ACE I/D polymorphism in Czech first-wave SARS-CoV-2-positive survivors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread from China in 2019/2020 to all continents. Significant geographical and ethnic differences were described, and host genetic background seems to be important for the resistance to and mortality of COVID-19. Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4646994) is one of the candidates with the potential to affect infection symptoms and mortality.

In our study, we successfully genotyped 408 SARS-CoV-2-positive COVID-19 survivors (163 asymptomatic and 245 symptomatic) and compared them with a population-based DNA bank of 2,559 subjects.

The frequency of ACE I/I homozygotes was significantly increased in COVID-19 patients compared with that in controls (26.2% vs. 21.2%; P = 0.02; OR [95% CI] = 1.55 [1.17-2.05]. Importantly, however, the difference was driven just by the symptomatic subjects (29.0% vs. 21.2% of the I/I homozygotes; P = 0.002; OR [95% CI] = 1.78 [1.22-2.60]). The genotype distribution of the ACE genotypes was almost identical in population controls and asymptomatic SARS-CoV-2-positive patients (P = 0.76).

We conclude that ACE I/D polymorphism could have the potential to predict the severity of COVID-19, with I/I homozygotes being at increased risk of symptomatic COVID-19.