Antigen Coverage Presented by MHC Class I Has a Negative Correlation with SARS-CoV-2-Induced Mortality

The COVID-19 pandemic has caused a health crisis worldwide; therefore, it is necessary to understand the factors related to its prognosis. In this study, we hypothesized that SARS-CoV-2-derived antigens presented by MHC class I may correlate with mortality in COVID-19 because they induce adaptive immune responses. Antigen coverage at the national level was inferred using country-specific HLA allele frequencies and relative predictions of binding antigens. We performed regression analysis between antigen coverage and the death rate due to COVID-19 across countries and found a negative correlation, although it was statistically significant only in HLA-B. This negative correlation was corroborated in multiple regression analysis with known risk factors, such as the prevalence of underlying disease. Furthermore, we analyzed antigen coverage in accordance with SARS-CoV-2 domains and identified a significant negative correlation when it was derived from the spike domain, which is reported to be favorable for COVID-19 prognosis. Taken together, the results indicate that the antigen coverage of SARS-CoV-2 specifically presented by HLA-B may act as a favorable factor when explaining COVID-19-induced mortality.