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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Jérémy ManryPaul BastardAdrian GervaisTom Le VoyerJérémie RosainQuentin PhilippotEleftherios MichailidisHans-Heinrich HoffmannShohei EtoMarina Garcia-PratLucy BizienAlba Parra-MartínezJean-Laurent CasanovaLiis HaljasmägiMélanie MigaudKarita SärekannuJulia MaslovskajaNicolas de ProstYacine Tandjaoui-LambiotteCharles-Edouard LuytBlanca Amador-BorreroAlexandre GaudetJulien PoissyPascal MorelPascale RichardFabrice CognasseJesús Troya GarcíaSophie Trouillet-AssantAlexandre BelotKahina SakerPierre GarçonJacques G RivièreJean-Christophe LagierStéphanie GentileLindsey B RosenElana ShawTomohiro MorioJunko TanakaDavid DalmauPierre-Louis TharauxDamien SeneAlain StepanianBruno MégarbaneVasiliki TriantafylliaArnaud FekkarJames R HeathJosé Luis FrancoJuan-Manuel AnayaJordi Solé-ViolánLuisa ImbertiAndrea BiondiBonfanti PaoloRiccardo CastagnoliOttavia M DelmonteYu ZhangAndrew L SnowSteven M HollandCatherine M BiggsMarcela Moncada-VélezAndrés Augusto AriasLazaro LorenzoSoraya BoucheritDany AnglicheauAnna M PlanasFilomeen HaerynckSotirija DuvlisTayfun OzcelikSevgi KelesAhmed A BousfihaJalila El BakkouriCarolina Ramirez-SantanaStephane PaulQiang Pan-HammarströmLennart HammarströmAnnabelle DupontAlina KurolapChristine N MetzAlessandro AiutiGiorgio CasariVito LampasonaFabio CiceriLucila A BarreirosElena Dominguez-GarridoMateus VidigalMayana ZatzDiederik van de BeekSabina SahanicIvan TancevskiYurii StepanovskyyOksana BoyarchukYoko NukuiMiyuki TsumuraLoreto VidaurStuart G TangyeSonia BurrelDarragh DuffyLluis Quintana-MurciAdam KlocperkNelli Y KannAnna ShcherbinaYu-Lung LauDaniel LeungMatthieu CoulongeatJulien MarletRutger KoningLuis Felipe ReyesAngélique Chauvineau-GrenierFabienne VenetGuillaume MonneretMichel C NussenzweigRomain ArrestierIdris BoudhabhayHagit Baris-FeldmanDavid HaginJoost WautersIsabelle MeytsAdam H DyerSean P KennellyNollaig M BourkeRabih HalwaniFatemeh Saheb Sharif-AskariKarim DorghamJérôme SalletteSouad Mehlal SedkaouiSuzan AlKhaterRaúl Rigo-BonninFrancisco MorandeiraLucie RousselDonald C VinhChristian ErikstrupAntonio Condino-NetoCarolina PrandoAnastasiia BondarenkoAndrás N SpaanLaurent GilardinJacques FellayStanislas LyonnetKaya BilguvarRichard P LiftonShrikant Manenull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullMark S AndersonBertrand BoissonVivien BéziatShen-Ying ZhangEvangelos AndreakosOlivier HermineAurora PujolPärt PetersonTrine H MogensenLee RowenJames MondStéphanie DebetteXavier de LamballerieCharles BurdetLila BouadmaMarie ZinsPere Soler-PalacinRoger ColobranGuy GorochovXavier SolanichSophie SusenJavier Martínez PicadoDidier RaoultMarc VassePeter K GregersenLorenzo PiemontiCarlos Rodríguez-GallegoLuigi D NotarangeloHelen C SuKai KisandSatoshi OkadaAnne PuelEmmanuelle JouanguyCharles M RicePierre TiberghienQian ZhangJean Laurent CasanovaLaurent AbelAurélie Cobat
Published in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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