We found that the presence of HLA-B*08:01 increased the risk of severe COVID-19 by more than eight times and, additionally, the HLA-B*08:01-C*04:01-DRB1*03:01-DQB1*03:01 haplotype was observed in both of our patients with co-presence of four risk alleles. The gene discussed is HLA-B; the disease is COVID-19.