期刊
SCIENCE IMMUNOLOGY
卷 6, 期 62, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abl4340
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资金
- 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 Awards (CTSA) program [UL1 TR001866]
- Fast Grant from Emergent Ventures
- Mercatus Center at George Mason University
- Yale Center for Mendelian Genomics
- GSP Coordinating Center - National Human Genome Research Institute (NHGRI) [UM1HG006504, U24HG008956]
- Yale High Performance Computing Center [S10OD018521]
- Fisher Center for Alzheimer's Research Foundation
- Meyer Foundation
- JPB Foundation
- French National Research Agency (ANR) under the Investments for the Future program [ANR-10-IAHU-01]
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]
- French Foundation for Medical Research (FRM) [EQU201903007798]
- FRM
- ANR GENCOVID project [ANR-20-COVI-0003]
- ANRS Nord-Sud [ANRS-COV05]
- ANR GENVIR [ANR-20-CE93-003]
- ANR AABIFNCOV [ANR-20-CO11-0001]
- European Union [824110]
- Square Foundation
- Grandir-Fonds de solidarite pour l'Enfance
- Fondation du Souffle
- SCOR Corporate Foundation for Science
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- REACTing-INSERM
- University of Paris
- MD-PhD program of the Imagine Institute (Fondation Bettencourt Schueller)
- NIH [P01AI138398-S1, 2U19AI111825, R01AI091707-10S1]
- George Mason University Fast Grant
- G. Harold and Leila Y. Mathers Charitable Foundation
- INSERM
- REACTing consortium
- French Ministry of Health [PHRC 20-0424]
- French Ministry of Health
- European Commission [RECOVER WP 6]
- NIAID
- NIDCR, NIH [ZIA AI001270, 1ZIAAI001265]
- Agence Nationale de la Recherche [ANR-10-LABX-69-01]
- Estonian Research Council [PRG117, PRG377]
- Al Jalila Foundation Seed Grant, Dubai, UAE [AJF202019]
- University of Sharjah, UAE [CoV19-0307]
- National Health and Medical Research Council of Australia
- UNSW Sydney COVID Rapid Response Initiative Grant
- Regione Lombardia, Italy
- Instituto de Salud Carlos III [COV20/0968, PI17/00660]
- Biomedical Advanced Research and Development Authority [HHSO10201600031C]
- Japan Agency for Medical Research and Development, AMED [JP20fk0108531]
- ANR Flash COVID-19 program
- SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs
- Fondation pour la Recherche Medicale
- Caisse Nationale d'Assurance Maladie des Travailleurs Salaries
- Direction generale de la Sante
- Mutuelle Generale de l'Education Nationale (MGEN)
- Institut de la Longevite
- Conseils Regionaux of Aquitaine and Bourgogne
- Fondation de France
- Ministry of Research-INSERM Programme Cohortes et collections de donnees biologiques
- University of Bordeaux Initiative of Excellence
- National Cancer Institute, NIH [75N91019D00024, 75N91021F00001]
- FWO Fundamental Clinical Mandate [1833317N]
- European Regional Development Fund (ERDF)
- Instituto de Salud Carlos III (Spanish Ministry for Science and Innovation
- AEI/FEDER, UE) [RTC-2017-6471-1, COV20_01333, COV20_01334]
- Fundacion DISA [OA18/017, OA20/024]
- Cabildo Insular de Tenerife [CGIEU0000219140]
- Cabildo Insular de Tenerife (Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19)
- MSFHR Health Professional-Investigator Award
- European Union's Horizon 2020 research and innovation program (ATAC) [101003650]
- Society for the Relief of Disabled Children
- Croucher Foundation
- Cooperation Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX) [806-2018]
- Colciencias [713-2016, 111574455633]
- Czech Health Research Council [NU20-05-00282, NV18-05-00162]
- Ministry of Health, Czech Republic
- Program Project COVID-19 OSR-UniSR
- Ministero della Salute [COVID-2020-12371617]
- CSL Behring Chair of Primary Immunodeficiencies
- KU Leuven C1 grant [C16/18/007]
- VIB-GC PID grant
- FWO [G0C8517N, G0B5120N, G0E8420N]
- Jeffrey Modell Foundation
- European Union's Horizon 2020 research and innovation programme [948959]
- Hellenic Foundation for Research and Innovation (INTERFLU) [1574]
- Sao Paulo Research Foundation (FAPESP) [2020/09702-1]
- JBS SA [69004]
- Meath Foundation
- FRM [EA20170638020]
- Agence Nationale de la Recherche (ANR) [ANR-20-COVI-0003] Funding Source: Agence Nationale de la Recherche (ANR)
- European Research Council (ERC) [948959] Funding Source: European Research Council (ERC)
Autoantibodies neutralizing interferons are present in a significant percentage of critical COVID-19 patients, especially in older individuals, and their prevalence increases with age.
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.
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