Bastard, P.Gervais, A.Le Voyer, T.Rosain, J.Philippot, Q.Manry, J.Michailidis, E.Hoffmann, H. 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. E.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. G.Lagier, J. C.Gentile, S.Rosen, L. B.Shaw, E.Morio, T.Tanaka, J.Dalmau, D.Tharaux, PL.Sene, D.Stepanian, A.Megarbane, B.Triantafyllia, V.Fekkar, A.Heath, J. R.Franco, JL.Anaya, J. M.Sole-Violan, J.Imberti, L.Biondi, A.Bonfanti, P.Castagnoli, R.Delmonte, O. M.Zhang, Y.Snow, A. L.Holland, S. M.Biggs, C. M.Moncada-Velez, M.Arias, A. A.Lorenzo, L.Boucherit, S.Coulibaly, B.Anglicheau, D.Planas, A. M.Haerynck, F.Duvlis, S.Nussbaum, R. L.Özçelik, TayfunKeles, S.Bousfiha, A. A.El Bakkouri, J.Ramirez-Santana, C.Paul, S.Pan-Hammarstrom, Q.Hammarstrom, L.Dupont, A.Kurolap, A.Metz, CN.Aiuti, A.Casari, G.Lampasona, V.Ciceri, F.Barreiros, L. A.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. G.Burrel, S.Duffy, D.Quintana-Murci, L.Klocperk, A.Kann, N. Y.Shcherbina, A.Lau, Y. L.Leung, D.Coulongeat, M.Marlet, J.Koning, R.Reyes, L. F.Chauvineau-Grenier, A.Venet, F.Monneret, G.Nussenzweig, MC.Arrestier, R.Boudhabhay, I.Baris-Feldman, H.Hagin, D.Wauters, J.Meyts, I.Dyer, A. H.Kennelly, SP.Bourke, N. M.Halwani, R.Sharif-Askari, N. S.Dorgham, K.Sallette, J.Sedkaoui, S. M.AlKhater, S.Rigo-Bonnin, R.Morandeira, F.Roussel, L.Vinh, DC.Ostrowski, SR.Condino-Neto, A.Prando, C.Bondarenko, A.Spaan, A. N.Gilardin, L.Fellay, J.Lyonnet, S.Bilguvar, K.Lifton, R. P.Mane, S.Anderson, M. S.Boisson, B.Beziat, V.Zhang, SY.Andreakos, E.Hermine, O.Pujol, A.Peterson, P.Mogensen, T. H.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. K.Piemonti, L.Rodriguez-Gallego, C.Notarangelo, LD.Su, H. C.Kisand, K.Okada, S.Puel, A.Jouanguy, E.Rice, C. M.Tiberghien, P.Zhang, Q.Cobat, A.Abel, L.Casanova, J. L.2022-01-272022-01-272021-08-20http://hdl.handle.net/11693/76825Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω 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-α and/or IFN-ω (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-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-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 individuals 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.EnglishArticle10.1126/sciimmunol.abl43402470-9468