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SARS-CoV-2 engagement of ACE-2 blocks ANG II breakdown into ANG 1-7, increasing intracellular ANG II. ANG II signaling via angiotensin 1 receptors (AT-1Rs) (inhibited by ARBs), induces EC senescence and upregulates IL-6 and ROS, causing immune, and coagulation dysfunction. When ACE-2 is bound by the virus, the SARS-CoV-2/ACE-2 complexes enter host cells by endocytosis. Complexes that are not endocytosed are shed by ADAM17, contributing to critical illness.
