Association between HLA gene polymorphisms and mortality of COVID‐19: An in silico analysis

Abstract

Introduction The emergence of SARS‐CoV‐2 has caused global public health and economic crisis. Human leukocyte antigen (HLA) is a critical component of the viral antigen presentation pathway and plays essential roles in conferring differential viral susceptibility and severity of diseases. However, the association between HLA gene polymorphisms and risk for COVID‐19 has not been fully elucidated. We hypothesized that HLA genotypes might impact on the differences in morbidity and mortality of COVID‐19 across countries. Methods We conducted in silico analyses and examined an association of HLA gene polymorphisms with prevalence and mortality of COVID‐19 by using publicly available databases. Results We found that a possible association between HLA‐A*02:01 and an increased risk for COVID‐19. HLA‐A*02:01 had a relatively lower capacity to present SARS‐CoV‐2 antigens compared with other frequent HLA class I molecules, HLA‐A*11:01 or HLA‐A*24:02. Conclusion This study suggests that individuals with HLA‐A*11:01 or HLA‐A*24:02 genotypes may generate efficiently T‐cell‐mediated antiviral responses to SARS‐CoV‐2 compared with HLA‐A*02:01. The differences in HLA genotypes may potentially alter the course of the disease and its transmission.

The Role of Immunogenetics in COVID-19

“…Curiously, in countries where HLA-A*02:01 is the most frequent in the population, a significant correlation exists with mortality (expressed as deaths out of 10 6 population) vs. countries where HLA-A*24:02 or HLA-A*11:01 are the most frequent alleles, as confirmed at two different time points (April 2020 p = 0.003 and August 2020 p < 0.001, respectively), excluding from further analysis that the number of recorded deaths accounts for the simple increase in COVID-19 cases regardless of the HLA genotype. The authors also predicted the functional performance of the three analyzed alleles, with HLA-A*02:01 having the lowest viral antigen-presenting capacity in comparison with HLA-A*24:02 and HLA-A*11:01, completely contradicting a previous paper reporting that the number of loosely+tightly binding peptides was higher for HLA-A*02:01 vs. both HLA-A*11:01 and HLA-A*24:02 [ 51 , 53 , 54 ].…”

“…Furthermore, serotype HLA-B22 was found more frequently in COVID-19 Hong Kong Chinese patients vs. non-age matched controls but the association was not significant when the comparison was made against age matched controls [ 46 ]. Finally, it was demonstrated that countries where HLA-A*02:01 is the most frequent in the population had lower numbers of COVID-19 cases out of 10 6 population vs. countries where HLA-A*24:02 or HLA-A*11:01 are the most frequent alleles, as confirmed at two different time points (April 2020 p = 0.009 and August 2020 p = 0.013) [ 53 ].…”

MHC Haplotyping of SARS-CoV-2 patients: HLA subtypes are not associated with the presence and severity of Covid-19 in the Israeli population

“…Similarly, an association between severe disease outcome and speci c HLAs was suggested by another small-scale whole-genome sequencing study 29 . In silico model raised the possibility that HLA supertypes may have a role in the severity of the disease 30 .…”

Hypothetical COVID-19 protection mechanism: hints from centenarians

“…However, it has been demonstrated that SARS-CoV-2 derived peptides processed in human cells, are presented by HLA class I molecules inducing SARS-CoV-2 specific cytotoxic innate immune response [ 35 ]. The different alleles of the HLA genes show different affinity to bind virus derived peptides, maybe causing a different risk to develop COVID-19 [ 35 ].…”