Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, CA 92093, USA
Research Service, VA San Diego Healthcare System San Diego, La Jolla, CA 92161, USA
Department of Urology, VA San Diego Healthcare System, University of California San Diego, La Jolla, CA 92093, USA
Urology Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Department of Radiology, Radiology Service, VA San Diego Healthcare System San Diego, University of California San Diego, La Jolla, CA 92093, USA
Radiology Service, VA San Diego Healthcare System San Diego, La Jolla, CA 92161, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(10), 3627; https://doi.org/10.3390/ijms21103627
Received: 28 April 2020 / Revised: 13 May 2020 / Accepted: 17 May 2020 / Published: 21 May 2020
(This article belongs to the Collection Feature Papers in Molecular Oncology)
The COVID-19 pandemic is marked by a wide range of clinical disease courses, ranging from asymptomatic to deadly. There have been many studies seeking to explore the correlations between COVID-19 clinical outcomes and various clinical variables, including age, sex, race, underlying medical problems, and social habits. In particular, the relationship between smoking and COVID-19 outcome is controversial, with multiple conflicting reports in the current literature. In this study, we aim to analyze how smoking may affect the SARS-CoV-2 infection rate. We analyzed sequencing data from lung and oral epithelial samples obtained from The Cancer Genome Atlas (TCGA). We found that the receptor and transmembrane protease necessary for SARS-CoV-2 entry into host cells, ACE2 and TMPRSS2, respectively, were upregulated in smoking samples from both lung and oral epithelial tissue. We then explored the mechanistic hypothesis that smoking may upregulate ACE2 expression through the upregulation of the androgen pathway. ACE2 and TMPRSS2 upregulation were both correlated to androgen pathway enrichment and the specific upregulation of central pathway regulatory genes. These data provide a potential model for the increased susceptibility of smoking patients to COVID-19 and encourage further exploration into the androgen and tobacco upregulation of ACE2 to understand the potential clinical ramifications.