Cardiovascular complications of COVID-19

Abstract

The emergence of the novel SARS coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in an unprecedented pandemic that has been accompanied by a global health crisis. Although the lungs are the main organs involved in COVID-19, systemic disease with a wide range of clinical manifestations also develops in patients infected with SARS-CoV-2. One of the major systems affected by this virus is the cardiovascular system. The presence of preexisting cardiovascular disease increases mortality in patients with COVID-19, and cardiovascular injuries, including myocarditis, cardiac rhythm abnormalities, endothelial cell injury, thrombotic events, and myocardial interstitial fibrosis, are observed in some patients with COVID-19. The underlying pathophysiology of COVID-19-associated cardiovascular complications is not fully understood, although direct viral infection of myocardium and cytokine storm have been suggested as possible mechanisms of myocarditis. In this Review, we summarize available data on SARS-CoV-2-related cardiac damage and discuss potential mechanisms of cardiovascular implications of this rapidly spreading virus.

Figure 1. Possible mechanisms of acute myocardial injury and myocarditis in SARS-CoV-2 infection.

Two main mechanisms by which SARS-CoV-2 causes myocardial injury are direct virus-induced damage and secondary damage due to cytokine storm and inflammatory responses. (A) There is evidence that cardiomyocytes express the receptors required for SARS-CoV-2 entry to the cell. Transmembrane protease TMPRSS2 cleaves the SARS-CoV-2 spike (S) protein, thus facilitating its activation and binding to cell-entry receptor angiotensin converting enzyme 2 (ACE2). (B) In addition, pericytes, which are abundant in cardiac tissue and required for endothelial cell (EC) function and maintenance, express ACE2. Injury of these cells by SARS-CoV-2 results in EC dysfunction. (C) Furthermore, cytokine storm and systemic inflammatory responses initiated by the virus can also lead to cardiac tissue damage and myocarditis. Illustrated by Rachel Davidowitz.

Figure 2. SARS-CoV-2 and endothelial cell dysfunction.

Direct damage to endothelial cells (ECs) caused by SARS-CoV-2 disrupts cell integrity, resulting in EC activation and vascular leakage. Consequent exposure of vWF, which is involved in platelet aggregation and fibrin formation, leads to thrombus formation. Cytokines secreted by activated ECs can further augment the vascular inflammation, permeability, and leakage. Illustrated by Rachel Davidowitz.