Sex differences underlying preexisting cardiovascular disease and cardiovascular injury in COVID-19

Abstract

The novel 2019 coronavirus disease (COVID-19), resulting from severe acute respiratory syndrome coronarvirus-2 (SARS-CoV-2) infection, typically leads to respiratory failure in severe cases; however, cardiovascular injury is reported to contribute to a substantial proportion of COVID-19 deaths. Preexisting cardiovascular disease (CVD) is among the most common risk factors for hospitalization and death in COVID-19 patients, and the pathogenic mechanisms of COVID-19 disease progression itself may promote the development of cardiovascular injury, increasing risk of in-hospital death. Sex differences in COVID-19 are becoming more apparent as mounting data indicate that males seem to be disproportionately at risk of severe COVID-19 outcome due to preexisting CVD and COVID-19-related cardiovascular injury. In this review, we will provide a basic science perspective on current clinical observations in this rapidly evolving field and discuss the interplay sex differences, preexisting CVD and COVID-19-related cardiac injury.

Keywords: ACE2; Arrhythmia; COVID-19; Cardiovascular; Sex differences; Thrombosis.

Graphical abstract

Fig. 1

Factors underlying preexisting CVD, risk of COVID-19 severity, and COVID-19 related cardiovascular injury in males and females. Preexisting CVD is modulated by sex chromosomes and hormones, ACE2 expression, drug interactions, obesity and smoking, which may predispose males and females differently to COVID-19 severity. CVD, obesity and smoking are risk factors with a higher burden in male vs. female COVID-19 patients (shown with red icons in males). COVID-19 pathogenic mechanisms also contribute to cardiovascular injury. Males exhibit higher burden of cardiac injury than females, while no sex disparities in arrhythmia and microvascular injury and thrombosis have been reported thus far. COVID-19-induced cardiovascular injury is thought to be modulated by sex hormones, ACE2 expression and systemic inflammation, with the latter being more pronounced in males. Altogether, these factors may explain why male COVID-19 patients seem to be at higher risk for severe disease progression and cardiovascular injury compared to females. Red icons reflect sex differences in factors observed in COVID-19 patients, gray icons reflect factors wherein no sex difference has been found in COVID-19 patients or is yet unknown. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)