Abstract 12017: The Prognostic Role of Genotypic Variants of ACE2 and TMPRSS2 Polymorphisms in SARS-CoV2 / COVID-19 Infection

Abstract

BACKGROUND: the entry of the SARS-CoV-2 into cells is mediated by the binding between the virus Spike-glycoprotein and the membrane ACE2-receptor (ACE2-R). When SARS-CoV-2 binds to ACE2-R, a down-regulation of these receptors occurs, playing a crucial role in the inflammatory response. A dysregulation of the RAAS linked to a different expression of ACE2-R and TMPRSS2 gene polymorphisms and different levels of serum ACE2 (sACE2), could be associated with abnormal inflammatory and immune response to SARS-CoV-2 infection. AIM OF THE STUDY: we aimed to verify whether there is an association between the clinical course of COVID-19 pts and the presence of more frequent ACE2 and TMPRSS2 single-nucleotide polymorphisms (SNPs) and if sACE2 levels are related to specific ACE2 and TMPRSS2 polymorphic variants. Methods: we consecutively enrolled subjects with previous documented SARS-CoV-2 infection and divided our sample into three groups: pts with asymptomatic course; pts with symptomatic course without an hospitalization for COVID-19; pts with severe symptomatic course requiring hospitalization in ICU. Data about age, clinical course, comorbidities, and therapies were collected. Blood samples were taken for the genetic analysis of the most frequent SNPs of the ACE2-R and TMPRSS2 detected in Italian population, in particular genotypic variants TT and CC of ACE2 SNPs 1 and 5 (5% and 14% respectively) and genotypic variants TT and CC of TMPRSS2 SNPs 2 and 3 (rate of 50% and 30% respective). Results: among 178 pts enrolled up to March 2022, we have so far analyzed the genetic polymorphisms of 74 pts; 21 (28%) were hospitalized for COVID-19, 38 (51%) had symptomatic course without hospitalization and 15 (21%) were completely asymptomatics. We found that sACE2 levels were higher in genotypic variant CC of SNP 1 of TMPRSS2 gene. Considering that a high concentration of sACE2 outlines a proinflammatory condition, it could be hypothesized that the CC genotype may be a predisposing condition to the cytokine storm of COVID-19. PERSPECTIVES: Genetic analysis of ACE2 and TMPRSS2 SNPs will help to clarify the relationship between these polymorphic variant, sACE2 levels, risk of SARS-CoV2 infection and severity of clinical presentation of COVID-19 in pts with or without CV diseases.