The article discusses the critical role of endothelial cells (ECs) in the progression and severity of COVID-19, particularly in the development of acute respiratory distress syndrome (ARDS). It highlights that ECs contribute to ARDS by altering vessel barrier integrity, promoting a pro-coagulative state, inducing vascular inflammation, and mediating inflammatory cell infiltration. The authors propose that ECs play a central role in the pathogenesis of ARDS and multi-organ failure in severe COVID-19 cases. They also explore mechanisms such as viral infection of ECs, disruption of the ACE2 receptor, activation of neutrophils, and the release of cytokines that lead to increased vascular permeability and coagulation. The article suggests that targeting ECs or vascular normalization strategies could be potential therapeutic approaches to manage the disease. Additionally, it mentions ongoing clinical trials investigating the effects of targeting angiopoietin 2 and bevacizumab in patients with COVID-19.The article discusses the critical role of endothelial cells (ECs) in the progression and severity of COVID-19, particularly in the development of acute respiratory distress syndrome (ARDS). It highlights that ECs contribute to ARDS by altering vessel barrier integrity, promoting a pro-coagulative state, inducing vascular inflammation, and mediating inflammatory cell infiltration. The authors propose that ECs play a central role in the pathogenesis of ARDS and multi-organ failure in severe COVID-19 cases. They also explore mechanisms such as viral infection of ECs, disruption of the ACE2 receptor, activation of neutrophils, and the release of cytokines that lead to increased vascular permeability and coagulation. The article suggests that targeting ECs or vascular normalization strategies could be potential therapeutic approaches to manage the disease. Additionally, it mentions ongoing clinical trials investigating the effects of targeting angiopoietin 2 and bevacizumab in patients with COVID-19.