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

## TL;DR

This study explores how variations in HLA genes affect the severity of COVID-19 in a Brazilian population, finding that certain HLA alleles are linked to either protection or increased risk.

## Contribution

The study identifies specific HLA class II alleles associated with protection or risk for severe/critical COVID-19 outcomes in a South Brazilian population.

## Key findings

- The DRB1*11 allelic group is associated with protection against severe and critical COVID-19.
- The DRB1*15 allelic group is associated with increased risk of severe and critical disease.
- In silico analysis shows DRB1*15 has higher binding affinity to SARS-CoV-2 non-structural proteins.

## Abstract

The high variability of human leukocyte antigen (HLA) 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 HLA class I (A, B) and class II (DRB1) 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. HLA typing was performed using PCR-SSO and Luminex™ technology. The DRB1*11 allelic group was significantly associated with protection against severe and critical cases, while DRB1*15 was associated with increased risk; both remained significant after Bonferroni correction. Other allelic groups were associated with disease outcomes but lost significance after correction: B*49 and B*08 (risk); and B*37, B*50, and A*03 (protection). In silico analysis revealed that the DRB1*15 allele group showed a higher proportion of strong binders, mostly from non-structural proteins, while DRB1*11:01 binders, though fewer in number, were concentrated in the M protein. These results suggest functional differences in antigen presentation and reinforce the relevance of class II HLA, particularly DRB1, in modulating COVID-19 severity.