Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19

Front Immunol. 2021 Feb 23:12:641900. doi: 10.3389/fimmu.2021.641900. eCollection 2021.

Abstract

Human leukocyte antigen (HLA) class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides at the cell surface where they will be further recognized by T cells. In the present manuscript, we explored whether HLA class I genotypes can be associated with the critical course of Coronavirus Disease-19 by searching possible connections between genotypes of deceased patients and their age at death. HLA-A, HLA-B, and HLA-C genotypes of n = 111 deceased patients with COVID-19 (Moscow, Russia) and n = 428 volunteers were identified with next-generation sequencing. Deceased patients were split into two groups according to age at the time of death: n = 26 adult patients aged below 60 and n = 85 elderly patients over 60. With the use of HLA class I genotypes, we developed a risk score (RS) which was associated with the ability to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides by the HLA class I molecule set of an individual. The resulting RS was significantly higher in the group of deceased adults compared to elderly adults [p = 0.00348, area under the receiver operating characteristic curve (AUC ROC = 0.68)]. In particular, presence of HLA-A*01:01 allele was associated with high risk, while HLA-A*02:01 and HLA-A*03:01 mainly contributed to low risk. The analysis of patients with homozygosity strongly highlighted these results: homozygosity by HLA-A*01:01 accompanied early deaths, while only one HLA-A*02:01 homozygote died before 60 years of age. Application of the constructed RS model to an independent Spanish patients cohort (n = 45) revealed that the score was also associated with the severity of the disease. The obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19.

Keywords: COVID-19; HLA class I; MHC class I; SARS-CoV-2; peptide presentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alleles
  • COVID-19 / immunology*
  • COVID-19 / mortality*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Testing / methods
  • Genotype*
  • HLA-A Antigens / genetics*
  • High-Throughput Nucleotide Sequencing / methods
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • SARS-CoV-2 / genetics*
  • Severity of Illness Index*

Substances

  • HLA-A Antigens