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 signalling 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.

Risk of Cardiovascular Events After COVID-19

“…23 The distinct mechanism of SARS-CoV-2 infection includes ACE2 downregulation, diminishing the protective, antiinflammatory role of ACE2, facilitating myocardial injury and fibrosis as the virus' long-term sequelae. 24 Frequently observed nonspecific cardiac pathology in COVID-19 highlights the importance of appropriate control in study design assessing CV risks of SARS-CoV-2 infection. 25,26 Of note, any pandemic or epidemic, regardless of the type of a pathogen, might be associated with increased CV mortality.…”

COVID-19 and the cardiovascular system-current knowledge and future perspectives

“…The pathophysiological mechanisms by which the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) impacts the myocardium is still under investigation[ 6 ]. Cardiac cells express the angiotensin-converting enzyme 2 (ACE2) receptor through which the SARS-CoV-2 can bind and cause direct cardiac impairment and dysfunction of endothelial cells of coronary vessels[ 7 ].…”

The Impact of the COVID-19 Pandemic on the Organization of Cardio-Hematology Care—A Polish Single Center Experience

“…COVID-19 cardiac symptoms may include myocarditis, myocardial infarction, heart failure, acute coronary syndrome, and arrhythmia. Various signaling pathways could be altered in the infected cardiomyocytes, causing cardiac dysfunction as heart tissue shows high levels of necessary accessory proteins such as ACE2, NRP-1, TMPRSS2, CD147, integrin α5β1, and CTSB/L, which are targets of the SARS-CoV-2 virus [ 14 ].…”