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Updated: Oct 5, 2025

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
A common TMPRSS2 variant has a protective effect against severe COVID-19
Alessia David1, Nicholas Parkinson2, Thomas P Peacock3
1Centre for Integrative System Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
A common genetic variant in the transmembrane protease serine type 2 (TMPRSS2) gene, rs12329760, is linked to a lower risk of severe COVID-19. This TMPRSS2 variant impairs SARS-CoV-2 entry into cells, suggesting it as a potential drug target.
Area of Science:
- Genetics
- Virology
- Molecular Biology
Background:
- Transmembrane protease serine type 2 (TMPRSS2) is crucial for SARS-CoV-2 entry by activating the viral spike protein.
- Naturally occurring genetic variants in TMPRSS2 may influence SARS-CoV-2 infection severity.
Purpose of the Study:
- To investigate the association between a common TMPRSS2 genetic variant (rs12329760 C>T, p.V160M) and COVID-19 severity.
- To determine the in vitro functional impact of the TMPRSS2 V160M variant on viral entry.
Main Methods:
- Analysis of rs12329760 association with COVID-19 severity in 2,244 critically ill patients.
- Logistic regression adjusted for clinical covariates.
- In vitro studies using HEK293 cells to assess TMPRSS2 V160M function in SARS-CoV-2 pseudovirus entry assays.
Main Results:
- The T allele of rs12329760 was associated with a reduced risk of severe COVID-19 (OR 0.87, p=0.01), with a stronger effect in homozygous individuals (OR 0.65, p=1.3x10^-3).
- In vitro, the TMPRSS2 V160M variant showed reduced catalytic activity and impaired SARS-CoV-2 spike-mediated viral entry.
Conclusions:
- The common TMPRSS2 rs12329760 variant is associated with decreased risk of severe COVID-19.
- TMPRSS2 is a potential drug target for COVID-19, with camostat mesilate as a possible therapeutic agent.
- Further clinical trials are warranted to confirm these findings and explore therapeutic potential.
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