A meta-analysis of the association of the ACE I/D variant and COVID-19 susceptibility and severity

Background: Several studies investigated the association of ACE I/D polymorphism with the risk and severity of COVID-19 infection.  However, the information in each of the published studies is limited, and the results were inconsistent or even contradictory. Accordingly, this meta-analysis evaluated the association between the ACE I/D polymorphism and COVID-19 susceptibility and severity. Methods: Two investigators independently searched the PubMed, Embase, Google Scholar, Scopus and Science Direct databases. Five studies including 1029 cases and 3561 controls were retrieved to evaluate the association of the ACE I/D polymorphism and the risk of COVID-19. Furthermore, meta-analysis of the correlation between ACE I/D variant and the severity of infection covered 5 case-control studies, including 264 sever-cases and 447 mild-cases. Results: Four genetic models including allele contrast (I vs. D), recessive (II vs. ID and DD), dominant (II+ID vs. DD) and over-dominant (ID vs. II+DD) were used to compare the genotypes and alleles. Our analysis indicated that there was no association between ACE I/D variant in all genetic models and COVID-19 susceptibility. However, our analysis revealed that there was a significant association between ACE I/D variant in the allele contrast (95% CI = 0.5291-0.8353; P<0.001), recessive (95% CI = 0.4268- 0.9172; P=0.01) and dominant (95% CI = 0.3974-0.8092; P=0.001) models and severity of COVID-19. Conclusion: This study revealed that the ACE I/D polymorphism is significantly associated with the severity COVID-19 infection. However, further study is still required to confirm the association in different populations.