Crit Care. 2020; 24: 353. Published online 2020 Jun 16. The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection Stéphanie Pons,1,2 Sofiane Fodil,3 Elie Azoulay,3 and Lara Zafrani1,3 Author information: 1INSERM U976, Human Immunology, Pathophysiology and Immunotherapy, Saint-Louis Teaching Hospital, Paris University, Paris, France2Anesthesia and Critical Care Department, Avicenne Teaching Hospital, Assistance Publique des Hôpitaux de Paris, Bobigny, France3Department of Medical Intensive Care Unit, Saint-Louis Teaching Hospital, Assistance Publique des Hôpitaux de Paris, 1, Avenue Claude Vellefaux, 75010 Paris, France Lara Zafrani, Email: rf.phpa@inarfaz.aral. Abstract 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.
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