Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection

Cardiac Pericytes

“…Brumback et al 8 also demonstrated that their cultured human cardiac pericytes harbor substantial levels of ACE-2, cathepsin H, cathepsin L, and furin, but undetectable levels of TMPRSS2 and TMPRSS4. Similar to cardiomyocytes, 10 pericytes were targeted by SARS-CoV-2 via ACE-2 and endosomal pathways without involvement of TMPRSS2 or TMPRSS4, because infection could be blocked by an ACE-2 antibody, a cysteine protease inhibitor, E-64, and bafilomycin-A1, which inhibits the acidification of cysteine proteases like cathepsins.…”

“…In this issue of JACC: Basic to Translational Science , Brumback et al 8 demonstrate convincingly that human cardiac pericytes, and not endothelial cells, are permissive to SARS-CoV-2 infection. The authors derived primary human cardiac pericytes from organotypic cardiac slices of nonfailing human ventricles.…”

“…Brumbach et al 8 showed that viral entry into cardiac pericytes upregulated inflammatory signaling (type I interferon), innate immunogenic responses, and vasoactive genes. Strikingly, interleukin-6 was robustly enhanced, as has been shown in COVID-19 cases.…”

“…In future studies, it will be important to determine whether the downstream effects of pericyte infection and cross-talk with endothelial cells may lead to the development of microthrombosis, including the effects of platelet-derived growth factor-β, which is an important mediator of endothelial and pericyte cross-talk. Type I IFN-γ signaling seems to be the common pathway elicited in both human cardiac pericytes 8 and cardiomyocytes 10 upon infection by SARS-CoV-2. Both cardiomyocytes and cardiac pericytes are susceptible to SARS-CoV-2 infection in an ACE-2 and endosomal pathway dependent manner, but cells may have differing levels of ACE-2.…”

“…Focused investigations that reveal the underlying molecular mechanisms responsible for the cardiovascular complications of COVID-19 remain critically important. The study by Brumbach et al 8 in this issue of the JACC: Basic to Translational Science places human cardiac pericytes in the limelight so that they may be considered in the context of vascular dysfunction and myocarditis that is observed in patients with COVID-19. The findings in the present study implicate pericytes as a key cell type that mediates the cardiovascular and thrombotic complications of COVID-19.…”