Endothelial activation and dysfunction in COVID-19: frombasic mechanisms to potential therapeutic approaches

On 12 March 2020,the outbreak of coronavirus disease 2019(COVID-19)was declared a pandemic by the World Health Organization.As of 4 August 2020,more than 18 million confirmed infections had been reported globally.Most patients have mild symptoms,but some patients develop respiratory failure which is the leading cause of death among COVID-19 patients.Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation.Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier,promoting pro-coagulative state,inducing endothelial inflammation,and even mediating leukocyte infiltration.This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.