SARS-CoV-2 reinfection: Adding insult to dysfunctional endothelium in patients with atherosclerotic cardiovascular disease

Abstract

In this short narrative review, we aim at defining the pathophysiological role endothelial dysfunction in the observed COVID-19-associated rise in risk of cardiovascular disease. Variants of the SARS-CoV-2 virus have caused several epidemic waves of COVID-19, and the emergence and rapid spread of new variants and subvariants are likely. Based on a large cohort study, the incidence rate of SARS-CoV-2 reinfection is about 0.66 per 10 000 person-weeks. Both the first infection and reinfection with SARS-CoV-2 increase cardiac event risk, particularly in vulnerable patients with cardiovascular risk factors and the accompanying systemic endothelial dysfunction. By worsening pre-existing endothelial dysfunction, both the first infection and reinfection with ensuing COVID-19 may turn the endothelium procoagulative and prothrombotic, and ultimately lead to local thrombus formation. When occurring in an epicardial coronary artery, the risk of an acute coronary syndrome increases, and when occurring in intramyocardial microvessels, scattered myocardial injuries will ensue, both predisposing the COVID-19 patients to adverse cardiovascular outcomes. In conclusion, considering weakened protection against the cardiovascular risk-enhancing reinfections with emerging new subvariants of SARS-CoV-2, treatment of COVID-19 patients with statins during the illness and thereafter is recommended, partly because the statins tend to reduce endothelial dysfunction.

Keywords: Atherosclerotic cardiovascular disease; COVID-19; Endothelial dysfunction; Familial hypercholesterolemia; Omicron; SARS-CoV-2 reinfection.

Fig. 1

Long-standing endothelial dysfunction and its pharmacotherapeutic mitigation in COVID-19 patients. The diagram shows a two-hit scenario for the worsening of cardiac endothelial dysfunction in COVID-19 patients with pre-existing cardiovascular comorbidities. In untreated or undertreated patients with an increased risk for cardiovascular diseases, the traditional cardiometabolic risk factors induce and maintain permanent systemic endothelial dysfunction. Both primary and secondary SARS-CoV-2 infections with ensuing COVID-19 and the associated cytokine storm and viral infection of the endothelial cells further aggravate the pre-existing endothelial dysfunction. Ultimately, thrombosis in an atherosclerotic epicardial coronary artery may lead to acute coronary syndrome and associated acute myocardial infarction, while thrombosis in myocardial microvessels may lead to diffuse myocardial damage. Among the preventive/therapeutic pharmacotherapies for endothelial dysfunction and its pathophysiological and clinical sequelae is the lowering of plasma LDL-cholesterol levels with statins that may mitigate inflammation and reduce platelet thrombus formation also via their pleiotropic effects.