Journal
SCIENCE
Volume 370, Issue 6515, Pages 423-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abd4585
Keywords
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Categories
Funding
- Howard Hughes Medical Institute
- Rockefeller University
- St. Giles Foundation
- National Institutes of Health (NIH) [R01AI088364]
- National Center for Advancing Translational Sciences (NCATS)
- NIH Clinical and Translational Science Award (CTSA) program [UL1 TR001866]
- Emergent Ventures
- Mercatus Center at George Mason University - National Human Genome Research Institute (NHGRI) [UM1HG006504, U24HG008956]
- French National Research Agency (ANR) under the Investments for the Future program [ANR-10-IAHU-01, ANR-10-LABX-62IBEID]
- French Foundation for Medical Research (FRM)
- FRM
- ANR GENCOVID project [ANRS-COV05]
- Square Foundation, Grandir -Fonds de solidarite pour l'enfance
- SCOR Corporate Foundation for Science
- University of Paris
- healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy [COVID-19 OSR-UniSR]
- Fondazione Telethon
- INSERM
- REACTing consortium
- French Ministry of Health
- European Commission [RECOVER WP 6]
- French Government's Investissement d'Avenir program, Laboratoire d'Excellence Milieu Interieur [ANR-10-LABX-69-01, PHRC-20-0375 COVID-19]
- National Health and Medical Research Council of Australia
- UNSW Sydney
- Instituto de Salud Carlos III [COV20_01333, COV20_01334]
- Spanish Ministry of Science and Innovation [RTC-2017-6471-1]
- AEI/FEDER
- Cabildo Insular de Tenerife [CGIEU0000219140]
- (Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19) [ANR-20-COVI-0064]
- French Ministry of Health Programme Hospitalier de Recherche Clinique Inter regional
- FEDER Lorraine
- French National Research Agency (ANR) as part of the second Investissements d'Avenir program FIGHT-HF [ANR-15-RHU-0004]
- French PIA project Lorraine Universite d'Excellence [ANR-15-IDEX-04-LUE, Lorrain BB-003300035]
- Fonds IMMUNOV, for Innovation in Immunopathology
- Agence National de la Recherche
- FAST Foundation (French Friends of Sheba Tel Hashomer Hospital)
- NIH [P01AI138398-S1, 2U19AI111825, R01AI091707-10S1]
- George Mason University Fast Grant
- G. Harold and Leila Y. Mathers Charitable Foundation
- Amsterdam Corona Research Fund
- Dr. C.J. Vaillant Fund
- Netherlands Organization for Health Research and Development [ZonMw] [918, 19]
- Division of Intramural Research of the National Institute of Dental Craniofacial Research
- National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Regione Lombardia, Italy
- Fondation Bettencourt Schueller
- INSERM Ph.D. program
- French Foundation for Medical Research [EA20170638020]
- (Fondation Bettencourt-Schueller)
- Fonds de la recherche en sante du Quebec clinician-scientist scholar program
- Estonian Research Council [PUT1367]
- NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch [HHSN316201300006W/HHSN27200002]
- Biomedical Advanced Research and Development Authority [HHSO10201600031C]
- National Institute of Allergy and Infectious Diseases (NIAID) [K08AI135091]
- Burroughs Wellcome Fund CAMS
- Clinical Immunology Society
- American Academy of Allergy
- UKRI [MR/S032304/1] Funding Source: UKRI
- Agence Nationale de la Recherche (ANR) [ANR-20-COVI-0064] Funding Source: Agence Nationale de la Recherche (ANR)
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Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-omega (IFN-omega) (13 patients), against the 13 types of IFN-alpha (36), or against 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 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for lifethreatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
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