THE PROTHROMBOTIC STATE ASSOCIATED WITH SARS-COV-2 INFECTION: PATHOPHYSIOLOGICAL ASPECTS COVID and Thrombosis

Main Article Content

Nicola Semeraro
Prof. Mario Colucci

Keywords

SARS-COV-2, Thrombosis, COVID, Infection, Prothrombotic state

Abstract

Severe coronavirus disease-2019 (COVID-19) is frequently associated with microvascular thrombosis, especially in the lung, or macrovascular thrombosis, mainly venous thromboembolism, that significantly contribute to the mortality burden of the disease. COVID-19 patients also exhibit distinctive laboratory abnormalities that are compatible with a prothrombotic state. The key event underlying COVID-19-associated thrombotic complications is an excessive host inflammatory response to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection generating multiple inflammatory mediators, mainly cytokines and complement activation products. The latter, along with the virus itself, the increased levels of angiotensin II and hypoxia, drive the major cellular changes promoting thrombosis, which include: (1) aberrant expression of tissue factor by activated alveolar epithelial cells, monocytes-macrophages and neutrophils, and production of other prothrombotic factors by activated endothelial cells (ECs) and platelets; (2) reduced expression of physiological anticoagulants by dysfunctional ECs, and (3) suppression of fibrinolysis by the endothelial overproduction of plasminogen activator inhibitor-1 and, likely, by heightened thrombin-mediated activation of thrombin-activatable fibrinolysis inhibitor. Moreover, neutrophils and other cells, upon activation or death, release nuclear materials which are endowed with potent prothrombotic properties. The ensuing thrombosis significantly contributes to lung injury and, in most severe COVID-19 patients, to multiple organ dysfunction. Insights into the pathogenesis of COVID-19-associated thrombosis may have implications for the development of new diagnostic and therapeutic tools.

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