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

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. [Display omitted] •SARS-CoV-2 damages the heart using blood cells or secreted vesicles (lungs).•Cardiomyocytes are infected via ACE2, TMPRSS2, CTSB/L, integrins, or NRP-1 routes.•Infected myocytes exhibit disorganized contractile elements and release troponin.•SARS-CoV-2 promotes ROS production, impaired calcium signals, and erratic contraction.•COVID-19 treatment and vaccines exert a side effect on cardiac function.