Angiotensin-Converting Enzyme 2 (Ace2) and the Transmembrane Protease Serine 2 (Tmprss2): Biomarkers for Predicting Covid-19 Disease Severity Publisher



Farzanegan B ; Bahrami N ; Akhtari M ; Fathi M ; Tahmasebi S ; Pour Dizaji MK ; Shafaghi S ; Hajimoradi M ; Mohamadnia A
Source: Molecular Genetics, Microbiology and Virology Published:2025

Abstract

The angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane protease serine 2 (TMPRSS2) play pivotal roles in the infection of SARS-CoV-2. Therefore, their expression patterns are paramount in understanding the disease’s pathophysiology. Here, we investigated the gene expression of TMPRSS2 and ACE2 in the peripheral blood of severe and mild COVID-19 patients compared to affected individuals who have recovered. The study included 40 patients with severe infection, 40 with mild disease, and 40 age and sex-matched individuals who had recovered from COVID-19 infection. Peripheral blood from the patients was isolated, and the mRNA expression levels of ACE2 and TMPRSS2 were investigated by quantitative PCR. The positivity rate of ACE2 and TMPRSS2 exhibited a significant increasing and reducing trend with decreasing disease severity, respectively (P < 0.001 for both). The expression of ACE2 showed a 2.32-fold and 2.17-fold reduction in the severe and mild infection groups, respectively, compared to the recovered group. The expression of TMPRSS2 was 2.78 times and 2.49 times elevated in patients with severe and mild infection, respectively, than in recovered individuals. In the biomarker analysis, the region under the Receiver Operating Characteristic Curve (AUC-ROC) for ACE2 and TMPRSS2 were 0.85 and 0.61 respectively (P < 0.05). This supports the notion that dysregulation of ACE2 and TMPRSS22 expression may contribute to disease severity and progression in COVID-19. ACE2 and TMPRSS2 could serve as effective biomarkers for predicting infection severity in affected individuals. © 2025 Elsevier B.V., All rights reserved.