Interaction of SARS-CoV-2 with cardiomyocytes: Insight into the underlying molecular mechanisms of cardiac injury and pharmacotherapy

Abstract

SARS-CoV-2 causes respiratory illness with a spectrum of systemic complications. However, the mechanism for cardiac infection and cardiomyocyte injury in COVID-19 patients remains unclear. The current literature supports the notion that SARS-CoV-2 particles access the heart either by the circulating blood cells or by extracellular vesicles, originating from the inflamed lungs, and encapsulating the virus along with its receptor (ACE2). Both cardiomyocytes and pericytes (coronary arteries) express the necessary accessory proteins for access of SARS-CoV-2 particles (i.e. ACE2, NRP-1, TMPRSS2, CD147, integrin α5β1, and CTSB/L). These proteins facilitate the SARS-CoV-2 interaction and entry into the pericytes and cardiomyocytes thus leading to cardiac manifestations. Subsequently, various signaling pathways are altered in the infected cardiomyocytes (i.e. increased ROS production, reduced contraction, impaired calcium homeostasis), causing cardiac dysfunction. The currently adopted pharmacotherapy in severe COVID-19 subjects exhibited side effects on the heart, often manifested by electrical abnormalities. Nonetheless, cardiovascular adverse repercussions have been associated with the advent of some of the SARS-CoV-2 vaccines with no clear mechanisms underlining these complications. We provide herein an overview of the pathways involved with cardiomyocyte in COVID-19 subjects to help promoting pharmacotherapies that can protect against SARS-CoV-2-induced cardiac injuries.

Keywords: Cardiac disease; Cardiomyocyte; Infection; SARS-CoV-2; Treatment; Vaccine.

Graphical abstract

Fig. 1

Proposed access routes for SARS-CoV-2 particles to the heart. Following access to the lung, SARS-CoV-2 induces an inflammatory reaction leading to the release of inflammatory mediators and recruitment of inflammatory cells (A). SARS-CoV-2 particles exit pulmonary tissues via extracellular vesicles, or in circulating blood cells as “Trojan Horse”. (B) SARS-CoV-2 can either infect pericytes or cardiomyocytes since both express necessary proteins for this process, thus leading to cardiac abnormalities. (C) Myocarditis has been noticed in vaccinated individuals using both the mRNA or the virus-based vaccines.