ACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recovery

Abstract During the SARS-CoV-2 pandemic, angiotensin-converting enzyme 2 (ACE2) was identified as the major entry receptor for the virus and transmembrane serine protease 2 (TMPRSS2) as an important SARS-CoV-2 entry factor. Previous studies investigating the impact of ACE2 and TMPRSS2 gene expressio...

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Main Authors: Vanessa Hui En Chen, Joshua K. Tay, Rijan Gurung, Smeetha Nair, Douglas Jie Wen Tay, Kai Sen Tan, Roger S. Y. Foo, Paul A. Tambyah
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-96279-x
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author Vanessa Hui En Chen
Joshua K. Tay
Rijan Gurung
Smeetha Nair
Douglas Jie Wen Tay
Kai Sen Tan
Roger S. Y. Foo
Paul A. Tambyah
author_facet Vanessa Hui En Chen
Joshua K. Tay
Rijan Gurung
Smeetha Nair
Douglas Jie Wen Tay
Kai Sen Tan
Roger S. Y. Foo
Paul A. Tambyah
author_sort Vanessa Hui En Chen
collection DOAJ
description Abstract During the SARS-CoV-2 pandemic, angiotensin-converting enzyme 2 (ACE2) was identified as the major entry receptor for the virus and transmembrane serine protease 2 (TMPRSS2) as an important SARS-CoV-2 entry factor. Previous studies investigating the impact of ACE2 and TMPRSS2 gene expression on SARS-CoV-2 susceptibility in adults have yielded inconsistent results, thereby underscoring the need for further research in this domain. We obtained nasopharyngeal swabs from infected adults during the acute and late convalescent phase of SARS-CoV-2 infection and compared the expression of both genes with non-infected household member contacts. We found that ACE2 and TMPRSS2 gene expression is temporarily reduced during the acute phase of SARS-CoV-2 infection presumably due to viral disruption of transcription. Post-recovery, however, the expression of ACE2 and TMPRSS2 was comparable to non-infected household contacts. The lack of significant differences in ACE2 and TMPRSS2 gene expression between SARS-CoV-2-positive adults and uninfected household controls suggests that factors influencing susceptibility to SARS-CoV-2 infection in adults may extend beyond ACE2 and TMPRSS2 expression. However, the findings should be interpreted with caution due to the study’s limited sample size and the heterogeneity of COVID-19 cases. Other non-physiological factors, such as enhanced hygiene practices following the infection of a household member, may also contribute to absence of infection among healthy controls.
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spelling doaj-art-bc9eb157cf0441729e1d434ed0006e2a2025-08-20T03:18:27ZengNature PortfolioScientific Reports2045-23222025-04-011511610.1038/s41598-025-96279-xACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recoveryVanessa Hui En Chen0Joshua K. Tay1Rijan Gurung2Smeetha Nair3Douglas Jie Wen Tay4Kai Sen Tan5Roger S. Y. Foo6Paul A. Tambyah7Department of Otolaryngology – Head and Neck Surgery, National University of SingaporeDepartment of Otolaryngology – Head and Neck Surgery, National University of SingaporeCardiovascular-Metabolic Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Medicine, National University of SingaporeInfectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of SingaporeInfectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of SingaporeCardiovascular-Metabolic Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Medicine, National University of SingaporeAbstract During the SARS-CoV-2 pandemic, angiotensin-converting enzyme 2 (ACE2) was identified as the major entry receptor for the virus and transmembrane serine protease 2 (TMPRSS2) as an important SARS-CoV-2 entry factor. Previous studies investigating the impact of ACE2 and TMPRSS2 gene expression on SARS-CoV-2 susceptibility in adults have yielded inconsistent results, thereby underscoring the need for further research in this domain. We obtained nasopharyngeal swabs from infected adults during the acute and late convalescent phase of SARS-CoV-2 infection and compared the expression of both genes with non-infected household member contacts. We found that ACE2 and TMPRSS2 gene expression is temporarily reduced during the acute phase of SARS-CoV-2 infection presumably due to viral disruption of transcription. Post-recovery, however, the expression of ACE2 and TMPRSS2 was comparable to non-infected household contacts. The lack of significant differences in ACE2 and TMPRSS2 gene expression between SARS-CoV-2-positive adults and uninfected household controls suggests that factors influencing susceptibility to SARS-CoV-2 infection in adults may extend beyond ACE2 and TMPRSS2 expression. However, the findings should be interpreted with caution due to the study’s limited sample size and the heterogeneity of COVID-19 cases. Other non-physiological factors, such as enhanced hygiene practices following the infection of a household member, may also contribute to absence of infection among healthy controls.https://doi.org/10.1038/s41598-025-96279-xSARS CoV-2ACE2TMPRSS2
spellingShingle Vanessa Hui En Chen
Joshua K. Tay
Rijan Gurung
Smeetha Nair
Douglas Jie Wen Tay
Kai Sen Tan
Roger S. Y. Foo
Paul A. Tambyah
ACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recovery
Scientific Reports
SARS CoV-2
ACE2
TMPRSS2
title ACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recovery
title_full ACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recovery
title_fullStr ACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recovery
title_full_unstemmed ACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recovery
title_short ACE2 and TMPRSS2 gene expression is reduced acutely in SARS-CoV-2 patients but returns to normal with recovery
title_sort ace2 and tmprss2 gene expression is reduced acutely in sars cov 2 patients but returns to normal with recovery
topic SARS CoV-2
ACE2
TMPRSS2
url https://doi.org/10.1038/s41598-025-96279-x
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