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

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-Martínez A,Yang R,Haljasmägi L,Migaud M,Särekannu 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,Garçon P,Rivière 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,Solé-Violán J,Imberti L,Biondi A,Bonfanti P,Castagnoli R,Delmonte O,Zhang Y,Snow A,Holland S,Biggs C,Moncada-Vélez 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-Hammarström Q,Hammarström 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,Bonradenko A,Spaan A,Gilardin L,Fellay J,Lyonnet S,Bilguvar K,Lifton R,Mane S,Anderson M,Boisson B,Béziat V,Zhang S,Vandreakos E,Hermine O,Pujol A,Peterson P,Mogensen T,Rowen L,Mond J,Debette S,de Lamballerie X,Duval X,Mentré 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,Rodríguez-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

Source :

2021 Aoû 20

Pmid / DOI:

34413139

Abstract

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 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.Copyright © 2021, American Association for the Advancement of Science.

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