Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection.
Marchal A., Cirulli ET., Neveux I., Bellos E., Thwaites RS., Schiabor Barrett KM., Zhang Y., Nemes-Bokun I., Kalinova M., Catchpole A., Tangye SG., Spaan AN., Lack JB., Ghosn J., Burdet C., Gorochov G., Tubach F., Hausfater P., COVID Human Genetic Effort None., COVIDeF Study Group None., French COVID Cohort Study Group None., CoV-Contact Cohort None., COVID-STORM Clinicians None., COVID Clinicians None., Orchestra Working Group None., Amsterdam UMC COVID-19 Biobank None., NIAID-USUHS COVID Study Group None., Dalgard CL., Zhang S-Y., Zhang Q., Chiu C., Fellay J., Grzymski JJ., Sancho-Shimizu V., Abel L., Casanova J-L., Cobat A., Bolze A.
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.