Human cardiac pericytes are susceptible to SARS-CoV-2 infection

Coronavirus disease 2019 (COVID-19) is associated with serious cardiovascular complications, including myocarditis, thrombosis, and dysregulated hemodynamic responses. The mechanism(s) underlying these disease manifestations are incompletely understood. Given a critical role for pericytes in supporting endothelial cell health and maintaining vascular integrity, we hypothesized that infection of pericytes could explain some of the cardiovascular complications of COVID-19. Here, we present evidence of SARS-CoV-2 infection in cardiac pericytes in patients with COVID-19 myocarditis. We show that cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. SARS-CoV-2 enters cardiac pericytes through an ACE2 and endosomal-dependent mechanism. Consequences of cardiac pericyte infection include upregulation of inflammatory chemokine and cytokine expression, type I interferon signaling, mediators of endothelial constriction, and cell death. Collectively, these data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a possible role for pericyte infection in the pathogenesis of COVID-19. Overall design: RNA sequencing of pericytes 4 days post-inoculation. Cardiac pericytes from 3 donors were inoculated with SARS-CoV-2 mNeonGreen at an multiplicity of infection (MOI) of 1 (5 technical replicates/donor) or mock (3 technical replicates/donor).