Pan-cancer analysis of RNA expression of ANGIOTENSIN-CONVERTING ENZYME II (ACE2) and cellular proteases reveals high variability and possible impact on COVID-19 clinical outcomes

Abstract Patients with cancer demonstrate particularly poor outcomes from COVID-19. To provide information essential for understanding the biologic underpinnings of this association, we analyzed whole-transcriptome RNA expression data obtained from a large cohort of cancer patients to characterize expression of ACE2, TMPRSS2, and other proteases that are involved in viral attachment to and entry into target cells. We find substantial variability of expression of these factors across tumor types and identify subpopulations expressing ACE2 at very high levels. In some tumor types, especially in gastrointestinal cancers, expression of ACE2 and TMPRSS2 is highly correlated. Furthermore, we found infiltration with T-cell and natural killer (NK) cell infiltration to be particularly pronounced in ACE2-high tumors. These findings suggest that subsets of cancer patients exist with heightened susceptibility to SARS-CoV-2 infection in whom malignant tumors function as viral reservoir and possibly promote the frequently detrimental hyper-immune response in patients infected with this virus.