Abstract
BackgroundAngiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2. It plays critical roles in both the transmission and the pathogenesis of COVID-19. Comprehensive profiling of ACE2 expression patterns could reveal risk factors of severe COVID-19 illness. While the expression of ACE2 in healthy human tissues has been well characterized, it is not known which diseases and drugs might be associated with ACE2 expression.ResultsWe develop GENEVA (GENe Expression Variance Analysis), a semi-automated framework for exploring massive amounts of RNA-seq datasets. We apply GENEVA to 286,650 publicly available RNA-seq samples to identify any previously studied experimental conditions that could be directly or indirectly associated with ACE2 expression. We identify multiple drugs, genetic perturbations, and diseases that are associated with the expression of ACE2, including cardiomyopathy, HNF1A overexpression, and drug treatments with RAD140 and itraconazole. Our joint analysis of seven datasets confirms ACE2 upregulation in all cardiomyopathy categories. Using electronic health records data from 3936 COVID-19 patients, we demonstrate that patients with pre-existing cardiomyopathy have an increased mortality risk than age-matched patients with other cardiovascular conditions. GENEVA is applicable to any genes of interest and is freely accessible at http://genevatool.org.ConclusionsThis study identifies multiple diseases and drugs that are associated with the expression of ACE2. The effect of these conditions should be carefully studied in COVID-19 patients. In particular, our analysis identifies cardiomyopathy patients as a high-risk group, with increased ACE2 expression in the heart and increased mortality after SARS-COV-2 infection.
Highlights
Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2
(4) ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19, suggesting that the level of ACE2 expression is associated with disease severity [9]
Using GENEVA, we identified multiple drugs, genetic perturbations, and diseases that modulate the expression of ACE2, including cardiomyopathy, HNF1A overexpression, and drug treatments with RAD140 and itraconazole
Summary
Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2 It plays critical roles in both the transmission and the pathogenesis of COVID-19. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2 [2]. (4) ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19, suggesting that the level of ACE2 expression is associated with disease severity [9]. Taking these lines of evidence together, it is crucial to comprehensively characterize the ACE2 expression in human tissues
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