Figure 26.

Schematic of SARS-CoV-2 infection in endothelial cells in patients at risk, and the subsequent mechanisms leading to the thrombotic events. Endothelial cells are expressing the receptor ACE2 and then are direct target for SARS-CoV-2 infection once it has reached the vascular system. Direct consequences of endothelial cells infection are the endothelium damage and dysfunction, endothelium inflammation (endotheliitis), both leading to the activation of a pro-coagulant state. Other consequence of SARS-CoV-2 infection is the increased production of Ang II (as consequence of ACE2 inactivation after internalization), with a vasoconstriction effect. The combination of the activation of pro-coagulation and vasonconstriction is then associated with a high risk of thrombotic events. The majority of patients at risk present a pre-existing pro-coagulant state due to (1) hyperglycemia-induced increase in AGEs production, (2) increased level of pro-coagulant factor such as fibrinogen. In addition, all group at risk are also described to present a pre-existing increased level of Ang II. Then, the presence of these pre-existing conditions (pro-coagulant factors and Ang II level) easily explain the increased risk of thrombotic events upon SARS-CoV-2 infection in these groups of patients. Moreover, and as previously described, the majority of patients at-risk for COVID-19 presents a hyperglycemia or an IGT that increase the viral replication rate in cells. Then, these patients may also present an increased infection rate in their endothelial cells further amplifying the associated events above described. Hence, this schema highlights why these specific groups of patients present a high proportion of severe micro and macro-vascular thrombotic events upon SARS-CoV-2 infection.