Long-term effect of SARS-CoV-2 infection on cardiovascular outcomes and all-cause mortality

Abstract

Since the very beginning of the coronavirus disease 2019 (COVID-19) pandemic in early 2020, it was evident that patients with cardiovascular disease (CVD) were at an increased risk of developing severe illness, and complications spanning cerebrovascular disorders, dysrhythmias, acute coronary syndrome, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, thromboembolic disease, stroke, and death. Underlying these was excessive systemic inflammation and coagulopathy due to SARS-COV-2 infection, the effects of which also continued long-term as evidenced by post-COVID-19 cardiovascular complications. The acute and chronic cardiovascular effects of COVID-19 occurred even among those who were not hospitalized and had no previous CVD or those with mild symptoms. This comprehensive review summarizes the current understanding of molecular mechanisms triggered by the SARS-CoV-2 virus on various cells that express the angiotensin-converting enzyme 2, leading to endothelial dysfunction, inflammation, myocarditis, impaired coagulation, myocardial infarction, arrhythmia and a multisystem inflammatory syndrome in children or Kawasaki-like disease.

Keywords: COVID-19; Endothelial dysfunction; Inflammation; Myocardial injury; Oxidative stress; Thrombosis.

Graphical abstract

Fig. 1

Schematic representation of the effects of SARS-CoV-2 on the renin-angiotensin system. SARS-CoV-2 reduces the expression of ACE2 and as a consequence leads to the accumulation of Ang II. Ang II promotes an inflammatory state through the release of cytokines. ACE2, angiotensin-converting enzyme 2; Ang II, angiotensin II.

Fig. 2

Schematic representation of SARS-CoV-2-mediated endothelial dysfunction. An increase in cytokine production, coagulation factors, and a decrease in nitric oxide lead to altered microcirculation, tissue hypoxia, and injury.

Fig. 3

Cardiovascular complications due to SARS-CoV-2 infection. Schematic representation of molecular mechanisms induced by SARS-CoV-2 and the subsequent cardiac complications whose incidence is increased in the population after infection.

Fig. 4

Histopathological representation of infiltrated immune response cells. (a) Early contraction band necrosis. Hypercontraction of the myofibers with myofibrillar break and formation of cross bands (H&E 40×); (b) infiltrates of CD45+ cells (10×); (c) infiltrates of CD68+ macrophages (10×); (d) infiltrates with CD4+ T cells (40×).

Fig. 5

Myocardial infarction as a consequence of SARS-CoV-2 infection. Schematic representation of how SARS-CoV-2 by multiple mechanisms causes myocardial infarction.