Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications

Abstract

Coronavirus disease 2019 (COVID-19) has been declared a pandemic on 11 March 2020 by the WHO. Despite being mainly a respiratory virus, cardiac complications have been described. These range from sudden cardiac death to subtle diastolic dysfunction after recovery from COVID-19. The commonest cardiac presentation to date is acute heart failure resulting from biventricular or left ventricular hypokinesis and elevation of cardiac troponins. It has been shown that COVID-19 downregulates angiotensin-converting enzyme-2, which has protective effects on the endothelium and cardiomyocytes. It has also been proven that COVID-19 induces a state of hypercytokinaemia, some cytokines such as interleukin-1 and interleukin-6 have an injurious effect on the myocardium and endothelium, respectively. Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction. The understanding and linking of such mechanisms might help in tailoring drug repurposing for treatment or prophylaxis of COVID-19 cardiovascular complications.

Keywords: angiotensin-converting enzyme 2; cardiomyocytes; coronavirus disease 2019; drug repurposing; endothelium; paracrine effect of cytokines.

Fig. 1

Summary of COVID-19 mechanisms in targeting cardiovascular system. ACE 2, angiotensin converting enzyme 2; AG 1-7, angiotensin 1-7; COVID-9, coronavirus-2019; HMB-1, high mobility box-1; IL-1, interleukin-1; IL-6, interleukin-6; JAK/STAT, janus kinase/signal transducer and activator of transcription; NO, nitric oxide.