Damage to endothelial barriers and its contribution to long COVID

The world continues to contend with COVID-19, fueled by the emergence of viral variants. At the same time, a subset of convalescent individuals continues to experience persistent and prolonged sequelae, known as long COVID. Clinical, autopsy, animal and in vitro studies all reveal endothelial injury in acute COVID-19 and convalescent patients. Endothelial dysfunction is now recognized as a central factor in COVID-19 progression and long COVID development. Different organs contain different types of endothelia, each with specific features, forming different endothelial barriers and executing different physiological functions. Endothelial injury results in contraction of cell margins (increased permeability), shedding of glycocalyx, extension of phosphatidylserine-rich filopods, and barrier damage. During acute SARS-CoV-2 infection, damaged endothelial cells promote diffuse microthrombi and destroy the endothelial (including blood-air, blood-brain, glomerular filtration and intestinal-blood) barriers, leading to multiple organ dysfunction. During the convalescence period, a subset of patients is unable to fully recover due to persistent endothelial dysfunction, contributing to long COVID. There is still an important knowledge gap between endothelial barrier damage in different organs and COVID-19 sequelae. In this article, we mainly focus on these endothelial barriers and their contribution to long COVID.

Automated summary

The emergence of viral variants has resulted in the ongoing global battle against COVID-19, while a subset of convalescent individuals continues to experience persistent and prolonged sequelae known as long COVID. Various studies demonstrate endothelial injury in acute COVID-19 and convalescent patients, highlighting its central role in the progression of COVID-19 and development of long COVID. Different organs possess different types of endothelia with specific features, forming distinct endothelial barriers and executing diverse physiological functions. Endothelial injury leads to increased permeability, glycocalyx shedding, extension of phosphatidylserine-rich filopods, and barrier damage. This article primarily focuses on these endothelial barriers and their contribution to long COVID.