Association of ACE2 Gene Variants with the Severity of COVID-19 Disease-A Prospective Observational Study

Int J Environ Res Public Health. 2022 Oct 2;19(19):12622. doi: 10.3390/ijerph191912622.


The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), has triggered an enormous scientific response. Many studies have focused on understanding the entry of the SARS-CoV-2 virus into the host cell. The angiotensin-converting enzyme-2 (ACE2) is recognized as the host receptor used by SARS-CoV-2 to enter its target cells. Recent studies suggest that ACE2 gene polymorphisms might be candidates for genetic susceptibility to SARS-CoV-2 infection. The aim of this study is to evaluate the influence of ACE2 polymorphisms on COVID-19 disease risk and severity. In our study, we confirmed that there is a statistically significant increased risk of a more severe disease course of SARS-CoV-2 infection associated with the need for hospitalization in intensive care for patients with specific polymorphisms of the ACE2 gene. The most significant correlation was found for variant ACE2 rs2285666 (AA allele, OR = 2.12, p = 0.0189) and ACE2 rs2074192 (TT allele, OR = 2.05, p = 0.0016), and for ACE2 rs4646174 (GG allele, OR = 1.93, p = 0.0016), ACE2 rs4646156 (TT allele OR = 1.71, p = 0.008) and ACE2 rs2158083 (TT allele OR = 1.84, p = 0.0025). In conclusion, our findings identify that certain ACE2 polymorphisms impact the severity of COVID-19 disease independently of other well-known risk factors.

Keywords: SARS-CoV-2; angiotensin receptors; coronavirus; gene polymorphism; single nucleotide polymorphism.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics*
  • Angiotensins / genetics
  • COVID-19* / epidemiology
  • COVID-19* / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • SARS-CoV-2 / genetics


  • Angiotensins
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grant support

This research was funded by the Polish Medical Research Agency (ABM), grant number 2020/ABM/COVID19/0023.