RT Journal Article
SR Electronic
T1 Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.26.117440
DO 10.1101/2020.05.26.117440
A1 Joshua D. Breidenbach
A1 Prabhatchandra Dube
A1 Subhanwita Ghosh
A1 Nikolai N. Modyanov
A1 Deepak Malhotra
A1 Lance D. Dworkin
A1 Steven T. Haller
A1 David J. Kennedy
YR 2020
UL http://biorxiv.org/content/early/2020/06/04/2020.05.26.117440.abstract
AB Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2). The distribution of expression of these genes across cell types representing multiple organ systems in healthy individuals has been recently demonstrated. However, comorbidities such as diabetes and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and associated with worse outcomes. Whether these conditions contribute directly to SARS-CoV-2 virulence remain unclear. Here we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes are modulated in target organs of select disease states. In tissues such as heart, which normally express ACE2 but minimal TMPRSS2, we found that TMPRSS2 as well as other TTSPs are elevated in individuals with comorbidities vs healthy individuals. Additionally, we found increased expression of viral entry-related genes in the settings of hypertension, cancer or smoking across target organ systems. Our results demonstrate that common comorbidities may contribute directly to SARS-CoV-2 virulence and suggest new therapeutic targets to improve outcomes in vulnerable patient populations.Competing Interest StatementThe authors have declared no competing interest.