Abstract
ObjectiveTo determine the effect of polymorphisms and mutations in angiotensin-converting enzyme 2 (ACE2) and Type 2 transmembrane serine proteases (TMPRSS2) genes on susceptibility to corona virus disease 2019 (COVID-19) and patient prognosis.IntroductionFrom December 2019 to the current time, an outbreak of epidemic of COVID-19, characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred around the world. It is now clear that SARS-CoV-2 binds to human ACE2 receptors, with expression of these receptors correlated with the rate of SARS-CoV-2 infection and mortality. Polymorphisms in individual patient factors, such as ACE2 and TMPRSS2 genes have been linked with an increase in negative outcomes, although evidence to affirm remains debatable.MethodsHere, we performed a systematic review, based on guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, with the aim of assessing whether polymorphisms in ACE2 and TMPRSS2 genes affect the COVID-19 condition. We extensively searched PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science databases, for relevant articles and reports published in English between December 2019 and December 2021.ResultsA total of 495 full-text articles were downloaded, of which 185 were excluded after preliminary examination as they were duplicates. Finally, 310 articles were evaluated, by reading their titles and abstracts, and 208 of them eliminated based on our selection criteria. Finally, 33 articles met our inclusion criteria and were included in the final assessment. Genetic data from 33,923 patients with COVID-19 drawn from the general population and deriving from over 160 regions and 50 countries, as well as approximately 560,000 samples from global-public genetic databases, were included in our analysis. Ultimately, we identified 10 SNPs and 21 mutations in the ACE2 gene, along with 13 SNPs and 12 variants in the TMPRSS2 gene, which may be associated with COVID-19.ConclusionsACE2 and TMPRSS2 play vital roles in the onset, development, and prognosis of SARS-CoV-2 infection, and have both been strongly associated with vulnerability, intensity, and the clinical result of COVID-19. Overall, these genetic factors may have potential for future development of personalized drugs and vaccines against COVID-19.Trial registration: CRD42021239400 in PROSPERO 2021.
Highlights
From December 2019 to the current time, an outbreak of epidemic of COVID-19, characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred around the world
Genetic data from 33,923 patients with COVID-19 drawn from the general population and deriving from over 160 regions and 50 countries, as well as approximately 560,000 samples from global-public genetic databases, were included in our analysis
We identified 10 single nucleotide polymorphisms (SNPs) and 21 mutations in the angiotensin-converting enzyme 2 (ACE2) gene, along with 13 SNPs and 12 variants in the TMPRSS2 gene, which may be associated with COVID-19
Summary
From December 2019 to the current time, an outbreak of epidemic of COVID-19, characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred around the world. Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), which was first discovered in December 2019 as a new human pathogen, has subsequently become a global. Previous studies have demonstrated that manifestations and the course of COVID-19 disease are associated with an individual’s age, race, ethnic origin, sex, angiotensin-converting enzyme 2 (ACE2) expression pattern, and immunological modulation [8]. Researchers supporting the use of these drugs argue that ACE2 functional blockers may inhibit cellular entry of SARSCoV-2 virus and improve patient prognosis. The opposing camp holds that continued use of these agents leads to high expression of ACE2 receptors in the respiratory epithelium, facilitating entry of SARS-CoV-2 into cells, which leads to enhanced viral replication and accompanying tissue damage [9, 10]. Epidemiological and genome-wide association studies have associated genetic variability to individual variations in sensitivity to COVID-19 [11]
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