Fig. 2

Overview of endothelial activation and dysfunction in the pathogenesis of COVID-19. In the initial stage of severe COVID-19 patients, SARS-CoV-2 infection causes acute lung injury, and then excessive cytokines are released from immune cells, bronchial epithelial cells, and alveolar cells. SARS-CoV-2 infection and various cytokines are predicted to cause endothelial activation and dysfunction by multiple pathways, leading to vascular inflammation and permeability. Then more immune cells enter or migrate into alveoli and enhance lung inflammation. With vascular permeability, erythrocytes enter into alveoli, leading to edema. Moreover, with the release of pro-inflammatory cytokines and inflammatory cells to circulation, vasculitis occurs. The disruption of vascular integrity and EC apoptosis leads to the exposure of the thrombogenic basement membrane and the activation of the clotting cascade. Endothelial cells release relevant cytokines that further augment platelet production. Platelet activation is the primary cause of thrombosis. Inflammation, edema, and microthrombus work together to cause ARDS. The transfer of microthrombi into the blood circulation increases the risk of the formation of deep vein thrombosis, which may further cause pulmonary embolism and stroke