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

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-Laurent2021-10-092021-10-092021-10-092021-08-0110.1126/sciimmunol.abl4340https://infoscience.epfl.ch/handle/20.500.14299/182090WOS:000695969700002Circulating 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 <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.ImmunologyImmunologymyasthenia-gravis patientsdistinct functionsantibodiesinterferonalphaautoimmunityantinuclearimmunitypatientAutoantibodies 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 deathstext::journal::journal article::research article