Influence of HLA Class I and II Polymorphisms on COVID-19 Severity in a South Brazilian Population.

The high variability of human leukocyte antigen () genes results in each molecule having distinct antigenic peptide binding capacities, potentially influencing the immune response to SARS-CoV-2. This study aimed to investigate associations between (, ) and () polymorphisms and COVID-19 severity in a South Brazilian population, and to evaluate the binding affinity of alleles to viral peptides. A cross-sectional study included 503 unvaccinated patients with RT-qPCR-confirmed COVID-19: 145 non-severe, 129 severe, and 229 critical. typing was performed using PCR-SSO and Luminex™ technology. The allelic group was significantly associated with protection against severe and critical cases, while was associated with increased risk; both remained significant after Bonferroni correction. Other allelic groups were associated with disease outcomes but lost significance after correction: and (risk); and , , and (protection). In silico analysis revealed that the allele group showed a higher proportion of strong binders, mostly from non-structural proteins, while binders, though fewer in number, were concentrated in the M protein. These results suggest functional differences in antigen presentation and reinforce the relevance of , particularly , in modulating COVID-19 severity.