HLA-A homozygosis is associated with susceptibility to COVID-19

HLA. 2021 Aug;98(2):122-131. doi: 10.1111/tan.14349. Epub 2021 Jun 29.

Abstract

The purpose of this single center retrospective study was to investigate the relationship between HLA and ABO polymorphisms and COVID-19 susceptibility and severity in kidney transplant recipients. It included 720 recipients who had COVID-19 and 1680 controls composed by recipients in follow-up who did not contact the transplantation center for COVID-19 symptoms, up to the moment of their inclusion in the study. HLA-A, -B, and -DRB1 allele groups and ABO frequencies were compared between recipients with COVID-19 (all cases, or separately mild/moderate and severe disease) and controls. The HLA association study was conducted in two case-control series and only associations that showed a p-value <0.05 in both series were considered. No HLA association regarding COVID-19 occurrence or severity met this criterion. Homozygosity at HLA-A locus was associated with COVID-19 susceptibility (odds ratio 1.4) but not severity. Blood groups A and O were associated with susceptibility and resistance to COVID-19, respectively. COVID-19 severity was associated only with older age and cardiac disease, in a multivariate analysis. We conclude that an influence of HLA on COVID-19 susceptibility is supported by the association with homozygosity at HLA-A locus but that there is no evidence for a role of any particular HLA-A, -B, or -DRB1 polymorphism. Thus, we suggest that what matters is the overall capability of an individual's HLA molecules to present SARS-CoV-2 peptides to T cells, a factor that might have a great influence on the breadth of the immune response.

Keywords: ABO blood groups; COVID-19; HLA; HLA homozygosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • COVID-19*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-A Antigens / genetics
  • HLA-DRB1 Chains / genetics
  • Humans
  • Retrospective Studies
  • SARS-CoV-2

Substances

  • HLA-A Antigens
  • HLA-DRB1 Chains