Fig. 1.

Pathophysiology of coagulopathy in COVID-19. SARS-CoV-2 enters host cells by interacting its spike protein with the entry receptor ACE2 in the presence of TMPRSS2 (left). The proposed mechanisms for COVID-19 associated coagulopathy include (1) direct virus-mediated cell damage; (2) dysregulation of the RAAS due to downregulation of ACE2 related to viral entry, which leads to decreased cleavage of angiotensin I and angiotensin II. ACE2 cleaves angiotensin II (AngII) to angiotensin 1-7 (Ang1-7). Invasion of the endothelial cells by SARS-CoV-2 causes internalization of the ACE2 receptor, promoting an imbalance of Ang1-7 and AngII, in favor of the latter, resulting in suppression of Ang1-7-mediated vasodilation and accumulation of AngII, which binds to angiotensin II receptor type 1 (AT1), with potential to exacerbate pulmonary vasoconstriction and induction of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) expression on platelets and the endothelium; (3) endothelial cell damage and immunothrombosis or thromboinflammation; and (4) dysregulation of the immune response and hyperinflammation caused by inhibition of interferon signaling by the virus, T cell lymphodepletion, and the production of proinflammatory cytokines, particularly IL-6 and TNF⍺