Endothelial Dysfunction in COVID‐19: A Unifying Mechanism and a Potential Therapeutic Target

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS‐CoV‐2 could be responsible for coronavirus disease 2019 (COVID‐19), which goes from a flu‐like illness to a potentially fatal condition that needs intensive care. Furthermore, the persistence of functional disability and long‐term cardiovascular sequelae in COVID‐19 survivors suggests that convalescent patients may suffer from post‐acute COVID‐19 syndrome, requiring long‐term care and personalized rehabilitation. However, the pathophysiology of acute and post‐acute manifestations of COVID‐19 is still under study, as a better comprehension of these mechanisms would ensure more effective personalized therapies. To date, mounting evidence suggests a crucial endothelial contribution to the clinical manifestations of COVID‐19, as endothelial cells appear to be a direct or indirect preferential target of the virus. Thus, the dysregulation of many of the homeostatic pathways of the endothelium has emerged as a hallmark of severity in COVID‐19. The aim of this review is to summarize the pathophysiology of endothelial dysfunction in COVID‐19, with a focus on personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction as an attractive therapeutic option in this clinical setting.