Abstract:
Cardiovascular dysfunction and disease are common and frequently fatal complications of
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Indeed, from
early on during the SARS-CoV-2 virus pandemic it was recognized that cardiac
complications may occur, even in patients with no underlying cardiac disorders, as part
of the acute infection, and that these were associated with more severe disease and
increased morbidity and mortality. The most common cardiac complication is acute
cardiac injury, defined by significant elevation of cardiac troponins. The potential
mechanisms of cardiovascular complications include direct viral myocardial injury,
systemic inflammation induced by the virus, sepsis, arrhythmia, myocardial oxygen
supply-demand mismatch, electrolyte abnormalities, and hypercoagulability. This review
is focused on the prevalence, risk factors and clinical course of COVID-19-related
myocardial injury, as well as on current data with regard to disease pathogenesis,
specifically the interaction of platelets with the vascular endothelium. The latter section
includes consideration of the role of SARS-CoV-2 proteins in triggering development of a
generalized endotheliitis that, in turn, drives intense activation of platelets. Most
prominently, SARS-CoV-2–induced endotheliitis involves interaction of the viral spike
protein with endothelial angiotensin-converting enzyme 2 (ACE2) together with alternative
mechanisms that involve the nucleocapsid and viroporin. In addition, the mechanisms by
which activated platelets intensify endothelial activation and dysfunction, seemingly driven
by release of the platelet-derived calcium-binding proteins, SA100A8 and SA100A9, are
described. These events create a SARS-CoV-2–driven cycle of intravascular inflammation
and coagulation, which contributes significantly to a poor clinical outcome in patients with
severe disease.
