The interplay between inflammation and thrombosis in COVID-19: Mechanisms, therapeutic strategies, and challenges.

Coronavirus disease 2019 (COVID-19), caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can cause life-threatening pathology characterized by a dysregulated immune response and coagulopathy. While respiratory failure induced by inflammation is the most common cause of death, micro-and macrovascular thrombosis leading to multiple organ failure are also causes of mortality. Dysregulation of systemic inflammation observed in severe COVID-19 patients is manifested by cytokine release syndrome (CRS) - the aberrant release of high levels of proinflammatory cytokines, such as IL-6, IL-1, TNFα, MP-1, as well as complement. CRS is often accompanied by activation of endothelial cells and platelets, coupled with perturbation of the balance between the pro-and antithrombotic mechanisms, resulting in thrombosis. Inflammation and thrombosis form a vicious circle, contributing to morbidity and mortality. Treatment of hyperinflammation has been shown to decrease thrombosis, while anti-thrombotic treatment also downregulates cytokine release. This review highlights the relationship between COVID-19-mediated systemic inflammation and thrombosis, the molecular pathways involved, the therapies targeting these processes, and the challenges currently encountered.