HLA Genetic Variants in COVID-19 Susceptibility: Assessing Diversity in Indian and Global Populations

Background: The rapid spread of the SARS-CoV-2 virus has had a global impact on various ethnic groups. In order to assess the genetic predisposition of the Indian population towards COVID-19, a comparative analysis was conducted using the Human Leukocyte Antigen (HLA) to investigate the frequencies of polymorphisms directly or potentially associated with COVID-19 susceptibility, severity, immune response, and fatal outcomes in comparison to other major populations. Objectives: The objective of this study is to evaluate the genetic predisposition of the Indian population to COVID-19 by analyzing the frequencies and associations of Human Leukocyte Antigen (HLA) polymorphisms. In addition, by delineating the role of specific HLA variants in the Indian context, the study seeks to enhance our understanding of genetic factors influencing COVID-19 impact and contribute to personalized approaches for disease management and prevention across diverse ethnic groups. Methods: We collected allelic information for DRB1 gene from 653 populations globally, as documented in The Allele Frequency Net Database (AFND). Data on COVID-19 susceptibility, severity, mortality, and protective factors were obtained from a previous global study. This study aimed to compare the specific frequencies of HLA-DRB1* in different ethnic groups, including other Indian populations with COVID-19-associated alleles and protective factors. Results: HLA-DRB1*01 was identified as a significant determinant of COVID-19 susceptibility among patients in 28 states of Mexico, whereas DRB1*08 in Saudi Arabian populations, DRB1*09:01 in Japanese populations, and DRB1*15:01 in Italian populations also showed this association. Likewise, DRB1*04 in the Iranian population played a role in disease severity, and DRB1*08 in the Italian population was associated with mortality in COVID-19 patients. In addition, alleles DRB1*01:01 and DRB1*04:01 were found to exhibit a protective role in Northeast England, whereas DRB1*04 demonstrated protective effects in Saudi Arabian populations. Conclusion: The involvement of HLA in COVID-19 requires further investigation, and epidemiological studies should focus on HLA profiles as determinants of the host immune system. Prolonged homozygosity in particular genomic regions could potentially increase susceptibility to COVID-19 infection. Therefore, prudent management strategies are recommended for this pandemic in isolated communities in India and worldwide.