Comorbidities such as diabetes, chronic lung disease, and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and associated with worse outcomes. However, whether these conditions contribute directly to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virulence or simply worsen outcomes through independent mechanisms and reflect the general disease burden of the population remain unclear. As an important aspect of virulence, viral entry mechanisms have been proposed which require host cell membrane-bound angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2). Herein, we survey expression data of SARS-CoV-2 entry-related genes from 69 differential expression datasets from patients suffering from a variety of reported common comorbidities and across infection-relevant organ systems to understand their potential role in morbidity and mortality of COVID-19. Indeed, expression levels of entry-related genes are modulated by the disease state of the organ systems analyzed. Expression levels were lower in some comparisons such as type 2 diabetes in whole blood and peripheral blood mononuclear cells (PBMCs). However, many of these genes were consistently upregulated in cancer, a history of smoking, asthma in bronchial epithelium and chronic lung disease in pulmonary tissues. Additionally, increased expression was found in select sets of hypertension, type 1 diabetes, cardiomyopathy and chronic kidney disease (CKD) in other infection-relevant tissues. These findings may be particularly relevant to the significant morbidity and mortality seen in COVID-19 and may suggest novel therapeutic targets to influence outcomes in patients infected with SARS-CoV-2.
Impact of Comorbidities on the Expression of SARS-CoV-2 Viral Entry-Related Genes