HLA-A*11:01 and HLA-C*04:01 are associated with severe COVID-19.

We analyzed the association between HLA polymorphisms and susceptibility to SARS-CoV-2 infection and disease severity. Genotyping data from a total of 9373 COVID-19-positive cases from the Spanish Coalition to Unlock Research on Host Genetics on COVID-19 (SCOURGE) consortium and 5943 population controls were included in the study. We found an association of the alleles HLA-B*14:02 and HLA-C*08:02 with a lower risk to COVID-19 infection (p = 0.006, OR = 0.84, 95% CI = [0.75-0.95], p = 0.024, OR = 0.86, 95% CI = [0.78-0.95], respectively). We also found the alleles HLA-A*11:01 and HLA-C*04:01 associated with disease severity (p = 0.033, OR = 1.16, 95% CI = [1.04-1.31], p = 0.045, OR = 1.14, 95% CI = [1.05-1.25], respectively). These results suggest that an effective presentation of viral peptides by HLA class I alleles involve a faster infection clearance, decreasing the susceptibility and severity of COVID-19.