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

Identifier:  imarina:9411017

Handle: https://hdl.handle.net/20.500.11797/imarina9411017

Authors:  Marchal, Astrid; Cirulli, Elizabeth T; Neveux, Iva; Bellos, Evangelos; Thwaites, Ryan S; Barrett, Kelly M Schiabor; Zhang, Yu; Nemes-Bokun, Ivana; Kalinova, Mariya; Catchpole, Andrew; Tangye, Stuart G; Spaan, Andras N; Lack, Justin B; Ghosn, Jade; Burdet, Charles; Gorochov, Guy; Tubach, Florence; Hausfater, Pierre; Dalgard, Clifton L; Fellay, Jacques; Grzymski, Joseph J; Sancho-Shimizu, Vanessa; Casanova, Jean-Laurent; Cobat, Aurelie; Bolze, Alexandre

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.