, Y., Ogishi, M., Papandrea, D., Patissier, C., Rapaport, F., Roynard, M., Vladikine, N., Woollett, M., Zhang, P., Kashyap, A., Ding, L., Bosticardo, M., Wang, Q., Ochoa, S., Liu, H., Chauvin, S. D., Stack, M., Koroleva, G., Bansal, N., Dalgard, C. L., Snow, A. L., Abad, J., Aguilera-Albesa, S., Akcan, O. M., Darazam, I. A., Aldave, J. C., Ramos, M. A., Nadji, S. A., Alkan, G., Allardet-Servent, J., Allende, L. M., Alsina, L., Alyanakian, M. -A., Amador-Borrero, B., Amoura, Z., Antoli, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H. B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinieres, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, M., Borie, R., Bousfiha, A. A., Bouvattier, C., Boyarchuk, O., Bueno, M. R. P., Agra, J. J. C., Calimli, S., Capra, R., Carrabba, M., Casasnovas, C., Caseris, M., Castelle, M., Castelli, F., de Vera, M. C., Castro, M. V., Chalumeau, M., Charbit, B., Cheng, M. P., Clave, P., Clotet, B., Codina, A., Colkesen, F., Colobran, R., Comarmond, C., Corsico, A. G., Darley, D. R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Di Sabatino, A., Diehl, J. -L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M. H., Emiroglu, M., Erdeniz, E. H., Aytekin, S. E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M. F., Flores, C., Francois, B., Fumado, V., Solis, B. G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M. G., Girona-Alarcon, M., Goffard, J. -C., Gok, F., Gonzalez-Montelongo, R., Guerder, A., Gul, Y., Guner, S. N., Gut, M., Halwani, R., Hammarstrom, L., Hatipoglu, N., Hernandez-Brito, E., Holanda-Pena, M. S., Horcajada, J. P., Hraiech, S., Humbert, L., Iglesias, A. D., Inigo-Campos, A., Jamme, M., Arranz, M. J., Jordan, I., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K. K., Keles, S., Demirkol, Y. K., Klocperk, A., Krol, Z. J., Kuentz, P., Kwan, Y. W. M., Lagier, J. -C., Lau, Y. -L., Le Bourgeois, F., Leo, Y. -S., Lopez, R. L., Leung, D., Levin, M., Levy, M., Levy, R., Li, Z., Linglart, A., Lorenzo-Salazar, J. M., Louapre, C., Lubetzki, C., Luyt, C. -E., Lye, D. C., Mansouri, D., Marjani, M., Pereira, J. M., Martin, A., Pueyo, D. M., Marzana, I., Mathian, A., Matos, L. R. B., Matthews, G. V., Mege, J. -L., Melki, I., Meritet, J. -F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melian, A. M., Martinez, A. M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Munoz-Barrera, A., Nafati, C., Neves, J. F., L. F. P., Ng, Medina, Y. N., Cuadros, E. N., Gonzalo Ocejo-Vinyals, J., Orbak, Z., Oualha, M., Ozcelik, T., Hammarstrom, Q. P., Parizot, C., Pascreau, T., Paz-Artal, E., de Diego, R. P., Philippe, A., Philippota, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A. -S., Reisli, I., Ricart, P., Richard, J. -C., Rivet, N., Riviere, J. G., Blanch, G. R., Rodrigo, C., Rodriguez-Palmero, A., Romero, C. S., Rothenbuhler, A., Rozenberg, F., del Prado, M. Y. R., Riera, J. S., Sanchez, O., Sanchez-Ramon, S., Schluter, A., Schmidt, M., Schweitzer, C. E., Scolari, F., Sediva, A., Seijo, L. M., Sene, D., Senoglu, S., Seppanen, M. R. J., Ilovich, A. S., Shahrooei, M., Smadja, D., Sobh, A., Moreno, X. S., Sole-Violan, J., Soler, C., Soler-Palacin, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiottea, Y., Taupin, J. -L., Tavernier, S. J., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J. T., Trouillet-Assanta, S., Troya, J., Tucci, A., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., van Den Rym, A. M., Vandernoot, I., Vatansev, H., Velez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M. E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B. E., Yucel, F., Zannad, F., Zatz, M., Belota, A., Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M. G., Cazzaniga, M., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abela, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'Ortenzio, E., da Silveira, C., Debray, M. -P., Deplanque, D., Descamps, D., Desvallees, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Eloy, P., Enouf, V. V. E., Esperou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouenan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F. -X., Levy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J. C., Malvy, D., Mambert, M., Mentre, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puechal, O., Rosa-Calatrava, M., Rossignol, B., Roy, C., Schneider, M., Semaille, C., Mohammed, N. S., Tagherset, L., Tardivon, C., Tellier, M. -C., Teoule, F., Terrier, O., Timsit, J. -F., Treoux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Abelc, L., Alcover, A., Aschard, H., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Demangel, C., Deriano, L., Santo, J. D., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hercberg, S., Lantz, O., Patin, E., Pellegrini, S., Pol, S., Rausell, A., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M. -N., Albert, M. L., Alavoine, L., Amat, K. K. A., Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J. -L., Enouf, V., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Lucet, J. -C., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A. G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H. J., Bomers, M., Bos, L., Botta, M., de Brabander, J., Bree, G., Brouwer, M. C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M. P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S. M., Heunks, L., Hollmann, M. W., Horn, J., Hovius, J. W., de Jong, M. D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J. M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M. J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C. S., Stilma, W., Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, A. P. J., de Vries, H., van Vugt, M., Joost Wiersinga, W., Wouters, D., Zwinderman, A. H., Abelb, L., Muhsen, S. A., Al-Mulla, F., Anderson, M. S., Bogunovic, D., Bondarenko, A., Bryceson, Y., Bustamante, C. D., Butte, M., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M. A., Derisi, J. L., Desai, M., Drolet, B. A., Espinosa, S., Franco, J. L., Gregersen, P. K., Hagin, D., Heath, J., Henrickson, S. E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisanda, K., C. -L., Ku, Ling, Y., Lucas, C. L., Maniatis, T., Marodi, L., Milner, J. D., Mironska, K., Morio, T., Notarangeloa, L. D., Novelli, G., Novelli, A., O'Farrelly, C., Okada, S., Planas, A. M., Prando, C., Pujol, A., Renia, L., Renieri, A., Sancho-Shimizu, V., Sankaran, V., Barrett, K. S., Snow, A., Tangye, S., Turvey, S., Uddin, F., Uddin, M. J., Vazquez, S. E., von Bernuth, H., Washington, N., Zawadzki, P., Sua, H. C., Casanovaa, J. -L., Bastard, Paul, Rosen, Lindsey B, Zhang, Qian, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Zhang, Yu, Dorgham, Karim, Philippot, Quentin, Rosain, Jérémie, Béziat, Vivien, Manry, Jérémy, Shaw, Elana, Haljasmägi, Lii, Peterson, Pärt, Lorenzo, Lazaro, Bizien, Lucy, Trouillet-Assant, Sophie, Dobbs, Kerry, de Jesus, Adriana Almeida, Belot, Alexandre, Kallaste, Anne, Catherinot, Emilie, Tandjaoui-Lambiotte, Yacine, Le Pen, Jeremie, Kerner, Gaspard, Bigio, Benedetta, Seeleuthner, Yoann, Yang, Rui, Bolze, Alexandre, Spaan, András N, Delmonte, Ottavia M, Abers, Michael S, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Piemonti, Lorenzo, Ciceri, Fabio, Bilguvar, Kaya, Lifton, Richard P, Vasse, Marc, Smadja, David M, Migaud, Mélanie, Hadjadj, Jérome, Terrier, Benjamin, Duffy, Darragh, Quintana-Murci, Llui, van de Beek, Diederik, Roussel, Lucie, Vinh, Donald C, Tangye, Stuart G, Haerynck, Filomeen, Dalmau, David, Martinez-Picado, Javier, Brodin, Petter, Nussenzweig, Michel C, Boisson-Dupuis, Stéphanie, Rodríguez-Gallego, Carlo, Vogt, Guillaume, Mogensen, Trine H, Oler, Andrew J, Gu, Jingwen, Burbelo, Peter D, Cohen, Jeffrey, Biondi, Andrea, Bettini, Laura Rachele, D'Angio, Mariella, Bonfanti, Paolo, Rossignol, Patrick, Mayaux, Julien, Rieux-Laucat, Frédéric, Husebye, Eystein S, Fusco, Francesca, Ursini, Matilde Valeria, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Rossi, Camillo, Castagnoli, Riccardo, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Duval, Xavier, Ghosn, Jade, Tsang, John S, Goldbach-Mansky, Raphaela, Kisand, Kai, Lionakis, Michail S, Puel, Anne, Zhang, Shen-Ying, Holland, Steven M, Gorochov, Guy, Jouanguy, Emmanuelle, Rice, Charles M, Cobat, Aurélie, Notarangelo, Luigi D, Abel, Laurent, Su, Helen C, Casanova, Jean-Laurent, Meyts, Isabelle, Bastard, P, Rosen, L, Zhang, Q, Michailidis, E, Hoffmann, H, Zhang, Y, Dorgham, K, Philippot, Q, Rosain, J, Beziat, V, Manry, J, Shaw, E, Haljasmagi, L, Peterson, P, Lorenzo, L, Bizien, L, Trouillet-Assant, S, Dobbs, K, de Jesus, A, Belot, A, Kallaste, A, Catherinot, E, Tandjaoui-Lambiotte, Y, Le Pen, J, Kerner, G, Bigio, B, Seeleuthner, Y, Yang, R, Bolze, A, Spaan, A, Delmonte, O, Abers, M, Aiuti, A, Casari, G, Lampasona, V, Piemonti, L, Ciceri, F, Bilguvar, K, Lifton, R, Vasse, M, Smadja, D, Migaud, M, Hadjadj, J, Terrier, B, Duffy, D, Quintana-Murci, L, van de Beek, D, Roussel, L, Vinh, D, Tangye, S, Haerynck, F, Dalmau, D, Martinez-Picado, J, Brodin, P, Nussenzweig, M, Boisson-Dupuis, S, Rodriguez-Gallego, C, Vogt, G, Mogensen, T, Oler, A, Gu, J, Burbelo, P, Cohen, J, Biondi, A, Bettini, L, Dangio, M, Bonfanti, P, Rossignol, P, Mayaux, J, Rieux-Laucat, F, Husebye, E, Fusco, F, Ursini, M, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Castagnoli, R, Montagna, D, Licari, A, Marseglia, G, Duval, X, Ghosn, J, Tsang, J, Goldbach-Mansky, R, Kisand, K, Lionakis, M, Puel, A, Zhang, S, Holland, S, Gorochov, 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Leo, Y, Lopez, R, Leung, D, Levin, M, Levy, M, Levy, R, Li, Z, Linglart, A, Lorenzo-Salazar, J, Louapre, C, Lubetzki, C, Luyt, C, Lye, D, Mansouri, D, Marjani, M, Pereira, J, Martin, A, Pueyo, D, Marzana, I, Mathian, A, Matos, L, Matthews, G, Mege, J, Melki, I, Meritet, J, Metin, O, Meyts, I, Mezidi, M, Migeotte, I, Millereux, M, Mirault, T, Mircher, C, Mirsaeidi, M, Melian, A, Martinez, A, Morange, P, Mordacq, C, Morelle, G, Mouly, S, Munoz-Barrera, A, Nafati, C, Neves, J, Ng, L, Medina, Y, Cuadros, E, Gonzalo Ocejo-Vinyals, J, Orbak, Z, Oualha, M, Ozcelik, T, Hammarstrom, Q, Parizot, C, Pascreau, T, Paz-Artal, E, de Diego, R, Philippe, A, Philippota, Q, Planas-Serra, L, Ploin, D, Poissy, J, Poncelet, G, Pouletty, M, Quentric, P, Raoult, D, Rebillat, A, Reisli, I, Ricart, P, Richard, J, Rivet, N, Riviere, J, Blanch, G, Rodrigo, C, Rodriguez-Palmero, A, Romero, C, Rothenbuhler, A, Rozenberg, F, del Prado, M, Riera, J, Sanchez, O, Sanchez-Ramon, S, Schluter, A, Schmidt, M, Schweitzer, C, Scolari, F, Sediva, A, Seijo, L, Sene, D, Senoglu, S, Seppanen, M, Ilovich, A, Shahrooei, M, Sobh, A, Moreno, X, Sole-Violan, J, Soler, C, Soler-Palacin, P, Stepanovskiy, Y, Stoclin, A, Taccone, F, Tandjaoui-Lambiottea, Y, Taupin, J, Tavernier, S, Thumerelle, C, Tomasoni, G, Toubiana, J, Alvarez, J, Trouillet-Assanta, S, Troya, J, Tucci, A, Uzunhan, Y, Vabres, P, Valencia-Ramos, J, van Den Rym, A, Vandernoot, I, Vatansev, H, Velez-Santamaria, V, Viel, S, Vilain, C, Vilaire, M, Vincent, A, Voiriot, G, Vuotto, F, Yosunkaya, A, Young, B, Yucel, F, Zannad, F, Zatz, M, Belota, A, Foti, G, Bellani, G, Citerio, G, Contro, E, Pesci, A, Valsecchi, M, Cazzaniga, M, Bole-Feysot, C, Lyonnet, S, Masson, C, Nitschke, P, Pouliet, A, Schmitt, Y, Tores, F, Zarhrate, M, Abela, L, Andrejak, C, Angoulvant, F, Bachelet, D, Basmaci, R, Behillil, S, Beluze, M, Benkerrou, D, Bhavsar, K, Bompart, F, Bouadma, L, Bouscambert, M, Caralp, M, Cervantes-Gonzalez, M, Chair, A, Coelho, A, Couffignal, C, Couffin-Cadiergues, S, D'Ortenzio, E, da Silveira, C, Debray, M, Deplanque, D, Descamps, D, Desvallees, M, Diallo, A, Diouf, A, Dorival, C, Dubos, F, Eloy, P, Enouf, V, Esperou, H, Esposito-Farese, M, Etienne, M, Ettalhaoui, N, Gault, N, Gaymard, A, Gigante, T, Gorenne, I, Guedj, J, Hoctin, A, Hoffmann, I, Jaafoura, S, Kafif, O, Kaguelidou, F, Kali, S, Khalil, A, Khan, C, Laouenan, C, Laribi, S, Le, M, Le Hingrat, Q, Le Mestre, S, Le Nagard, H, Lescure, F, Levy, Y, Levy-Marchal, C, Lina, B, Lingas, G, Lucet, J, Malvy, D, Mambert, M, Mentre, F, Mercier, N, Meziane, A, Mouquet, H, Mullaert, J, Neant, N, Noret, M, Pages, J, Papadopoulos, A, Paul, C, Peiffer-Smadja, N, Petrov-Sanchez, V, Peytavin, G, Picone, O, Puechal, O, Rosa-Calatrava, M, Rossignol, B, Roy, C, Schneider, M, Semaille, C, Mohammed, N, Tagherset, L, Tardivon, C, Tellier, M, Teoule, F, Terrier, O, Timsit, J, Treoux, T, Tual, C, Tubiana, S, van der Werf, S, Vanel, N, Veislinger, A, Visseaux, B, Wiedemann, A, Yazdanpanah, Y, Abelc, L, Alcover, A, Aschard, H, Astrom, K, Bousso, P, Bruhns, P, Cumano, A, Demangel, C, Deriano, L, Santo, J, Dromer, F, Eberl, G, Enninga, J, Fellay, J, Gomperts-Boneca, I, Hasan, M, Hercberg, S, Lantz, O, Patin, E, Pellegrini, S, Pol, S, Rausell, A, Rogge, L, Sakuntabhai, A, Schwartz, O, Schwikowski, B, Shorte, S, Tangy, F, Toubert, A, Touvier, M, Ungeheuer, M, Albert, M, Alavoine, L, Amat, K, Bielicki, J, Bruijning, P, Burdet, C, Caumes, E, Charpentier, C, Coignard, B, Costa, Y, Damond, F, Dechanet, A, Delmas, C, Ecobichon, J, Frezouls, W, Houhou, N, Ilic-Habensus, E, Kikoine, J, Lebeaux, D, Leclercq, A, Lehacaut, J, Letrou, S, Manchon, P, Mandic, M, Meghadecha, M, Motiejunaite, J, Nouroudine, M, Piquard, V, Postolache, A, Quintin, C, Rexach, J, Roufai, L, Terzian, Z, Thy, M, Vignali, V, van Agtmael, M, Algera, A, van Baarle, F, Bax, D, Beudel, M, Bogaard, H, Bomers, M, Bos, L, Botta, M, de Brabander, J, Bree, G, Brouwer, M, de Bruin, S, Bugiani, M, Bulle, E, Chouchane, O, Cloherty, A, Elbers, P, Fleuren, L, Geerlings, S, Geerts, B, Geijtenbeek, T, Girbes, A, Goorhuis, B, Grobusch, M, Hafkamp, F, Hagens, L, Hamann, J, Harris, V, Hemke, R, Hermans, S, Heunks, L, Hollmann, M, Horn, J, Hovius, J, de Jong, M, Koning, R, van Mourik, N, Nellen, J, Paulus, F, Peters, E, van der Poll, T, Preckel, B, Prins, J, Raasveld, J, Reijnders, T, Schinkel, M, Schultz, M, Schuurman, A, Sigaloff, K, Smit, M, Stijnis, C, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A, van der Valk, M, Veelo, D, Vlaar, A, de Vries, H, van Vugt, M, Joost Wiersinga, W, Wouters, D, Zwinderman, A, Abelb, L, Iuti, F, Muhsen, S, Al-Mulla, F, Anderson, M, Bogunovic, D, Bondarenko, A, Bryceson, Y, Bustamante, C, Butte, M, Chakravorty, S, Christodoulou, J, Cirulli, E, Condino-Neto, A, Cooper, M, Derisi, J, Desai, M, Drolet, B, Espinosa, S, Franco, J, Gregersen, P, Hagin, D, Heath, J, Henrickson, S, Hsieh, E, Imai, K, Itan, Y, Karamitros, T, Kisanda, K, Ku, C, Ling, Y, Lucas, C, Maniatis, T, Marodi, L, Milner, J, Mironska, K, Morio, T, Notarangeloa, L, Novelli, G, Novelli, A, O'Farrelly, C, Okada, S, Planas, A, Prando, C, Pujol, A, Renia, L, Renieri, A, Sancho-Shimizu, V, Sankaran, V, Barrett, K, Turvey, S, Uddin, F, Uddin, M, Vazquez, S, von Bernuth, H, Washington, N, Zawadzki, P, Sua, H, Casanovaa, J, Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Rockefeller University [New York], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Tartu, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Lyon Immunopathology Federation (LIFe), Tartu University Hospital [Tartu, Estonia], Hôpital Foch [Suresnes], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Helix [San Mateo, CA], University Medical Center [Utrecht], IRCCS Ospedale San Raffaele [Milan, Italy], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Yale University School of Medicine, Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Paris (UP), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], McGill University Health Center [Montreal] (MUHC), Garvan Institute of Medical Research [Darlinghurst, Australia], University of New South Wales [Sydney] (UNSW), Ghent University Hospital, Hospital Universitario Mutua de Terrassa, Universitat de Barcelona (UB), Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute (IGTP), Universitat de Vic-Universitat Central de Catalunya, España, Institució Catalana de Recerca i Estudis Avançats (ICREA), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Hospital Universitario de Gran Canaria Dr Negrin, University Fernando Pessoa - UFP, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Aarhus University Hospital, Aarhus University [Aarhus], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Fondazione MBBM-Ospedale [Monza, Italie], San Gerardo Hospital, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bergen (UiB), Haukeland University Hospital, Consiglio Nazionale delle Ricerche [Napoli] (CNR), Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Brescia [Brescia], Università degli Studi di Pavia, Fondazione IRCCS Policlinico San Matteo, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Paris - UFR Médecine Paris Nord [Santé] (UP Médecine Paris Nord), Service d'Immunologie [CHU Pitié-Salpétrière], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), UM1 HG006504/HG/NHGRI NIH HHS/United States, P01 AI138938/AI/NIAID NIH HHS/United States, U19 AI111825/AI/NIAID NIH HHS/United States, U24 HG008956/HG/NHGRI NIH HHS/United States, MR/S032304/1/MRC_/Medical Research Council/United Kingdom, UKRI Future Leader's Fellowship, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANRS-COV05), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, the Institut Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. Samples from San Raffaele Hospital were obtained through the Covid-BioB project and by healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical laboratory and clinical research unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort Study Group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Milieu Intérieur Consortium was supported by the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Milieu Intérieur grant (ANR-10-LABX-69-01) (primary investigators: L.Q.-M. and D.Du.). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant 'DIGITAL COVID' (primary investigator: G.G.). S.G.T. is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia and a COVID19 Rapid Response Grant awarded by UNSW Sydney. C.R.-G. and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation RTC-2017-6471-1, AEI/FEDER, UE) and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). S.T.-A. and A.B. were supported by ANR-20-COVI-0064 (primary investigator: A.Be.). This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013,' by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and by a public grant overseen by the French National Research Agency (ANR) as part of the second Investissements d’Avenir program FIGHT-HF (reference no. ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence' (reference no. ANR-15-IDEX-04-LUE) (45), and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology, by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to F.R.-L.), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants from the Amsterdam Corona Research Fund, the Dr. C.J. Vaillant Fund, and the Netherlands Organization for Health Research and Development [ZonMw, NWO-Vici-Grant (grant no. 918·19·627 to D.v.d.B.)]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e comorbidita'). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. J.H. holds an Institut Imagine M.D.-Ph.D. fellowship from the Fondation Bettencourt Schueller. J.R. is supported by the INSERM Ph.D. program ('poste d’accueil Inserm'). P.Ba. was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the M.D.-Ph.D. program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association 'Turner et vous' for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K.K. was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (contract no. HHSN316201300006W/HHSN27200002 to MSC, Inc.), the Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data, and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support. Biomedical Advanced Research and Development Authority was supported under contract no. HHSO10201600031C (to J.H.). Financial support was provided by the National Institute of Allergy and Infectious Diseases (NIAID) K08AI135091, the Burroughs Wellcome Fund CAMS, the Clinical Immunology Society, and the American Academy of Allergy, Asthma, and Immunology, We thank the patients, their families, and healthy donors for placing their trust in us. We thank the French Incontinentia pigmenti association for their help and support. We thank Y. Nemirovskaya, D. Papandrea, M. Woollett, D. Liu, C. Rivalain, and C. Patissier for administrative assistance, D. Kapogiannis (National Institute on Aging) for providing healthy donor samples, and S. Xirasager, J. Barnett, X. Cheng, S. Weber, J. Danielson, B. Garabedian, and H. Matthews for their assistance in this study. We also thank R. Apps, B. Ryan, and Y. Belkaid of the CHI for their assistance. We thank the CRB-Institut Jérôme Lejeune, CRB-BioJeL, Paris, France, for their assistance. We thank M. C. García Guerrero, I. Erkizia, E. Grau, M. Massanella from IrsiCaixa AIDS Research Institute, Badalona, Spain, and J. Guitart from the Department of Clinical Genetics, University Hospital Germans Trias i Pujol, Badalona, Spain, for providing samples. We also thank J. Dalmau from IrsiCaixa for assistance, HGID Lab, NIAID-USUHS Immune Response to COVID Group, COVID Clinicians, COVID-STORM Clinicians, Imagine COVID Group, French COVID Cohort Study Group, The Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic, CoV-Contact Cohort: Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, Hélène Espérou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, Valérie Vignali, Benoit Visseaux, Yazdan Yazdanpanah, COVID Human Genetic Effort: Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, Andrés Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani​, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O'Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-Palacín, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova, Amsterdam UMC Covid-19 Biobank: Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P. J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek, HGID Lab: Andrés Augusto Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang, NIAID-USUHS Immune Response to COVID Group: Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow, COVID Clinicians: Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, Aurélie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan José Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Colkesen, Roger Colobran, Cloé Comarmond, Angelo G. Corsico, David Dalmau, David Ross Darley, Nicolas Dauby, Stéphane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria Fumadó, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mónica Girona-Alarcón, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Iolanda Jordan, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. Król, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Agnes Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, Clémence Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz-Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelik, Qiang Pan Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, Agustí Rodríguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-Ramón, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé-Violán, Catherine Soler, Pere Soler-Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini‬, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hulya Vatansev, Valentina Vélez-Santamaria, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot, COVID-STORM Clinicians: Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Imagine COVID Group: Christine Bole-Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate, French COVID Cohort Study Group: Laurent Abel, Claire Andrejak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadiergues, Eric D’ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent V. E. Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Yves Lévy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadj, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanan, The Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluis Quintana-Murci, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-20-COVI-0064,IFN-COVID19,Etude de la régulation de la réponse interferon de type I dans le control de l'infection par SARS-Cov2 et sa pathogènese(2020), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), Howard Hughes Medical Institute, Rockefeller University, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondazione Telethon, Ministère des Solidarités et de la Santé (France), European Commission, National Health and Medical Research Council (Australia), University of New South Wales (Australia), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Rosen, Lindsey B., Michailidis, Eleftherios, Haljasmägi, Liis, Spaan, András N., Quintana-Murci, Lluis, Beek, Diederik van der, Vinh, Donald C., Tangye, Stuart G., Martínez-Picado, Javier, Brodin, Peter, Nussenzweig, Michel C., Rodríguez-Gallego, Carlos, Mogensen, Trine, Oler, Andrew J., Burbelo, Peter D., Husebye, Eystein S., Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, ACS - Microcirculation, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Yale School of Medicine [New Haven, Connecticut] (YSM), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Garvan Institute of medical research, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), San Gerardo Hospital of Monza, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Pavia = University of Pavia (UNIPV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and J. Guitart from the Department of Clinical Genetics, University Hospital Germans Trias i Pujol, Badalona, Spain, for providing samples. We also thank J. Dalmau from IrsiCaixa for assistance HGID Lab, NIAID-USUHS Immune Response to COVID Group, COVID Clinicians, COVID-STORM Clinicians, Imagine COVID Group, French COVID Cohort Study Group, The Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic CoV-Contact Cohort: Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, Hélène Espérou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, Valérie Vignali, Benoit Visseaux, Yazdan Yazdanpanah COVID Human Genetic Effort: Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, Andrés Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani​, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O'Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-Palacín, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova Amsterdam UMC Covid-19 Biobank: Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P. J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek HGID Lab: Andrés Augusto Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang NIAID-USUHS Immune Response to COVID Group: Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow COVID Clinicians: Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, Aurélie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan José Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Colkesen, Roger Colobran, Cloé Comarmond, Angelo G. Corsico, David Dalmau, David Ross Darley, Nicolas Dauby, Stéphane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria Fumadó, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mónica Girona-Alarcón, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Iolanda Jordan, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. Król, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Agnes Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, Clémence Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz-Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelik, Qiang Pan Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, Agustí Rodríguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-Ramón, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé-Violán, Catherine Soler, Pere Soler-Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini‬, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hulya Vatansev, Valentina Vélez-Santamaria, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot COVID-STORM Clinicians: Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga Imagine COVID Group: Christine Bole-Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate French COVID Cohort Study Group: Laurent Abel, Claire Andrejak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadiergues, Eric D’ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent V. E. Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Yves Lévy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadj, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanan The Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluis Quintana-Murci, Bastard, Paul [0000-0002-5926-8437], Rosen, Lindsey B. [0000-0001-5894-3878], Zhang, Qian [0000-0002-9040-3289], Michailidis, Eleftherios [0000-0002-9907-4346], Dorgham, Karim [0000-0001-9539-3203], Béziat, Vivien [0000-0002-4020-824X], Manry, Jérémy [0000-0001-5998-2051], Shaw, Elana [0000-0001-9265-8026], Haljasmägi, Liis [0000-0001-7162-9808], Peterson, Pärt [0000-0001-6755-791X], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Trouillet-Assant, Sophie [0000-0001-6439-4705], Dobbs, Kerry [0000-0002-3432-3137], Belot, Alexandre [0000-0003-4902-5332], Kallaste, Anne [0000-0002-7492-667X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Le Pen, Jeremie [0000-0001-7025-9526], Kerner, Gaspard [0000-0003-0146-9428], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Bolze, Alexandre [0000-0001-7399-2766], Spaan, András N. [0000-0001-5981-7259], Aiuti, Alessandro [0000-0002-5398-1717], Lampasona, Vito [0000-0001-5162-8445], Piemonti, Lorenzo [0000-0002-2172-2198], Bilguvar, Kaya [0000-0002-7313-7652], Migaud, Mélanie [0000-0003-3062-1214], Hadjadj, Jérome [0000-0002-2520-3272], Terrier, Benjamin [0000-0001-6612-7336], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Beek, Diederik van der [0000-0002-4571-044X], Roussel, Lucie [0000-0001-5355-702X], Vinh, Donald C. [0000-0003-1347-7767], Tangye, Stuart G. [0000-0002-5360-5180], Dalmau, David [0000-0003-1936-478X], Martínez-Picado, Javier [0000-0002-4916-2129], Brodin, Peter [0000-0002-8103-0046], Nussenzweig, Michel C. [0000-0003-0592-8564], Boisson-Dupuis, Stéphanie [0000-0002-7115-116X], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Mogensen, Trine [0000-0002-1853-9704], Oler, Andrew J. [0000-0002-6310-0434], Burbelo, Peter D. [0000-0003-1717-048X], Cohen, Jeffrey [0000-0003-0238-7176], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Rieux-Laucat, Frédéric [0000-0001-7858-7866], Husebye, Eystein S. [0000-0002-7886-2976], Castagnoli, Riccardo [0000-0003-0029-9383], Licari, Amelia [0000-0002-1773-6482], Vougny, Marie-Christine, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, Etude de la régulation de la réponse interferon de type I dans le control de l'infection par SARS-Cov2 et sa pathogènese - - IFN-COVID192020 - ANR-20-COVI-0064 - COVID-19 - VALID, Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé - - AIROCovid192020 - ANR-20-COVI-0022 - COVID-19 - VALID, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anesthésiologie et soins intensifs [CHU Pitié-Salpêtrière], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Paris Diderot - Paris 7 - UFR Lettres, Arts, Langues, Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service d'immunologie [CHU Pitié-Salpétrière], Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The 'Milieu Intérieur' cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence 'Milieu Intérieur' Grant (ANR-10-LABX-69-01) (PI: L Quintana-Murci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant 'DIGITAL COVID' (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1, AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013', by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence', reference ANR-15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw, NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e comorbidita'). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program ('poste d’accueil Inserm'). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association 'Turner et vous' for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support., The Milieu Intérieur Consortium : Laurent Abel 1, Andres Alcover 2, Hugues Aschard 2, Kalla Astrom 3, Philippe Bousso 2, Pierre Bruhns 2, Ana Cumano 2, Caroline Demangel 2, Ludovic Deriano 2, James Di Santo 2, Françoise Dromer 2, Gérard Eberl 2, Jost Enninga 2, Jacques Fellay 4, Ivo Gomperts-Boneca 2, Milena Hasan 2, Serge Hercberg 5, Olivier Lantz 6, Hugo Mouquet 2, Etienne Patin 2, Sandra Pellegrini 2, Stanislas Pol 7, Antonio Rausell 8, Lars Rogge 2, Anavaj Sakuntabhai 2, Olivier Schwartz 2, Benno Schwikowski 2, Spencer Shorte 2, Frédéric Tangy 2, Antoine Toubert 9, Mathilde Touvier 10, Marie-Noëlle Ungeheuer 2, Matthew L. Albert 11*, Darragh Duffy 2*, Lluis Quintana-Murci 2* - 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine, Paris, France. 9Hôpital Saint-Louis, Paris, France. 10Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Bobigny, France. 11In Sitro, San Francisco, CA, USA. *Co-coordinators of The Milieu Intérieur Consortium. Additional information can be found at: www.milieuinterieur.fr/en., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC, Netherlands Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani​31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua D. Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa F. P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Dasman Diabetes Institute, Department of Genetics and Bioinformatics, Dasman, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Department, Faculty of Medicine and Pharmacy, Averroes University Hospital, LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Department of Pediatrics and Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco, Chan Zuckerberg Biohub, San Francisco, CA, USA. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Department of Biomedicine and Prevention, University of Rome 'Tor Vergata,' Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL - Hospital Duran I Reynals, Catalan Institution for Research and Advanced Studies (ICREA), CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63Medical Genetics, University of Siena, Italy, Genetica Medica, Azienda Ospedaliero-Universitaria Senese, GEN-COVID Multicenter Study, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Laboratory, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College, Centre for Precision Therapeutics, NeuroGen Children's Healthcare, Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, United Arab Emirates, The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 75Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, USA. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80The Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., ANR-10-LABX-0062,IBEID,Biologie Intégrative des Maladies Infectieuses Emergentes(2011), ANR-10-LABX-0020,NUMEV,Digital and Hardware Solutions and Modeling for the Environement and Life Sciences(2010), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Pulmonary medicine, Medical Microbiology and Infection Prevention, Internal medicine, Intensive care medicine, APH - Quality of Care, and Özçelik, Tayfun

Subjects
Male, COVID19, Immunoglobulin G, DISEASE, MESH: Antibodies, Neutralizing, 0302 clinical medicine, MESH: Interferon alpha-2, 80 and over, Medicine, Asymptomatic Infections, MESH: Immunoglobulin G, Aged, 80 and over, 0303 health sciences, MESH: Middle Aged, COVID Clinicians, MESH: Case-Control Studies, 3. Good health, Settore MED/03, 030220 oncology & carcinogenesis, MESH: Critical Illness, Interferon Type I, Science & Technology - Other Topics, Viral disease, MESH: Pandemics, [SDV.IMM] Life Sciences [q-bio]/Immunology, Critical Illness, Immunology, Pneumonia, Viral, Interferon alpha-2, HGID Lab, 03 medical and health sciences, Betacoronavirus, Genetics, Humans, MESH: SARS-CoV-2, COVID Human Genetic Effort, Aged, Autoantibodies, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Science & Technology, CYTOKINES, MESH: Adult, Pneumonia, medicine.disease, Antibodies, Neutralizing, COVID-STORM Clinicians, MESH: Pneumonia, Viral, Case-Control Studies, NIAID-USUHS Immune Response to COVID Group, MESH: Female, MESH: Interferon Type I, MESH: Coronavirus Infections, CHRONIC MUCOCUTANEOUS CANDIDIASIS, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Autoimmunity, CoV-Contact Cohort, MESH: Aged, 80 and over, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Medicine and Health Sciences, MESH: Autoantibodies, MESH: COVID-19, Online, Viral, Chronic mucocutaneous candidiasis, Imagine COVID Group, Amsterdam UMC Covid-19 Biobank, Neutralizing, Research Articles, MESH: Aged, Multidisciplinary, biology, Middle Aged, Multidisciplinary Sciences, Milieu Intérieur Consortium, MESH: Betacoronavirus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Coronavirus Infections, Research Article, Sciences exactes et naturelles, Adult, INTERFERON, General Science & Technology, PROTEINS, French COVID Cohort Study Group, MESH: Asymptomatic Infections, COVID-19, Pandemics, SARS-CoV-2, Asymptomatic, Antibodies, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Phenocopy, business.industry, R-Articles, Autoantibody, GAMMA, MESH: Male, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, biology.protein, 3111 Biomedicine, business
Abstract

HGID Lab Andrés Augusto Arias1,3, Bertrand Boisson1,2, Soraya Boucherit2, Jacinta Bustamante1,2, Marwa Chbihi2, Jie Chen1, Maya Chrabieh2, Tatiana Kochetkov1, Tom Le Voyer2, Dana Liu1, Yelena Nemirovskaya1, Masato Ogishi1, Dominick Papandrea1, Cécile Patissier2, Franck Rapaport1, Manon Roynard2, Natasha Vladikine2, Mark Woollett1, Peng Zhang1 1St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University. 2Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children. 3School of Microbiology and Group of Primary Immunodeficiencies, University of Antioquia UdeA, Medellin, Colombia., NIAID-USUHS Immune Response to COVID Group Anuj Kashyap1, Li Ding1, Marita Bosticardo1, Qinlu Wang2, Sebastian Ochoa1, Hui Liu1, Samuel D. Chauvin3, Michael Stack1, Galina Koroleva4, Neha Bansal5, Clifton L. Dalgard6,7, Andrew L. Snow8 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2Bioinformatics and Computational Biosciences Branch, NIAID Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 3Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 4NIH Center for Human Immunology, NIH, Bethesda, MD, USA. 5Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA. 6PRIMER, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 7Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 8Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Ahmed A. Bousfiha33, Claire Bouvattier34, Oksana Boyarchuk35, Maria Rita P. Bueno36, Jacinta Bustamante20, Juan José Cáceres Agra37, Semra Camli38, Ruggero Capra39, Maria Carrabba40, Carlos Casasnovas41, Marion Caseris42, Martin Castelle43, Francesco Castelli44, Martín Castillo de Vera45, Mateus V. Castro36, Emilie Catherinot46, Martin Chalumeau47, Bruno Charbit48, Matthew P. Cheng49, Père Clavé31, Bonaventura Clotet50, Anna Codina51, Fatih Colkesen52, Fatma Colkesen53, Roger Colobran 54, Cloé Comarmond55, Angelo G. Corsico56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Antonio Di Sabatino65, Jean-Luc Diehl66, Stephanie Dobbelaere67, Sophie Durand68, Waleed Eldars69, Mohamed Elgamal70, Marwa H. Elnagdy71, Melike Emiroglu72, Emine Hafize Erdeniz73, Selma Erol Aytekin74, Romain Euvrard75, Recep Evcen76, Giovanna Fabio40, Laurence Faivre77, Antonin Falck42, Muriel Fartoukh78, Morgane Faure79, Miguel Fernandez Arquero80, Carlos Flores81, Bruno Francois82, Victoria Fumadó83, Francesca Fusco84, Blanca Garcia Solis85, Pascale Gaussem86, Juana Gil-Herrera87, Laurent Gilardin88, Monica Girona Alarcon89, Mónica Girona-Alarcón89, Jean-Christophe Goffard90, Funda Gok91, Rafaela González-Montelongo92, Antoine Guerder93, Yahya Gul94, Sukru Nail Guner94, Marta Gut95, Jérôme Hadjadj96, Filomeen Haerynck97, Rabih Halwani98, Lennart Hammarström99, Nevin Hatipoglu100, Elisa Hernandez-Brito101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Sami Hraiech104, Linda Humbert105, Alejandro D. Iglesias106, Antonio Íñigo-Campos92, Matthieu Jamme107, María Jesús Arranz108, Iolanda Jordan109, Fikret Kanat110, Hasan Kapakli111, Iskender Kara112, Adem Karbuz113, Kadriye Kart Yasar114, Sevgi Keles115, Yasemin Kendir Demirkol116, Adam Klocperk117, Zbigniew J. Król118, Paul Kuentz119, Yat Wah M. Kwan120, Jean-Christophe Lagier121, Yu-Lung Lau122, Fleur Le Bourgeois60, Yee-Sin Leo123, Rafael Leon Lopez124, Daniel Leung122, Michael Levin125, Michael Levy60, Romain Lévy20, Zhi Li48, Agnes Linglart126, José M. Lorenzo-Salazar92, Céline Louapre127, Catherine Lubetzki127, Charles-Edouard Luyt128, David C. Lye129, Davood Mansouri130, Majid Marjani131, Jesus Marquez Pereira132, Andrea Martin133, David Martínez Pueyo134, Javier Martinez-Picado135, Iciar Marzana136, Alexis Mathian14, Larissa R. B. Matos36, Gail V. Matthews137, Julien Mayaux138, Jean-Louis Mège139, Isabelle Melki140, Jean-François Meritet141, Ozge Metin142, Isabelle Meyts143, Mehdi Mezidi144, Isabelle Migeotte145, Maude Millereux146, Tristan Mirault147, Clotilde Mircher68, Mehdi Mirsaeidi148, Abián Montesdeoca Melián149, Antonio Morales Martinez150, Pierre Morange151, Demence Mordacq105, Guillaume Morelle152, Stéphane Mouly13, Adrián Muñoz-Barrera92, Cyril Nafati153, João Farela Neves154, Lisa F. P. Ng155, Yeray Novoa Medina156, Esmeralda Nuñez Cuadros157, J. Gonzalo Ocejo-Vinyals158, Zerrin Orbak159, Mehdi Oualha20, Tayfun Özçelik160, Qiang Pan Hammarström161, Christophe Parizot138, Tiffany Pascreau162, Estela Paz-Artal163, Sandra Pellegrini48, Rebeca Pérez de Diego85, Aurélien Philippe164, Quentin Philippot78, Laura Planas-Serra165, Dominique Ploin166, Julien Poissy167, Géraldine Poncelet42, Marie Pouletty168, Paul Quentric138, Didier Raoult139, Anne-Sophie Rebillat68, Ismail Reisli169, Pilar Ricart170, Jean-Christophe Richard171, Nadia Rivet28, Jacques G. Rivière172, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego173, Agustí Rodríguez-Palmero174, Carolina Soledad Romero175, Anya Rothenbuhler176, Flore Rozenberg177, Maria Yolanda Ruiz del Prado178, Joan Sabater Riera15, Oliver Sanchez179, Silvia Sánchez-Ramón180, Agatha Schluter165, Matthieu Schmidt181, Cyril E. Schweitzer182, Francesco Scolari183, Anna Sediva184, Luis M. Seijo185, Damien Sene13, Sevtap Senoglu114, Mikko Seppänen186, Alex Serra Ilovich187, Mohammad Shahrooei62, David Smadja188, Ali Sobh189, Xavier Solanich Moreno15, Jordi Solé-Violán190, Catherine Soler191, Pere Soler-Palacín133, Yuri Stepanovskiy192, Annabelle Stoclin193, Fabio Taccone145, Yacine Tandjaoui-Lambiotte194, Jean-Luc Taupin195, Simon J. Tavernier196, Benjamin Terrier197, Caroline Thumerelle105, Gabriele Tomasoni198, Julie Toubiana47, Josep Trenado Alvarez199, Sophie Trouillet-Assant200, Jesús Troya201, Alessandra Tucci202, Matilde Valeria Ursini‬84, Yurdagul Uzunhan203, Pierre Vabres204, Juan Valencia-Ramos205, Ana Maria Van Den Rym85, Isabelle Vandernoot206, Hulya Vatansev207, Valentina Vélez-Santamaria41, Sébastien Viel166, Cédric Vilain208, Marie E. Vilaire68, Audrey Vincent34, Guillaume Voiriot209, Fanny Vuotto105, Alper Yosunkaya91, Barnaby E. Young123, Fatih Yucel210, Faiez Zannad211, Mayana Zatz36, Alexandre Belot212* 1University Hospital and Research Institute “Germans Trias i Pujol”, Badalona, Spain. 2Navarra Health Service Hospital, Pamplona, Spain. 3Division of Pediatric Infectious Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 4Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru. 6Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat Spain. 7Virology Research Center, National institutes of Tuberculosis and Lung diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8Division of Pediatric Infectious Diseases, Faculty of Medicine, Selcuk University, Konya, Turkey. 9Intensive care unit, Hôpital Européen, Marseille, France. 10Immunology Department, University Hospital 12 de Octubre. Research Institute imas12. Complutense University, Madrid, Spain. 11Hospital Sant Joan de Déu, Barcelona, Spain. 12Department of Biological Immunology, Necker Hospital for Sick Children, APHP and INEM, Paris, France. 13Internal medicine department, Hôpital Lariboisière, APHP; Université de Paris, Paris, France. 14Internal medicine department, Pitié-Salpétrière Hospital, Paris, France. 15Hospital Universitari de Bellvitge, Barcelona, Spain. 16Division of Clinical Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 17Joint Research Unit, Hospices Civils de Lyon-bio Mérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 18Hospital U. de Tarragona Joan XXIII. Universitat Rovira i Virgili (URV). IISPV, Tarragona, Spain. 19Private practice, Paris, France. 20Necker Hospital for Sick Children, AP-HP, Paris, France. 21Department of Infectious Diseases, CHU de Caen, Caen, France. 22Consorcio Hospital General Universitario, Valencia, Spain. 23The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 24Dept Urology, Nephrology, Transplantation, APHP-SU, Sorbonne Université, INSERM U 1082, Paris, France. 25Service de Médecine Intensive–Réanimation et Pneumologie, APHP Hôpital Pitié–Salpêtrière, Paris, France. 26Cruces University Hospital, Bizkaia, Spain. 27Paediatric Immunology and Vaccinology Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. 28Hematology, Georges Pompidou Hospital, APHP, Paris, France. 29Pediatric Infectious Diseases Unit. Instituto de Investigación 12 de Octubre (imas12). Hospital Universitario 12 de Octubre, Madrid, Spain. 30Department of Immunology, Motol University Hospital, 2nd Faculty of Medicine, Charles University, Department of Pediatrics, Thomayer’s Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. 31Centro de Investigación Biomédica en Red de Enfermedades Hepàticas y Digestivas (Ciberehd). Hospital de Mataró, Consorci Sanitari del Maresme, Mataró, Spain. 32Service de Pneumologie, Hopital Bichat, APHP, Paris, France. 33Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 34Endocrinology unit, APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 35Department of Children's Diseases and Pediatric Surgery, I.Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. 36Human Genome and stem-cell research center- University of São Paulo, São Paulo, Brazil. 37Hospital Insular, Las Palmas de Gran Canaria, Spain. 38Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Konya State Hospital, Konya, Turkey. 39MS Center, Spedali Civili, Brescia, Italy. 40Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 41Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. 42Hopital Robert Debré, Paris, France. 43Pediatric Immuno-hematology Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France. 44Department of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 45Doctoral Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 46Hôpital Foch, Suresnes, France. 47Necker Hospital for Sick Children, Paris University, AP-HP, Paris, France. 48Pasteur Institute, Paris, France. 49McGill University Health Centre, Montreal, Canada. 50University Hospital and Research Institute “Germans Trias i Pujol”, IrsiCaixa AIDS Research Institute, UVic-UCC, Badalona, Spain. 51Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Esplugues, Spain. 52Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 53Department of Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey. 54Hospital Universitari Vall d’Hebron, Barcelona, Spain. 55Pitié-Salpêtrière Hospital, Paris, France. 56Respiratory Diseases Division, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy. 57Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 58UNSW Medicine, St Vincent's Clinical School; Department of Thoracic Medicine, St Vincent's Hospital Darlinghurst, Sidney, Australia. 59CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium. 60Pediatric Intensive Care Unit, Robert-Debré University Hospital, APHP, Paris, France. 61Sorbonne Paris Nord, Hôpital Jean Verdier, APHP, Bondy, France. 62Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran. 63Centre de génétique humaine, CHU Besançon, Besançon, France. 64Sorbonne Université médecine and APHP Sorbonne université site Pitié-Salpêtrière, Paris, France. 65Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. 66Intensive Care unit, Georges Pompidou Hospital, APHP, Paris, France. 67Department of Pneumology, AZ Delta, Roeselare, Belgium. 68Institut Jérôme Lejeune, Paris, France. 69Department of Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 70Department of Chest, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 71Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 72Faculty of Medicine, Division of Pediatric Infectious Diseases, Selcuk University, Konya, Turkey. 73Division of Pediatric Infectious Diseases, Ondokuz Mayıs University, Samsun, Turkey. 74Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey. 75Centre Hospitalier Fleyriat, Bourg-en-Bresse, France. 76Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 77Centre de Génétique, CHU Dijon, Dijon, France. 78APHP Tenon Hospital, Paris, France. 79Sorbonne Universités, UPMC University of Paris, Paris, France. 80Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. 81Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain; Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, Spain. 82CHU Limoges and Inserm CIC 1435 & UMR 1092, Limoges, France. 83Infectious Diseases Unit, Department of Pediatrics, Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu, Spain; Universitat de Barcelona (UB), Barcelona, Spain. 84Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, IGB-CNR, Naples, Italy. 85Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 86Hematology, APHP, Hopital Européen Georges Pompidou and Inserm UMR-S1140, Paris, France. 87Hospital General Universitario and Instituto de Investigación Sanitaria "Gregorio Marañón", Madrid, Spain. 88Bégin military Hospital, Bégin, France. 89Pediatric Intensive Care Unit, Hospital Sant Joan de Déu, Barcelona, Spain. 90Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 91Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 92Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain. 93Assistance Publique Hôpitaux de Paris, Paris, France. 94Division of Allergy and Immunology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 95CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST); Universitat Pompeu Fabra (UPF), Barcelona, Spain. 96Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Paris, France. 97Ghent University Hospital, Ghent, Belgium. 98Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 99Department of Biosciences and Nutrition, SE14183, Huddinge, Karolinska Institutet, Stockholm, Sweden. 100Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 101Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 102IntensivenCare Unit. Marqués de Valdecilla Hospital, Santander, Spain. 103Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. 104Intensive care unit, APHM, Marseille, France. 105CHU Lille, Lille, France. 106Department of Pediatrics, Columbia University, New York, NY, USA. 107Centre hospitalier intercommunal Poissy Saint Germain en Laye, Poissy, France. 108Division of Respiratory Diseases, Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 109Hospital Sant Joan de Déu, Kids Corona Platfform, Barcelona, Spain. 110Selcuk University, Faculty of Medicine, Chest Diseases Department, Konya, Turkey. 111Division of Allergy and Immunology, Balikesir Ataturk City Hospital, Balikesir, Turkey. 112Division of Critical Care Medicine, Selcuk University, Faculty of Medicine, Konya, Turkey. 113Division of Pediatric Infectious Diseases, Prof. Dr. Cemil Tascıoglu City Hospital, Istanbul, Turkey. 114Departments of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 115Meram Medical Faculty, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 116Health Sciences University, Umraniye Education and Research Hospital, Istanbul, Turkey. 117Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic. 118Central Clinical Hospital of Ministry of the Interior and Administration in Warsaw, Warsaw, Poland. 119Oncobiologie Génétique Bioinformatique, PC Bio, CHU Besançon, Besançon, France. 120Paediatric Infectious Disease Unit, Hospital Authority Infectious Disease Center, Princess Margaret Hospital, Hong Kong (Special Administrative Region), China. 121Aix Marseille Univ, IRD, MEPHI, IHU Méditerranée Infection, Marseille, France. 122Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China. 123National Centre for Infectious Diseases, Singapore. 124Hospital Universitario Reina Sofía, Cordoba, Spain. 125Imperial College, London, England. 126Endocrinology and diabetes for children, AP-HP, Bicêtre Paris-Saclay hospital, Le Kremlin-Bicêtre, France. 127Neurology unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 128Intensive care unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 129National Centre for Infectious Diseases; Tan Tock Seng Hospital; Yong Loo Lin School of Medicine; Lee Kong Chian School of Medicine, Singapore. 130Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 131Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 132Hospital Sant Joan de Déu and University of Barcelona, Barcelona, Spain. 133Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. 134Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain. 135IrsiCaixa AIDS Research Institute, ICREA, UVic-UCC, Research Institute “Germans Trias i Pujol”, Badalona, Spain. 136Department of Laboratory, Cruces University Hospital, Barakaldo, Bizkaia, Spain. 137University of New South Wales, Australia. 138APHP Pitié-Salpêtrière Hospital, Paris, France. 139Aix-Marseille University, APHM, Marseille, France. 140Robert Debré Hospital, Paris, France. 141APHP Cohin Hospital, Paris, France. 142Necmettin Erbakan University Meram Faculty of Medicine Department of Pediatric Infectious Diseases, Konya, Turkey. 143University Hospitals Leuven, Leuven, Belgium. 144Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France. 145Hôpital Erasme, Brussels, Belgium. 146CH Gonesse, Gonesse, France. 147Vascular Medicine, Georges Pompidou Hospital, APHP, Paris, France. 148Division of Pulmonary and Critical Care, University of Miami, Miami, USA. 149Guanarteme Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 150Regional University Hospital of Malaga, Malaga, Spain. 151Aix-Marseille Université, Marseille, France. 152Department of General Paediatrics, Hôpital Bicêtre, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France. 153CHU de La Timone, Marseille, France. 154Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. 155Infectious Diseases Horizontal Technlogy Centre, A*STAR; Singapore Immunology Network, A*STAR, Singapore. 156Department of Pediatrics, Complejo Hospitalario Universitario Insular-Materno Infantil, Canarian Health System, Las Palmas de Gran Canaria, Spain. 157Regional Universitary Hospital of Malaga, Málaga, Spain. 158Hospital Universitario Marqués de Valdecilla, Santander, Spain. 159Ataturk University Medical Faculty, Erzurum, Turkey. 160Bilkent University, Department of Molecular Biology and Genetics, Ankara, Turkey. 161Department of Laboratory Medicine, Karolinska Institutet, SE14186, Stockholm, Sweden. 162L'Hôpital Foch, Suresnes, France. 163Department of Immunology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. 164APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 165Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona; CIBERER U759, ISCiii Madrid, Spain. 166Hospices Civils de Lyon, Lyon, France. 167Université de Lille, Inserm U1285, CHU Lille, Paris, France. 168Departement of General Pediatrics, University Hospital Robert Debré, APHP, Paris, France. 169Necmettin Erbakan University, Konya, Turkey. 170Germans Trias i Pujol Hospital, Badalona, Spain. 171Medical intensive care unit. Hopital de la Croix-Rousse. Hospices Civils de Lyon, Lyon, France. 172Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus., Barcelona, Spain. 173Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain, EU. University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. 174Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona, Spain. 175Consorcio Hospital General Universitario, Valencia, Spain. 176APHP Hôpitaux Universitaires Paris-Sud, Paris, France. 177Virology unit, Université de Paris, Cohin Hospital, APHP, Paris, France. 178Hospital San Pedro, Logroño, Spain. 179Respiratory medicine, Georges Pompidou Hospital, APHP, Paris, France. 180Dept. Immunology, Hospital Clínico San Carlos, Madrid, Spain. 181Service de Médecine Intensive Réanimation, Institut de Cardiologie, Hopital Pitié-Salpêtrière, Paris, France. 182CHRU de Nancy, Hôpital d'Enfants, Vandoeuvre, France. 183Chair of Nephrology, University of Brescia, Brescia, Italy. 184Department of Immunology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. 185Clínica Universidad de Navarra, Madrid, Spain. 186HUS Helsinki University Hospital, Children and Adolescents, Rare Disease Center, and Inflammation Center, Adult Immunodeficiency Unit, Majakka, Helsinki, Finland. 187Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain. 188Hopital Européen Georges Pompidou, Paris, France. 189Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 190Critical Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 191CHU de Saint Etienne, Saint-Priest-en-Jarez, France. 192Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 193Gustave Roussy Cancer Campus, Villejuif, France. 194Intensive Care Unit, Avicenne Hospital, APHP, Bobigny, France. 195Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, Paris University, Paris, France. 196Department of Internal Diseases and Pediatrics, Primary Immune Deficiency Research Lab, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium. 197Department of Internal Medicine, Université de Paris, INSERM, U970, PARCC, F-75015, Paris, France. 198First Division of Anesthesiology and Critical Care Medicine, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 199Intensive Care Department, Hospital Universitari MutuaTerrassa, Universitat Barcelona, Terrassa, Spain. 200Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 201Infanta Leonor University Hospital, Madrid, Spain. 202Hematology Department, ASST Spedali Civili di Brescia, Brescia, Italy. 203Pneumologie, Hôpital Avicenne, APHP, INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France. 204Dermatology unit, Laboratoire GAD, INSERM UMR1231 LNC, université de Bourgogne, Dijon, France. 205University Hospital of Burgos, Burgos, Spain. 206Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 207Department of Chest Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 208CHU de Caen, Caen, France. 209Sorbonne Université, Service de Médecine Intensive Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. 210General Intensive Care Unit, Konya Training and Research Hospital, Konya, Turkey. 211CHU de Nancy, Nancy, France. 212University of Lyon, CIRI, INSERM U1111, National referee centre RAISE, Pediatric Rheumatology, HFME, Hospices Civils de Lyon, Lyon, France. *Leader of the COVID-clinicians group., COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT., Imagine COVID Group Christine Bole-Feysot1, Stanislas Lyonnet1*, Cécile Masson1, Patrick Nitschke1, Aurore Pouliet1, Yoann Schmitt1, Frederic Tores1, Mohammed Zarhrate1 1Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cardiergues14, Eric D’ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent V. E. Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Treoux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22Rouen - SMIT, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d'Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28Bordeaux - SMIT, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Colombes - Louis Mourier - Gynécologie, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT; (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35hôpital la timone, Marseille, France. 36Paris - Bichat - SMIT, France., The Milieu Intérieur Consortium Laurent Abel1, Andres Alcover2, Hugues Aschard2, Kalla Astrom3, Philippe Bousso2, Pierre Bruhns2, Ana Cumano2, Caroline Demangel2, Ludovic Deriano2, James Di Santo2, Françoise Dromer2, Gérard Eberl2, Jost Enninga2, Jacques Fellay4, Ivo Gomperts-Boneca2, Milena Hasan2, Serge Hercberg5, Olivier Lantz6, Hugo Mouquet2, Etienne Patin2, Sandra Pellegrini2, Stanislas Pol7, Antonio Rausell8, Lars Rogge2, Anavaj Sakuntabhai2, Olivier Schwartz2, Benno Schwikowski2, Spencer Shorte2, Frédéric Tangy2, Antoine Toubert9, Mathilde Touvier10, Marie-Noëlle Ungeheuer2, Matthew L. Albert11*, Darragh Duffy2*, Lluis Quintana-Murci2* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine. 9Hôpital Saint-Louis, Paris, France. 10Université Paris 13, Paris, France. 11In Sitro. *Co-coordinators of the Milieu Intérieur Consortium. Additional information can be found at: https://www.pasteur.fr/labex/milieu-interieur., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cardièrgues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d'Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M'Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France . 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, BORDEAUX. 16Hôpital Hotel Dieu, APHP, Paris, France. 17ervice des explorations fonctionnelles, Hôpital Bichat- Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anne Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, O. Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno de Jong12, Rutger Koning4, Mourik van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Bennedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Netherlands. 3Experimental Immunology, Amsterdam UMC, Netherlands. 4Department of Neurology, Amsterdam UMC, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Netherlands. 7Department of Pathology, Amsterdam UMC, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Netherlands. 10Amsterdam UMC, THE NETHERLANDS Biobank Core Facility, Amsterdam UMC, Netherlands. 11Department of Radiology, Amsterdam UMC, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Netherlands. 18Department of Neurology, Amsterdam UMC, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani​31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University., Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco; Chan Zuckerberg Biohub, San Francisco, CA, United States. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID research lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Bambino Gesù Children's Hospital, Rome, Italy; Dept. Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy, Rome, Italy, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid 28046, Spain, EU, Madrid, Spain, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL- Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63University of Siena, Siena, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Lab, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children's Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, Dhaka, Bangladesh. 75Amsterdam UMC, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, United States. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62- IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit; funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The “Milieu Intérieur” cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence “Milieu Intérieur” Grant (ANR-10-LABX-69-01) (PI: L QuintanaMurci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant “DIGITAL COVID” (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health “Programme Hospitalier de Recherche Clinique Inter regional 2013”, by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d’Excellence”, reference ANR15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw; NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e comorbidita”). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program (“poste d’accueil Inserm”). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association “Turner et vous” for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support.

Published
2020

45. In situ maturation and tissue adaptation of type 2 innate lymphoid cell progenitors

Author

Remi Doucet-Ladeveze, Dominic Grün, Georg Gasteiger, David Voehringer, Daniela C. Hernández, Nina Peltokangas, Richard M. Locksley, Agnieszka M. Kabat, Josip S. Herman, Cornelia Symowski, Patrice Zeis, Rebecca Gentek, Alexander Y. Rudensky, Christin Friedrich, Marc Bajénoff, Konrad Knöpper, Mi Lian, Shlomo Elias, Xiying Fan, Chiara Romagnani, Bajenoff, Marc, Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, Julius-Maximilians-Universität Würzburg (JMU), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University of Freiburg [Freiburg], University of California [San Francisco] (UC San Francisco), University of California (UC), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [San Francisco] (UCSF), University of California, and Institute for Virology and Immunobiology [Würzburg, Germany]

Subjects
0301 basic medicine, Ontogeny, [SDV]Life Sciences [q-bio], Cell, single cell atlas, Inbred C57BL, ILC2, Mice, 0302 clinical medicine, T Cell Transcription Factor 1, Immunology and Allergy, Innate, Promyelocytic Leukemia Zinc Finger Protein, Lymphocytes, skin and connective tissue diseases, Lung, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Cultured, single-cell RNA-seq, Innate lymphoid cell, Cell Differentiation, Lymphoid Progenitor Cells, Phenotype, ILCP, Nippostrongylus Brasiliensis, Cell biology, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Single-Cell Analysis, Interleukin-18 Receptor alpha Subunit, Signal Transduction, bone marrow, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cells, Immunology, Innate lymphoid cells, Biology, Article, 03 medical and health sciences, Innate lymphoid cells (ILC), medicine, Genetics, Animals, Humans, Progenitor cell, Transcription factor, Progenitor, progenitors, Immunity, immune system development, Stem Cell Research, Immunity, Innate, tissue immunity, Mice, Inbred C57BL, body regions, 030104 developmental biology, Bone marrow, Transcription Factors
Abstract

Innate lymphoid cells (ILCs) are generated early during ontogeny and persist predominantly as tissue-resident cells. Here, we examined how ILCs are maintained and renewed within tissues. We generated a single cell atlas of lung ILC2s and found that Il18r1+ ILCs comprise circulating and tissue-resident ILC progenitors (ILCP) and effector-cells with heterogeneous expression of the transcription factors Tcf7 and Zbtb16, and CD103. Our analyses revealed a continuous differentiation trajectory from Il18r1+ ST2- ILCPs to Il18r- ST2+ ILC2s, which was experimentally validated. Upon helminth infection, recruited and BM-derived cells generated the entire spectrum of ILC2s in parabiotic and shield chimeric mice, consistent with their potential role in the renewal of tissue ILC2s. Our findings identify local ILCPs and reveal ILCP in situ differentiation and tissue adaptation as a mechanism of ILC maintenance and phenotypic diversification. Local niches, rather than progenitor origin, or the developmental window during ontogeny, may dominantly imprint ILC phenotypes in adult tissues.

Published
2020

46. The Confidence Database

Author

Alan L. F. Lee, Polina Arbuzova, Torin K. Clark, Nadia Haddara, Damian P. Birney, Tricia X. F. Seow, Gerit Pfuhl, Tzu Yu Hsu, Caroline Peters, Jason Samaha, Maxine T. Sherman, David Soto, Maël Lebreton, Michael Pereira, Manuel Rausch, Ji Won Bang, Fuat Balcı, Gabriel Weindel, Karolina M. Lempert, Sabina Gherman, Antonio Martin, Denis O'Hora, Ariel Zylberberg, Başak Akdoğan, Peter D. Kvam, Matt Jaquiery, Gabriel Reyes, Eleanor R. Palser, Marcin Koculak, Audrey Mazancieux, Joshua Calder-Travis, Jeroen J.A. van Boxtel, Andrey Chetverikov, Yalçın Akın Duyan, Chen Song, Liang Luo, Borysław Paulewicz, Medha Shekhar, Vincent de Gardelle, Saeedeh Sadeghi, Kit S. Double, Karen Davranche, Christina Koß, Nathan Faivre, Troy C. Dildine, Sze Chai Kwok, Marios G. Philiastides, Indrit Bègue, Marion Rouault, Kobe Desender, Marta Siedlecka, Zuzanna Skóra, Lauren Y. Atlas, Fernanda Prieto, Xinming Xu, Justin Kantner, Jiwon Yeon, Brian Maniscalco, David Aguilar-Lleyda, Futing Zou, Timothy F. Brady, Xiao Hu, Mahiko Konishi, Julian Matthews, Sai Sun, Sébastien Massoni, William T. Adler, Shuo Wang, Rachel N. Denison, Samuel Recht, Jérôme Sackur, Thibault Gajdos, Kaitlyn Fallow, Michał Wierzchoń, Daniel M. Merfeld, Chien Ming Lo, Elisa Filevich, Iñaki Iturrate, Marine Hainguerlot, Christoph T. Weidemann, Qun Ye, Regan M. Gallagher, Dobromir Rahnev, Georgia Institute of Technology [Atlanta], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Universiteit Gent = Ghent University [Belgium] (UGENT), Lingnan Normal University, Department of Psychology and Center for Neural Science, New York University, New York, NY, USA, Centre d'économie de la Sorbonne (CES), Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], Bernstein Center for Computational Neuroscience [Berlin], Humboldt-Universität zu Berlin, National Institutes of Health [Bethesda] (NIH), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Geneva University Hospitals and University of Geneva, School of Psychology, The University of Sydney, Department of Psychology (University of California San Diego), University of California [San Diego] (UC San Diego), University of California-University of California, Department of Experimental Psychology, University of Oxford, Oxford, UK, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Smead Aerospace Engineering Sciences, Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Department of Education, University of Oxford, Applied Economics, Cognitive Psychology, Koç University, Laboratoire de psychologie cognitive (LPC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Department of Psychology, University of Victoria, School of Psychology, University of Queensland, University of Queensland [Brisbane], Department of Experimental & Applied Psychology, Vrije Universiteit Amsterdam (VUPSY), Paris School of Economics (PSE), École des Ponts ParisTech (ENPC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom, The Feinstein Institute for Medical Research, Erasmus University Rotterdam, Graduate Institute of Mind, Brain and Consciousness, Taipei Medical University, Taipei, Taiwan, Capital Normal University [Beijing], California State University [Northridge] (CSUN), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Department of Psychology, University of Florida, Key Laboratory of Brain Functional Genomics (MOE & STCSM), School of Psychology and Cognitive Science, East China Normal University, Shanghai, China, Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Materials Science, East China Normal University, Swiss Center for Affective Science, University of Pennsylvania [Philadelphia], Collaborative Innovation Center of Assessment toward Basic Education Quality, Beijing (ENCICABEQ), Department of Bioengineering, University of California, Bureau d'Économie Théorique et Appliquée (BETA), Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), School of Psychological Sciences, Monash University, Ohio State University [Columbus] (OSU), National University of Ireland [Galway] (NUI Galway), University of California [San Francisco] (UCSF), University of California, University College of London [London] (UCL), SWPS University of Social Sciences and Humanities, Partenaires INRAE, Ecole Polytechnique Fédérale de Lausanne (EPFL), University of Glasgow, The Arctic University of Norway (UiT), Universidad del Desarrollo, Catholic University of Eichstätt-Ingolstadt (KU), Laboratoire des systèmes perceptifs (LSP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire d'informatique de l'École polytechnique [Palaiseau] (LIX), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Cornell University [New York], University of California [Santa Cruz] (UCSC), Trinity College Dublin, Sackler Ctr Consciousness Sci, Brighton, E Sussex, University of Sussex, Cardiff University, Basque Ctr Cognit Brain & Language, San Sebastian, Basque Fdn Sci, Ikerbasque, Bilbao, CALTECH, Div Biol, Pasadena, CALTECH, Div Computat & Neural Syst, Pasadena, Monash University [Melbourne], University of Canberra, West Virginia University [Morgantown], Swansea University, East China Normal University [Shangaï] (ECNU), University of Rochester [USA], The organization of the Confidence Database was supported by the National Institute of Mental Health under award number R56MH119189 to D.R., ANR-16-CE28-0002,ImpactMeta,impact de la métacognition sur le comportement(2016), ANR-16-ASTR-0014,MetaStress,Impact du stress sur la décision et la métacognition: applications en aéronautique(2016), Balcı, Fuat (ORCID 0000-0003-3390-9352 & YÖK ID 51269), Duyan, Yalçın Akın, Kvam, Peter D., Rahnev, Dobromir, Desender, Kobe, Lee, Alan L. F., Adler, William T., Aguilar-Lleyda, David, Akdoğan, Başak, Arbuzova, Polina, Atlas, Lauren Y., Bang, Ji Won, Bègue, Indrit, Birney, Damian P, Brady, Timothy F., Calder-Travis, Joshua, Chetverikov, Andrey, Clark, Torin K., Davranche, Karen, Denison, Rachel N., Dildine, Troy C., Double, Kit S., Faivre, Nathan, Fallow, Kaitlyn, Filevich, Elisa, Gajdos, Thibault, Gallagher, Regan M., de Gardelle, Vincent, Gherman, Sabina, Haddara, Nadia, Hainguerlot, Marine, Hsu, Tzu-Yu, Hu, Xiao, Iturrate, Iñaki, Jaquiery, Matt, Kantner, Justin, Koculak, Marcin, Konishi, Mahiko, Koß, Christina, Kwok, Sze Chai, Lebreton, Maël, Lempert, Karolina M., Ming Lo, Chien, Luo, Liang, Maniscalco, Brian, Martin, Antonio, Massoni, Sébastien, Matthews, Julian, Mazancieux, Audrey, Merfeld, Daniel M., O’Hora, Denis, Palser, Eleanor R., Paulewicz, Borysław, Pereira, Michael, Peters, Caroline, Philiastides, Marios G., Pfuhl, Gerit, Prieto, Fernanda, Rausch, Manuel, Recht, Samuel, Reyes, Gabriel, Rouault, Marion, Sackur, Jérôme, Sadeghi, Saeedeh, Samaha, Jason, Seow, Tricia X. F., Shekhar, Medha, Sherman, Maxine T., Siedlecka, Marta, Skóra, Zuzanna, Song, Chen, Soto, David, Sun, Sai, van Boxtel, Jeroen J. A., Wang, Shuo, Weidemann, Christoph T., Weindel, Gabriel, Wierzchoń, Michał, Xu, Xinming, Ye, Qun, Yeon, Jiwon, Zou, Futing, Zylberberg, Ariel, College of Social Sciences and Humanities, Department of Psychology, PSL Univ, Ecole Normale Super, Lab Syst Percetifs, Dept Etud Cognit,CNRS, PSL Univ, Ecole Normale Super, INSERM, Dept Etud Cognit,CNRS,EHESS, École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Humboldt University Of Berlin, Department of Psychology [Univ California San Diego] (Psycho - UC San Diego), University of California (UC)-University of California (UC), Radboud University [Nijmegen], University of Colorado [Boulder], Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), University of Florida [Gainesville] (UF), University of Pennsylvania, AgroParisTech-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of California [San Francisco] (UC San Francisco), University of California (UC), SWPS University of Social Sciences and Humanities (SWPS), The Arctic University of Norway [Tromsø, Norway] (UiT), University of California [Santa Cruz] (UC Santa Cruz), and Ikerbasque - Basque Foundation for Science

Subjects
Databases, Factual, SIGNAL-DETECTION, Computer science, Datasets as Topic, Social Sciences, Confidence, INSIGHT, computer.software_genre, Signal-detection, Choice, Availability, Recognition, Insight, Choice Behavior, [SCCO]Cognitive science, Behavioral Neuroscience, ddc:616.89, Mental Processes, 0302 clinical medicine, Software, insight, Task Performance and Analysis, Psychology, choice, media_common, 0303 health sciences, Thesaurus (information retrieval), Psychology, Biological, Database, Psychology, Experimental, Cognition, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 16. Peace & justice, CHOICE, Multidisciplinary Sciences, ddc:128.37, [SCCO.PSYC]Cognitive science/Psychology, VDP::Samfunnsvitenskap: 200::Psykologi: 260, Science & Technology - Other Topics, recognition, Life Sciences & Biomedicine, Adult, Psychometrics, Social Psychology, VDP::Social science: 200::Psychology: 260, media_common.quotation_subject, availability, MEDLINE, Experimental and Cognitive Psychology, Article, Databases, 03 medical and health sciences, Perception, Reaction Time, Humans, Set (psychology), Factual, 030304 developmental biology, Science & Technology, business.industry, Extramural, AVAILABILITY, Neurosciences, RECOGNITION, signal-detection, Psychology, biological, Multidisciplinary sciences, Psychology, experimental, ddc:616.8, Study, Neurosciences & Neurology, Metacognition, business, computer, 030217 neurology & neurosurgery
Abstract

Understanding how people rate their confidence is critical for the characterization of a wide range of perceptual, memory, motor and cognitive processes. To enable the continued exploration of these processes, we created a large database of confidence studies spanning a broad set of paradigms, participant populations and fields of study. The data from each study are structured in a common, easy-to-use format that can be easily imported and analysed using multiple software packages. Each dataset is accompanied by an explanation regarding the nature of the collected data. At the time of publication, the Confidence Database (which is available at ) contained 145 datasets with data from more than 8,700 participants and almost 4 million trials. The database will remain open for new submissions indefinitely and is expected to continue to grow. Here we show the usefulness of this large collection of datasets in four different analyses that provide precise estimations of several foundational confidence-related effects., NIH National Institute of Mental Health (NIMH)

Published
2020

47. Plasmacytoid Dendritic Cells and Type I Interferon Promote Extrafollicular B Cell Responses to Extracellular Self-DNA

Author

Jule Goike, Vanja Sisirak, Joseph Pucella, Krystal L. Ching, Justin Mehl, George Georgiou, William N. Voss, Oriana A. Perez, Boris Reizis, Chetna Soni, Lee Serpas, Gregory C. Ippolito, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Texas at Austin [Austin], Immunology from Concept and Experiments to Translation (ImmunoConcept), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)

Subjects
0301 basic medicine, Fluorescent Antibody Technique, Autoimmunity, Cell Communication, medicine.disease_cause, TLR7TLR9, Autoantigens, extrafollicular B cell response, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Mice, 0302 clinical medicine, systemic lupus erythematosus, Interferon, immune system diseases, Immunology and Allergy, Lupus Erythematosus, Systemic, Receptor, skin and connective tissue diseases, Mice, Knockout, B-Lymphocytes, 3. Good health, Cell biology, Infectious Diseases, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, plasmacytoid dendritic cells, 030220 oncology & carcinogenesis, Antibodies, Antinuclear, Interferon Type I, type I interferon, Disease Susceptibility, Antibody, medicine.drug, Immunology, CD40 Ligand, Biology, Article, 03 medical and health sciences, medicine, Animals, B cell, Endodeoxyribonucleases, TLR9, Germinal center, TLR7, DNA, Dendritic Cells, Germinal Center, Disease Models, Animal, 030104 developmental biology, Toll-Like Receptor 7, Toll-Like Receptor 9, anti-DNA antibodies, biology.protein, DNASE1L3, Biomarkers
Abstract

International audience; Class-switched antibodies to double-stranded DNA (dsDNA) are prevalent and pathogenic in systemic lupus erythematosus (SLE), yet mechanisms of their development remain poorly understood. Humans and mice lacking secreted DNase DNASE1L3 develop rapid anti-dsDNA antibody responses and SLE-like disease. We report that anti-DNA responses in Dnase1l3-/- mice require CD40L-mediated T cell help, but proceed independently of germinal center formation via short-lived antibody-forming cells (AFCs) localized to extrafollicular regions. Type I interferon (IFN-I) signaling and IFN-I-producing plasmacytoid dendritic cells (pDCs) facilitate the differentiation of DNA-reactive AFCs in vivo and in vitro and are required for downstream manifestations of autoimmunity. Moreover, the endosomal DNA sensor TLR9 promotes anti-dsDNA responses and SLE-like disease in Dnase1l3-/- mice redundantly with another nucleic acid-sensing receptor, TLR7. These results establish extrafollicular B cell differentiation into short-lived AFCs as a key mechanism of anti-DNA autoreactivity and reveal a major contribution of pDCs, endosomal Toll-like receptors (TLRs), and IFN-I to this pathway.

Published
2020

48. Critical care journals during the COVID-19 pandemic: challenges and responsibilities

Author

Jean-Louis Teboul, Jan Bakker, Timothy G. Buchman, Elie Azoulay, Samir Jaber, Peter J. Mazzone, Giuseppe Citerio, Laurent Brochard, Jean Louis Vincent, Neurointensive Care Unit, Ospedale S. Gerardo, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Toronto, Emory University [Atlanta, GA], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université libre de Bruxelles (ULB), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidemiology, MORNET, Dominique, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Citerio, G, Bakker, J, Brochard, L, Buchman, T, Jaber, S, Mazzone, P, Teboul, J, Vincent, J, and Azoulay, E

Subjects
2019-20 coronavirus outbreak, medicine.medical_specialty, Biomedical Research, Coronavirus disease 2019 (COVID-19), Critical Care, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pain medicine, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Pneumonia, Viral, MEDLINE, Critical Care and Intensive Care Medicine, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, COVID‑19, Anesthesiology, Pandemic, medicine, Humans, Critical care journals, 030212 general & internal medicine, Intensive care medicine, Pandemics, ComputingMilieux_MISCELLANEOUS, biology, business.industry, SARS-CoV-2, COVID-19, 030208 emergency & critical care medicine, [SDV.ETH] Life Sciences [q-bio]/Ethics, biology.organism_classification, 3. Good health, [SDV.ETH]Life Sciences [q-bio]/Ethics, Editorial, Periodicals as Topic, business, Coronavirus Infections, Editorial Policies
Abstract

International audience

Published
2020

49. Plasma and CSF biomarkers for the diagnosis of Alzheimer's disease in adults with Down syndrome: a cross-sectional study

Author

Maria Carmona-Iragui, Isabel Barroeta, Susana Fernández, Christophe Hirtz, Alberto Lleó, Laura Videla, Juan Fortea, Sylvain Lehmann, Olivia Belbin, Constance Delaby, Rafael Blesa, Mony J. de Leon, Jordi Pegueroles, Bessy Benejam, Daniel Alcolea, Aleksandra Maleska Maceski, Sebastián Videla, Laia Muñoz, Jordi Clarimón, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Hospital de la Santa Creu i Sant Pau, Fundació Catalana de Síndrome de Down [Barcelona], New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), and Institute of Health Carlos III, Fundació La Marató de TV3, Fundació Bancaria Obra Social La Caixa, Fundació Catalana Síndrome de Down, and Fundació Víctor Grífols i Lucas.

Subjects
Adult, Male, 0301 basic medicine, Down syndrome, medicine.medical_specialty, Population, Prodromal Symptoms, tau Proteins, Comorbidity, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Neurofilament Proteins, Internal medicine, medicine, Humans, Dementia, education, education.field_of_study, Amyloid beta-Peptides, business.industry, Area under the curve, Middle Aged, medicine.disease, 3. Good health, Cross-Sectional Studies, 030104 developmental biology, Biomarker (medicine), Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Down Syndrome, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Blood sampling
Abstract

International audience; BACKGROUND:Diagnosis of Alzheimer's disease in Down syndrome is challenging because of the absence of validated diagnostic biomarkers. We investigated the diagnostic performance of plasma and CSF biomarkers in this population.METHODS:We did a cross-sectional study of adults aged 18 years and older with Down syndrome enrolled in a population-based health plan in Catalonia, Spain. Every person with Down syndrome assessed in the health plan was eligible to enter the Down Alzheimer Barcelona Neuroimaging Initiative, and those with a plasma or CSF sample available were included in this study. Participants underwent neurological and neuropsychological examination and blood sampling, and a subset underwent a lumbar puncture. Adults with Down syndrome were classified into asymptomatic, prodromal Alzheimer's disease, or Alzheimer's disease dementia groups by investigators masked to biomarker data. Non-trisomic controls were a convenience sample of young (23-58 years) healthy people from the Sant Pau Initiative on Neurodegeneration. Amyloid-β (Aβ)1-40, Aβ1-42, total tau (t-tau), 181-phosphorylated tau (p-tau; only in CSF), and neurofilament light protein (NfL) concentrations were measured in plasma with a single molecule array assay and in CSF with ELISA. Plasma and CSF biomarker concentrations were compared between controls and the Down syndrome clinical groups. Diagnostic performance was assessed with receiver operating characteristic curve analyses between asymptomatic participants and those with prodromal Alzheimer's disease and between asymptomatic participants and those with Alzheimer's disease dementia.FINDINGS:Between Feb 1, 2013, and Nov 30, 2017, we collected plasma from 282 participants with Down syndrome (194 asymptomatic, 39 prodromal Alzheimer's disease, 49 Alzheimer's disease dementia) and 67 controls; CSF data were available from 94 participants (54, 18, and 22, respectively) and all 67 controls. The diagnostic performance of plasma biomarkers was poor (area under the curve [AUC] between 0·53 [95% CI 0·44-0·62] and 0·74 [0·66-0·82]) except for plasma NfL concentrations, which had an AUC of 0·88 (0·82-0·93) for the differentiation of the asymptomatic group versus the prodromal Alzheimer's disease group and 0·95 (0·92-0·98) for the asymptomatic group versus the Alzheimer's disease dementia group. In CSF, except for Aβ1-40 concentrations (AUC 0·60, 95% CI 0·45-0·75), all biomarkers had a good performance in the asymptomatic versus prodromal Alzheimer's disease comparison: AUC 0·92 (95% CI 0·85-0·99) for Aβ1-42, 0·81 (0·69-0·94) for t-tau, 0·80 (0·67-0·93) for p-tau, and 0·88 (0·79-0·96) for NfL. Performance of the CSF biomarkers was optimal in the asymptomatic versus Alzheimer's disease dementia comparison (AUC ≥0·90 for all except Aβ1-40 [0·59, 0·45-0·72]). Only NfL concentrations showed a strong correlation between plasma and CSF biomarker concentrations in participants with Down syndrome (rho=0·80; p

Published
2018

50. Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol

Author

Martine Dubois, Aurélie Capel, Laure Pierard, Elodie Coquan, Bénédicte Giffard, Bénédicte Clarisse, Sophie Gouérant, Natacha Heutte, Hélène Castel, Karim Fizazi, Philippe Bartélémy, Alexandra Leconte, Heidi Laviec, Florence Joly, Frédéric Di Fiore, Isabelle Léger, Marie Lange, Centre de recherche clinique [CHU Caen] (CRC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Unité de coordination en oncogériatrie de Basse-Normandie [Caen] (UCOG Basse-Normandie), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’études des transformations des activités physiques et sportives (CETAPS), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Unité de Recherche clinique [Caen], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), École nationale supérieure des sciences de l'information et des bibliothèques (ENSSIB), Université de Lyon, Service d'Oncologie Médicale, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d'Oncologie Médicale et d'Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de psycho-oncologie (UPO), Département Interdisciplinaire de Soins de Support aux Patients en Onco-hématologie [Gustave Roussy] (DISSPO), Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité d'Oncologie Digestive, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Service d'Oncologie médicale [CHU Caen], CHU Caen, This work is supported by the French Institut National du Cancer (InCA_9528) for the collection of data and by a specific donation from ASTELLAS., Eustache, Francis, and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Oncology, Quality of life, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Androgen deprivation therapy, 03 medical and health sciences, chemistry.chemical_compound, Prostate cancer, Study Protocol, 0302 clinical medicine, Internal medicine, Genetics, medicine, Clinical endpoint, Enzalutamide, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030212 general & internal medicine, Hormone therapy, ComputingMilieux_MISCELLANEOUS, Cognitive reserve, business.industry, Abiraterone acetate, Correction, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Ageing, chemistry, Adherence, 030220 oncology & carcinogenesis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Cognitive impairments
Abstract

Background New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for a metastatic CRPCa. Methods/design The Cog-Pro study is a multicentre longitudinal study including CRPCa patients ≥70 years old treated with NGHT (n = 134), control metastatic prostate cancer patients without castration resistance treated with first generation androgen deprivation therapy (n = 55), and healthy participants (n = 33), matched on age and education. Cognitive, geriatric and quality of life assessment and biological tests will be performed at baseline, 3, 6 and 12 months after start of the treatment (inclusion time). The primary endpoint is the proportion of elderly patients receiving a NGHT who will experience a decline in cognitive performances within 3 months after study enrollment. Secondary endpoints concern: autonomy, quality of life, anxiety, depression, cognitive reserve, adherence to hormone-therapy, comparison of the cognitive impact of 2 different NGHT (abiraterone acetate and enzalutamide), impact of co-morbidities and biological assessments. Discussion Evaluating, understanding and analyzing the incidence, severity of cognitive impairments and their impact on quality of life, autonomy and adherence in this group of patients with advanced disease is a challenge. This study should help to improve cancer care of elderly patients and secure the use of oral treatments as the risk of non-observance does exist. Our results will provide up-to date information for patients and caregivers on impact of these treatments on cognitive function in order to help the physicians in the choice of the treatment. Trial registration NCT02907372, registered: July 26, 2016.

Published
2017

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