Bastard, PaulGervais, AdrianLe Voyer, TomRosain, JeremiePhilippot, QuentinManry, JeremyMichailidis, EleftheriosHoffmann, Hans-HeinrichEto, ShoheiGarcia-Prat, MarinaBizien, LucyParra-Martinez, AlbaYang, RuiHaljasmagi, LiisMigaud, MelanieSarekannu, KaritaMaslovskaja, Juliade Prost, NicolasTandjaoui-Lambiotte, YacineLuyt, Charles-EdouardAmador-Borrero, BlancaGaudet, AlexandrePoissy, JulienMorel, PascalRichard, PascaleCognasse, FabriceTroya, JesusTrouillet-Assant, SophieBelot, AlexandreSaker, KahinaGarcon, PierreRiviere, Jacques G.Lagier, Jean-ChristopheGentile, StephanieRosen, Lindsey B.Shaw, ElanaMorio, TomohiroTanaka, JunkoDalmau, DavidTharaux, Pierre-LouisSene, DamienStepanian, AlainMegarbane, BrunoTriantafyllia, VasilikiFekkar, ArnaudHeath, James R.Franco, Jose LuisAnaya, Juan-ManuelSole-Violan, JordiImberti, LuisaBiondi, AndreaBonfanti, PaoloCastagnoli, RiccardoDelmonte, Ottavia M.Zhang, YuSnow, Andrew L.Holland, Steven M.Biggs, Catherine M.Moncada-Velez, MarcelaArias, Andres AugustoLorenzo, LazaroBoucherit, SorayaCoulibaly, BoubacarAnglicheau, DanyPlanas, Anna M.Haerynck, FilomeenDuvlis, SotirijaNussbaum, Robert L.Ozcelik, TayfunKeles, SevgiBousfiha, Ahmed A.El Bakkouri, JalilaRamirez-Santana, CarolinaPaul, StephanePan-Hammarstrom, QiangHammarstrom, LennartDupont, AnnabelleKurolap, AlinaMetz, Christine N.Aiuti, AlessandroCasari, GiorgioLampasona, VitoCiceri, FabioBarreiros, Lucila A.Dominguez-Garrido, ElenaVidigal, MateusZatz, Mayanavan de Beek, DiederikSahanic, SabinaTancevski, IvanStepanovskyy, YuriiBoyarchuk, OksanaNukui, YokoTsumura, MiyukiVidaur, LoretoTangye, Stuart G.Burrel, SoniaDuffy, DarraghQuintana-Murci, LluisKlocperk, AdamKann, Nelli Y.Shcherbina, AnnaLau, Yu-LungLeung, DanielCoulongeat, MatthieuMarlet, JulienKoning, RutgerReyes, Luis FelipeChauvineau-Grenier, AngeliqueVenet, FabienneMonneret, GuillaumeNussenzweig, Michel C.Arrestier, RomainBoudhabhay, IdrisBaris-Feldman, HagitHagin, DavidWauters, JoostMeyts, IsabelleDyer, Adam H.Kennelly, Sean P.Bourke, Nollaig M.Halwani, RabihSharif-Askari, Narjes SahebDorgham, KarimSallette, JeromeSedkaoui, Souad MehlalAlKhater, SuzanRigo-Bonnin, RaulMorandeira, FranciscoRoussel, LucieVinh, Donald C.Ostrowski, Sisse RyeCondino-Neto, AntonioPrando, CarolinaBondarenko, AnastasiiaSpaan, Andras N.Gilardin, LaurentFellay, JacquesLyonnet, StanislasBilguvar, KayaLifton, Richard P.Mane, ShrikantAnderson, Mark S.Boisson, BertrandBeziat, VivienZhang, Shen-YingAndreakos, EvangelosHermine, OlivierPujol, AuroraPeterson, PartMogensen, Trine H.Rowen, LeeMond, JamesDebette, Stephaniede Lamballerie, XavierDuval, XavierMentre, FranceZins, MarieSoler-Palacin, PereColobran, RogerGorochov, GuySolanich, XavierSusen, SophieMartinez-Picado, JavierRaoult, DidierVasse, MarcGregersen, Peter K.Piemonti, LorenzoRodriguez-Gallego, CarlosNotarangelo, Luigi D.Su, Helen C.Kisand, KaiOkada, SatoshiPuel, AnneJouanguy, EmmanuelleRice, Charles M.Tiberghien, PierreZhang, QianCobat, AurelieAbel, LaurentCasanova, Jean-LaurentLab, H. G. I. D.Clinicians, C. O. V. I. D.Clinicians, C. O. V. I. D.-S. T. O. R. M.Grp, N.I.A.I.D. Immune Response CovidGrp, N. H.-C.O.V.A.I.R. StudyDanish, C. H. G. E.Study, Danish Blood DonorInterest, St Jamess Hosp Sars CoV2Grp, French C.O.V.I.D. Cohort StudyCOVID-Grp, ImagineConsortium, Milieu InterieurCohort, CoV-ContactInv, Amsterdam Umc Covid-19 BiobankEfft, C.O.V.I.D. Human GeneticCohort, C. O. N. S. T. A. N. C. E. S.Study, 3C.-DijonHealthCare, CerbaGrp, Etab Sang Study2023-02-212023-02-212021-01-0110.1126/sciimmunol.abl4340https://hdl.handle.net/11443/2891http://dx.doi.org/10.1126/sciimmunol.abl4340Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mlin 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/mlin 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 yearsmean: 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 <70 years, 2.3\% between 70 and 80 years, and 6.3\% >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.ArticleWOS:000695969700002