Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Marchal, Astrid; COVID Clinicians; Bolze, Alexandre

doi:http://dx.doi.org/10.1016/j.xhgg.2024.100300

Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

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Marchal A, Cirulli ET, Neveux I, Bellos E, Thwaites RS, Schiabor Barrett KM, et al. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection. HGG Adv. 2024 Apr 26;5(3):100300. DOI: 10.1016/j.xhgg.2024.100300

Abstract

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 COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.