Background: Numerous genetic factors influence the severity and susceptibility to COVID-19. The renin-angiotensin system has a role in the genesis of COVID-19. This study aims to investigate the genetic polymorphisms of Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) and ACE2 rs2285666 in patients with COVID-19 and their association with mild, severe, and critical disease symptoms. Materials and Methods: This study included 300 patients with COVID-19, categorized as mild, severe, and critical. Genotypes for the I/D polymorphism of ACE1 and the rs2285666 polymorphism of ACE2 were determined in all samples using polymerase chain reaction (PCR) and restriction fragment length polymorphism-PCR methodologies, respectively. Results: This study revealed a significant association between the ACEI/D genotype and the severity of COVID-19 (p < 0.001). A strong association was seen between the frequency of ACEI/D alleles and the severity of COVID-19, with the D allele being more prevalent in the severe and critical cohorts compared with the mild cohort (p < 0.001). A significant association was found between the ACE2 rs2285666 polymorphism and disease severity in both male and female groups (p < 0.05). The frequency of G/A alleles linked to the ACE2 polymorphism exhibited a significant association with disease severity, as the G allele was more common in the severe and critical groups than in the mild group (p = 0.004). Conclusion: Individuals with the homozygous ACE D/D genotype have an increased susceptibility to severe COVID-19, while the presence of allele I may provide a preventive advantage against severe disease symptoms. The ACE2 rs2285666 variant is associated with disease severity, while the ACE2 G/G genotype is linked to an increased severity of COVID-19.
Keywords: COVID-19; SARS-CoV-2; angiotensin-converting-enzyme; genetic polymorphism.