Analysis of Genetics Risk Factors Associated with COVID 19 Severity

Abstract

The COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This complex disease manifests different symptoms across different ethnicities, influenced by both environmental and genetic factors. This study focused on understanding of the genetic risk factors associated withCOVID-19 severity in the Pakistani population. The study was performed on a cohort of 131 individuals categorized into mild (N=53) and severe (N=78) groups. The study examined ACE insertion/deletion polymorphism, a TMPRSS2 variant (rs3787950), and HLA-A*11 genotype in the cohort of 131 individuals. Genotyping was conducted using agarose gel for ACE and HLA-A*11, but Sanger sequencing was performed for TMPRSS2 variant analysis. ACE D/D genotype is more common in individuals within severe group as compared to individuals in the mild group. Statistical analysis, including Fisher's Exact Test (0.04676) and Chi Square test (0.0444) for genotypes, Fisher's Exact Test (0.03153) and Chi Square test (0.03467) for alleles of ACE revealed significant association with severity of COVID-19. To explore the impact of the ACE I allele under recessive and dominant models, further analysis yielded a significant result for recessive effect. This indicates that individuals having I allele are less prone to develop severe disease. TMPRSS2 rs3787950 was the only variant found in our study cohort and the frequency of minor allele is 12%. The HLA-A*11 allele genotyping shows its frequent presence in both severe and mild group. However, no significant associations were found for TMPRSS2 and HLA-A*11 in relation to the disease severity. These findings enhance our understanding of host genetics in the Pakistani population, but additional studies are required to identify additional host genetic factors. Key words: COVID-19, Host genetic Factors, ACE, TMPRSS2, HLA