Bastard, P.Rosen, L. B.Zhang, Q.Michailidis, E.Hoffmann, H.-H.Zhang, Y.Dorgham, K.Philippot, Q.Rosain, J.Béziat, V.Manry, J.Shaw, E.Haljasmägi, L.Peterson, P.Lorenzo, L.Bizien, L.Trouillet-Assant, S.Dobbs, K.Almeida de Jesus, A.Belot, A.Kallaste, A.Catherinot, E.Tandjaoui-Lambiotte, Y.Le Pen, J.Kerner, G.Bigio, B.Seeleuthner, Y.Yang, R.Bolze, A.Spaan, A. N.Delmonte, O. M.Abers, M. S.Aiuti, A.Casari, G.Lampasona, V.Piemonti, L.Ciceri, F.Bilguvar, K.Lifton, R. P.Vasse, M.Smadja, D. M.Migaud, M.Hadjadj, J.Terrier, B.Duffy, D.Quintana-Murci, L.van de Beek, D.Roussel, L.Vinh, D. C.Tangye, S. G.Haerynck, F.Dalmau, D.Martinez-Picado, J.Brodin, P.Nussenzweig, M. C.Boisson-Dupuis, S.Rodríguez-Gallego, C.Vogt, G.Mogensen, T. H.Oler, A. J.Gu, J.Burbelo, P. D.Cohen, J. I.Biondi, A.Bettini, L. R.D'Angio, M.Bonfanti, P.Rossignol, P.Mayaux, J.Rieux-Laucat, F.Husebye, E. S.Fusco, F.Ursini, M. V.Imberti, L.Sottini, A.Paghera, S.Quiros-Roldan, E.Rossi, C.Castagnoli, R.Montagna, D.Özçelik, TayfunLicari, A.Marseglia, G. L.Duval, X.Ghosn, J.Tsang, J. S.Goldbach-Mansky, R.Kisand, K.Lionakis, M. S.Puel, A.Zhang, S.- Y.Holland, S. M.Gorochov, G.Jouanguy, E.Rice, C. M.Cobat, A.Notarangelo, L. D.Abel, L.Su, H. C.Casanova, J. L.HGID LabNIAID-USUHS Immune Response to COVID GroupCOVID CliniciansCOVID-STORM CliniciansImagine COVID GroupFrench COVID Cohort Study GroupMilieu Intérieur ConsortiumCoV-Contact CohortAmsterdam UMC Covid-19 BiobankCOVID Human Genetic Effort2021-03-312021-03-3120201095-9203http://hdl.handle.net/11693/76058Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.EnglishArticle10.1126/science.abd4585