biostudies-literatureMarchal ANCATS NIH HHSNIAID NIH HHSNIH100300https://www.ebi.ac.uk/biostudies/studies/S-EPMC11215417biostudies-literatureUnknown5(3)Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVHGG advancesLack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection.PMC11215417R01 AI163029UL1 TR001866Foti GSancho-Shimizu VLaverdant BArquero MFvan der Poll TCOVIDeF Study GroupAccordino GCollet MCarrabba MHraiech SWouters DEtxart Lasa MPGagro ABenkhelouf ABulle EDerridj NKlocperk AFuret TRodriguez-Gallego CBlanche PHorn JSaks KArlet JBHorcajada JPTaupin JLSukumar GVught LARedin CSpaan ANPape JWCordel HManivet PGhezal MDesguerre IGibelin ALacombe KSchluter AStepanovskiy YAudiffred LCiterio GTheodose IArzoine JBerard LDrouet EJimeno MTSacleux SCLaine FCao ABouziri NVedie BTipu IMeyts IHeath JRUddin MJZuber JKouakam CColobran RBaronnet FSchrauwen FAPMarseglia GLSavale LHeppekcan DBonnet NBouchaud OAwotar CMontagne SRebillat ASvan Vugt MGautier MMunoz-Barrera AHalwani RKetz FAgostini HAngoulvant FMarchal AMogensen 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RNicolas LNarvaez RUVaittinadaayar PGeromin DIkherbane GOmar EMergeay-Fabre MDe Castro NGonzales NPoissy JPourcelot ANguyen CDe Rycke YNguyen DLim EHTDeschamps LOkada SHanitsch LGfalseLack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection.Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COV2024-01-01T00:00:00Z2024 Jul2026-05-29T10:04:34.678Z2025-04-07T02:07:28.793ZS-EPMC112154173867836410.1016/j.xhgg.2024.100300