The study of the origin and spread of SARS-CoV-2 variants that allow escape from presentation by the HLA class I alleles common in human populations.
SARS-CoV-2 evolution is shaped by human adaptive immunity, so that mutations allowing escape from the B-cell response confer selective advantage to the virus and spread in the population. Meanwhile, the role of escape from T-cellular cytotoxic response remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants that allow escape from presentation by the HLA class I alleles common in human populations. We find that 35% of mutations that are characteristic of the variants of concern, and 34% of mutations that have reached high (>5%) frequencies in viral populations, facilitate escape of viral epitopes from presentation by HLA class I alleles. Mutations associated with escape from common HLA alleles reach higher frequencies than those that allow escape from less common HLA alleles, indicating that they are favored by selection. Moreover, viral escape mutations reach higher frequencies in those countries where the causal HLA alleles are more frequent, indicating that escape is driven by the local genetic composition of the human host population. The observed escape cannot be due to selection only in immunosuppressed individuals, and instead indicates selection over the course of acute SARS-CoV-2 infections. Together, these data indicate that CTL escape is a major driver of SARS-CoV-2 evolution and an epidemiological concern, and reveal a novel facet of selection on this virus.