Bastard, PaulDanish Blood Donor StudyDanish CHGERigo Bonnin, RaúlHGID Lab University of Hong KongAmsterdam UMC Covid-19 Biobank InvestigatorsSt. James’s Hospital SARS CoV2 Interest groupPlanas Obradors, Anna M.CONSTANCES CohortCOVID Human Genetic EffortSolanich, Xavier3C-Dijon StudyMilieu Intérieur ConsortiumCerba HealthCareMorandeira-Rego, FranciscoEtablissement du Sang study groupNIAID Immune Response To Covid GroupCOVID-STORM Clinicians University of Hong KongNH-COVAIR Study GroupPujol Onofre, AuroraFrench COVID Cohort Study GroupCoV-Contact CohortImagine COVID GroupCasasnovas Pons, CarlosJordán García, Iolanda2021-10-042021-10-042021-08-192470-9468https://hdl.handle.net/2445/180396Circulating 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.26 p.application/pdfengcc by (c) Bastard, Paul et al., 2021http://creativecommons.org/licenses/by/3.0/es/COVID-19ImmunoglobulinesCOVID-19Immunoglobulinsinfo:eu-repo/semantics/article7205992021-10-01info:eu-repo/semantics/openAccess34413139