In severe SARS-CoV-2 infections, emerging data including recent histopathological studies have emphasized the crucial role of endothelial cells (ECs) in vascular dysfunction, immunothrombosis, and inflammation. Histopathological studies have evidenced direct viral infection of ECs, endotheliitis with diffuse endothelial inflammation, and micro- and macrovascular thrombosis both in the venous and arterial circulations. Venous thrombotic events, particularly pulmonary embolism, with elevated D-dimer and coagulation activation are highly prevalent in COVID-19 patients. The pro-inflammatory cytokine storm, with elevated levels of interleukin-6 (IL-6), IL-2 receptor, and tumor necrosis factor-α, could also participate in endothelial dysfunction and leukocyte recruitment in the microvasculature. COVID-19-induced endotheliitis may explain the systemic impaired microcirculatory function in different organs in COVID-19 patients. Ongoing trials directly and indirectly target COVID-19-related endothelial dysfunctions: i.e., a virus-cell entry using recombinant angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS-2) blockade, coagulation activation, and immunomodulatory therapies, such as anti-IL-6 strategies. Studies focusing on endothelial dysfunction in COVID-19 patients are warranted as to decipher their precise role in severe SARS-CoV-2 infection and organ dysfunction and to identify targets for further interventions.
【저자키워드】 COVID-19, SARS-CoV-2, Cytokines, thrombosis, Endothelial dysfunction, endothelial cells, 【초록키워드】 Inflammation, ACE2, Trial, IL-6, Infection, interleukin-6, D-dimer, protease, angiotensin-converting enzyme 2, Endotheliitis, immunothrombosis, Coagulation, infections, organ dysfunction, target, vascular dysfunction, recruitment, Thrombotic events, COVID-19 patients, Endothelial cell, COVID-19 patient, Immunomodulatory therapies, leukocyte, tumor necrosis factor-α, endothelial, IL-2 receptor, Activation, transmembrane, blockade, organ, direct viral infection, serine 2, venous, prevalent, severe SARS-CoV-2, anti-IL-6, pro-inflammatory cytokine storm, identify, elevated, histopathological, evidenced, explain, microcirculatory function, 【제목키워드】 Infection, organ dysfunction, Vascular, severe SARS-CoV-2,