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

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.