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cc by (c) Bastard, Paul et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/180396

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

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Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 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 1,124 deceased patients (aged 20 days-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-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω 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 subjects 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-β 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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BASTARD, Paul, Danish Blood Donor Study, Danish CHGE, RIGO BONNIN, Raúl, HGID Lab University of Hong Kong, Amsterdam UMC Covid-19 Biobank Investigators, St. James’s Hospital SARS CoV2 Interest group, PLANAS OBRADORS, Anna m., CONSTANCES Cohort, COVID Human Genetic Effort, SOLANICH, Xavier, 3C-Dijon Study, Milieu Intérieur Consortium, Cerba HealthCare, MORANDEIRA-REGO, Francisco, Etablissement du Sang study group, NIAID Immune Response To Covid Group, COVID-STORM Clinicians University of Hong Kong, NH-COVAIR Study Group, PUJOL ONOFRE, Aurora, French COVID Cohort Study Group, CoV-Contact Cohort, Imagine COVID Group, CASASNOVAS PONS, Carlos, JORDÁN GARCÍA, Iolanda. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. _Science Immunology_. 2021. Vol. 6, núm. 62. [consulta: 24 de gener de 2026]. ISSN: 2470-9468. [Disponible a: https://hdl.handle.net/2445/180396]

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