{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:13:05Z","timestamp":1791947585714,"version":"4.3.4"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"62","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2021,8,10]]},"abstract":"<jats:p>Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng\/ml; in plasma diluted 1:10) of IFN-\u03b1 and\/or IFN-\u03c9 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-\u03b1 and\/or IFN-\u03c9 (100 pg\/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients &gt;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-\u03b2. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-\u03b1 and\/or IFN-\u03c9 are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% &gt;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 &lt;70 years, 2.3% between 70 and 80 years, and 6.3% &gt;80 years. By contrast, auto-Abs neutralizing IFN-\u03b2 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.<\/jats:p>","DOI":"10.1126\/sciimmunol.abl4340","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T15:15:41Z","timestamp":1629386141000},"source":"Crossref","is-referenced-by-count":558,"title":["Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths"],"prefix":"10.1126","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5926-8437","authenticated-orcid":true,"given":"Paul","family":"Bastard","sequence":"first","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"University of Paris, Imagine Institute, Paris, France."},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-5787","authenticated-orcid":true,"given":"Adrian","family":"Gervais","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"University of Paris, Imagine Institute, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0630-8626","authenticated-orcid":true,"given":"Tom","family":"Le Voyer","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"University of Paris, Imagine Institute, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-161X","authenticated-orcid":true,"given":"J\u00e9r\u00e9mie","family":"Rosain","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"University of Paris, Imagine Institute, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Philippot","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"University of Paris, Imagine Institute, Paris, 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