Human Leukocyte Antigen (HLA) Class I Susceptible Alleles Against COVID-19 Increase Both Infection and Severity Rate

Introduction Each country's difference in the severity rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be explained by the difference in human leukocyte antigen (HLA) class I molecules, which affects the reactivity of cytotoxic T lymphocyte (CTL). Methods To clarify the relationship between HLA class I and the severity rate, the binding repertoires of each HLA class I allele to SARS-CoV-2 peptides and the allele frequencies of HLA-A, -B, and -A/B haplotypes in each country were quoted. Results HLA-A1 and the number of deaths per million population (severity rate) in each country had an exponential approximation correlation with correlation coefficient R=0.4879. In addition, the correlation between the infected cases per million (infection rate) and the severity rate was linearly approximated, with R=0.7422. Weak HLA-A alleles with a repertoire of under 300 also had an exponential approximation correlation with the severity rate (R=0.5972), whereas there was a linear approximation with the infection rate (R=0.6808). Weak HLA-B alleles of 30 repertoires or less had no correlation with the severity rate (R=-0.1530). The weak HLA-A/B haplotype has a stronger effect on the severity rate than the weak HLA-A alone. Therefore, the simple HLA class I susceptibility index was calculated, and a strong correlation (R=0.7388) of an exponential approximation with the severity rate was obtained. Conclusions HLA class I susceptible alleles against COVID-19 increase both infection and severity rate. The weak HLA-A is a major factor of severity rate, whereas the weak -B alone has no correlation. However, the weak HLA-A/B haplotype has a stronger effect on the severity rate than the weak -A alone.