Abstract 13505: COVID-19 and Cardiovascular Disease Patient Hearts Harbor Sympathetic Remodeling and Altered Angiotensin Converting Enzyme 2 Localization

Abstract

Cardiac complications of COVID-19 have been well described and are associated with significant morbidity and mortality. Concomitantly, various pre-existing cardiovascular diseases (CVDs) are established risk factors for developing severe COVID-19 illness and death. The mechanisms of cardiac injury after COVID-19 remain incompletely understood. Further, whether and how SARS-CoV-2 directly infects the heart is unclear. In this study, we investigated cardiac sympathetic innervation and the cellular localization of angiotensin converting enzyme 2 (ACE2) to test the hypothesis that pre-existing or acute changes in these parameters could contribute to cardiac complications of COVID-19. We performed immunohistochemical (IHC) analysis on sections of left ventricular (LV) wall from twenty autopsied human hearts consisting of a control group, a CVD group, and COVID-19 ARDS and COVID-19 non-ARDS groups. Using tyrosine hydroxylase as a noradrenergic marker, we observed substantial sympathetic nerve loss in CVD LVs compared to the control group, which is consistent with previous work suggesting loss of sympathetic activity in severe heart failure. Additionally, we observed mild and heterogeneous nerve loss in both COVID-19 groups. Using an ACE2 antibody, we observed robust transmural staining localized to pericytes in the control group. The CVD hearts displayed significant loss of ACE2 in pericytes and increased ACE2 in cardiomyocytes. Both COVID-19 groups displayed a modest increase in cardiomyocyte ACE2 compared to controls, and pericyte ACE2 staining was generally maintained. We also performed IHC for PDGF receptor β, an established marker for pericytes, and confirmed ACE2 localization to pericytes. The observed sympathetic nerve remodeling could play a key role in arrhythmogenesis in acute or post-acute COVID-19 patients. Further, if SARS-CoV-2 does infect the heart, then our data demonstrate the primary target would be through microvasculature associated pericytes, not cardiomyocytes. Finally, the upregulation of cardiomyocyte ACE2 in both CVD and COVID-19 groups could play a contributing role in COVID-19 associated cardiac injury or a compensatory role in cardiac pathogenesis by attenuating the local effects of angiotensin II.