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

Journal article

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.

Authors: Marchal, A; Cirulli, ET; Neveux, I; Bellos, E; Thwaites, RS

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: HGG Advances
• Volume: 5
• Issue: 3
• Article number: 100300
• Place of publication: United States
• Publication date: 2024-04-26
• Acceptance date: 2024-04-23
• DOI: 10.1016/j.xhgg.2024.100300
• EISSN: 2666-2477
• Pmid: 38678364
• Language: English
• Keywords: HLA; COVID-19; asymptomatic infection; association; population stratification