摘要The fight against coronavirus disease 2019(COVID-19)caused by SARS-CoV-2 infection is still raging.However,the pathophysiology of acute and post-acute manifestations of COVID-19(long COVID-19)is understudied.Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro-and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules.SARS-CoV-2 infection primarily affects the pulmonary system,but accumulating evidence suggests that it also affects the pan-vasculature in the extrapulmonary systems by directly(via virus infection)or indirectly(via cytokine storm),causing endothelial dysfunction(endotheliitis,endothelialitis and endotheliopathy)and multi-organ injury.Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction,including reduced nitric oxide(NO)bioavailability,oxidative stress,endothelial injury,glycocalyx/barrier disruption,hyperpermeability,inflammation/leukocyte adhesion,senescence,endothelial-to-mesenchymal transition(EndoMT),hypercoagulability,thrombosis and many others.Thus,COVID-19 is deemed as a(micro)vascular and endothelial disease.Of translational relevance,several candidate drugs which are endothelial protective have been shown to improve clinical manifestations of COVID-19 patients.The purpose of this review is to provide a latest summary of biomarkers associated with endothelial cell activation in COVID-19 and offer mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro-and micro-vasculature of COVID-19 patients.We envisage further development of cellular models and suitable animal models mimicking endothelial dysfunction aspect of COVID-19 being able to accelerate the discovery of new drugs targeting endothelial dysfunction in pan-vasculature from COVID-19 patients.