Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study

Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality.

We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from 'Worldometer'. Multivariable analyses were also undertaken adjusting for age (median age), sex (percentage of females) and the number of COVID-19 tests undertaken. Associations between genotypes deletion/deletion (DD) and insertion/insertion (II) prevalence and COVID-19-related mortality (per million people per day since the first diagnosed case) were evaluated.

The frequency of II genotype is highest in east Asian countries and lower among the European and African countries. An inverse geographical distribution frequency was noted for DD genotype. Increasing II genotype frequency was significantly associated with decreased COVID-19 mortality rates (adjusted incident rate ratio [IRR] 0.3, 95% confidence interval [CI]: 0.002-0.7, p = 0.03). However, no association was found between DD genotype frequency and COVID-19 mortality rates (adjusted IRR 4.3, 95% CI: 0.5-41.2, p = 0.2).

Distribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality. This information has potential utility for resource planning at a systemic level, as well as for clinical management.