Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients

Background: Coronaviruses (CoV) are a large family of viruses that are common in humans and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East respiratory syndrome (MERS-CoV), the severe acute respiratory syndrome corona virus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Several studies suggested that genetic variants in theACE2gene may influence the host susceptibility or resistance to SARS-CoV-2 infection according to the functional role of ACE2 in human pathophysiology. However, many of these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence ofACE2variants in a cohort of 131 Italian unrelated individuals clinically diagnosed with COVID-19 and in an Italian control population, to evaluate a possible allelic association with COVID-19, by direct DNA analysis. Methods: As a pilot study, we analyzed, by whole-exome sequencing, genetic variants ofACE2gene in 131 DNA samples of COVID-19 patients hospitalized at Tor Vergata University Hospital and at Bambino Gesu Children's Hospital, Rome. We used a large control group consisting of 1000 individuals (500 males and 500 females). Results: We identified three different germline variants: one intronic c.439+4G>A and two missense c.1888G>C p.(Asp630His) and c.2158A>G p.(Asn720Asp) in a total of 131 patients with a similar frequency in male and female. Thus far, only the c.1888G>C p.(Asp630His) variant shows a statistically different frequency compared to the ethnically matched populations. Therefore, further studies are needed in larger cohorts, since it was found only in one heterozygous COVID-19 patient. Conclusions: Our results suggest that there is no strong evidence, in our cohort, of consistent association ofACE2variants with COVID-19 severity. We might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of theACE2gene, known to play a role in regulation of the gene activity.