Polymorphisms and mutations of ACE2 and TMPRSS2 genes are associated with COVID-19: a systematic review

Abstract

Objective To 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. Introduction 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. 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. Methods Here, 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. Results A 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. Conclusions ACE2 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.

Association of hypernatremia with outcomes of COVID-19 patients: A systematic review and meta-analysis

“…[ 40 ] Many systematic reviews and meta-analysis have delineated ACE2 and TMPRSS2 genes to increase the risk of susceptibility and severity of COVID-19. [ 41 – 43 ] This could lead to tubulopathy or even renal failure, which could explain the loss of free water or sodium retention for hypernatremia.…”

“…[40] Many systematic reviews and meta-analysis have delineated ACE2 and TMPRSS2 genes to increase the risk of susceptibility and severity of COVID-19. [41][42][43] This could lead to tubulopathy or even renal failure, which could explain the loss of free water or sodium retention for hypernatremia. However, ICU patients are at high risk of hypernatremia due to their inability to maintain free water balance due to sedation, intubation and fluid restrictions for various other reasons.…”

The COVID-19 Pandemic and Explaining Outcomes in Africa: Could Genomic Variation Add to the Debate?

“…Polymorphisms that increase TMPRSS2 expression have been reported to increase susceptibility to SARS-CoV-2 infection (Asselta et al, 2020 ; Li et al, 2022 ; Schönfelder et al, 2021 ). In a German case–control study (Schönfelder et al, 2021 ), the frequencies of three variants rs2070788, rs383510, and rs12329760 between cases and controls were investigated.…”

The Prevalence and Impact of Coinfection and Superinfection on the Severity and Outcome of COVID-19 Infection: An Updated Literature Review

“…The common variants of the two proteins most involved in the infection by SARS-CoV-2, namely ACE2 and Tmprss2, have different effects upon the infectiously and severity of COVID-19. Moreover, the factors that modulates these genes such as OM-85, a standardized lysate of bacteria, can be potential treatments [52][53][54] (Table 1). +: increased, −: decreased.…”