1. Autoantibodies neutralizing type I IFNs are present in similar to 4\% of uninfected individuals over 70 years old and account for similar to 20\% of COVID-19 deaths
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Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J, Michailidis E, Hoffmann H, Eto S, Garcia-Prat M, Bizien L, Parra-Martinez A, Yang R, Haljasmagi L, Migaud M, Sarekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt C, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garcon P, Riviere J, Lagier J, Gentile S, Rosen L, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux P, Sene D, Stepanian A, Megarbane B, Triantafyllia V, Fekkar A, Heath J, Franco J, Anaya J, Sole-Violan J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte O, Zhang Y, Snow A, Holland S, Biggs C, Moncada-Velez M, Arias A, Lorenzo L, Boucherit S, Coulibaly B, Anglicheau D, Planas A, Haerynck F, Duvlis S, Nussbaum R, Ozcelik T, Keles S, Bousfiha A, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarstrom Q, Hammarstrom L, Dupont A, Kurolap A, Metz C, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros L, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye S, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann N, Shcherbina A, Lau Y, Leung D, Coulongeat M, Marlet J, Koning R, Reyes L, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig M, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer A, Kennelly S, Bourke N, Halwani R, Sharif-Askari N, Dorgham K, Sallette J, Sedkaoui S, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh D, Ostrowski S, Condino-Neto A, Prando C, Bondarenko A, Spaan A, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton R, Mane S, Anderson M, Boisson B, Beziat V, Zhang S, Andreakos E, Hermine O, Pujol A, Peterson P, Mogensen T, Rowen L, Mond J, Debette S, de Lamballerie X, Duval X, Mentre F, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen P, Piemonti L, Rodriguez-Gallego C, Notarangelo L, Su H, Kisand K, Okada S, Puel A, Jouanguy E, Rice C, Tiberghien P, Zhang Q, Cobat A, Abel L, Casanova J, HGID Lab, COVID Clinicians, COVID-STORM Clinicians, NIAID Immune Response Covid Grp, NH-COVAIR Study Grp, Danish CHGE, Danish Blood Donor Study, St Jamess Hosp Sars CoV2 Interest, French COVID Cohort Study Grp, Imagine COVID-Grp, Milieu Interieur Consortium, CoV-Contact Cohort, Amsterdam Umc Covid-19 Biobank Inv, COVID Human Genetic Efft, CONSTANCES Cohort, 3C-Dijon Study, Cerba HealthCare, Etab Sang Study Grp, and Acibadem University Dspace
- Abstract
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 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.
- Published
- 2021
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