Cardiovascular Tropism and Sequelae of SARS-CoV-2 Infection

Abstract

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline proposed disease mechanisms, including direct SARS-CoV-2 infection of major cardiovascular cell types and pathogenic effects of non-infectious viral particles and elicited inflammatory mediators. Finally, we identify the major outstanding questions in cardiovascular COVID-19 research.

Keywords: COVID-19; SARS-CoV-2; cardiomyocyte; myocarditis; pericyte; post-acute sequelae of SARS-CoV-2 infection; thrombosis.

Figure 1

The cardiac complications of COVID-19. Cardiac involvement during the clinical course of COVID-19 can manifest as acute myocardial injury with elevated troponin, heart failure with a decreased ejection fraction, myocarditis, cardiac arrhythmia, thromboembolic events and pericarditis. Evidence of cardiac inflammation can also be present in people who seemingly recover from acute illness.

Figure 2

The pathophysiology of cardiac COVID-19. SARS-CoV-2 impacts cardiovascular physiology through the direct infection of cardiac cells, systemic inflammation, and viropathology. Direct infection (top panel) has been described in cardiomyocytes and pericytes. Cardiomyocyte infection results in the loss of sarcomere structure, a decrease in contractile force generation, the release of cytokines and chemokines, and the death of infected cells. In pericytes, SARS-CoV-2 infection causes the production of vasoactive substances and cytokines, and the death of infected cells. Productive replication contributes to further viral dissemination. Severe lung pathology in COVID-19 elicits systemic inflammation (middle panel) that contributes to immune cell recruitment and a prothrombotic state. SARS-CoV-2 virions act as PAMPs that trigger inflammatory responses in the absence of productive infection. This is referred to as viropathology (bottom panel). While poorly understood in the context of the heart, viropathology may regulate the activation of macrophages and endothelial cells, which do not support the replication of SARS-CoV-2. This mechanism can further contribute to immune cell recruitment and the generation of local inflammation within the heart.