Fibrinolysis in COVID-19: Impact on Clot Lysis and Modulation of Inflammation

Title:Fibrinolysis in COVID-19: Impact on Clot Lysis and Modulation of Inflammation

Volume: 23 Issue: 17

Author(s): Michelle A. Sugimoto, Luiza O. Perucci, Luciana P. Tavares, Mauro M. Teixeira and Lirlândia P. Sousa*

Affiliation:

• Signaling in Inflammation Laboratory, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil

Keywords: COVID-19, fibrinolysis, plasminogen, plasmin, inflammation, inflammation resolution, lung injury, ARDS, fibrinolytic drugs, thromboinflammation, immunothrombosis.

Abstract: COVID-19 is a multisystem disease caused by SARS-CoV-2 and is associated with an imbalance between the coagulation and fibrinolytic systems. Overall, hypercoagulation, hypofibrinolysis and fibrin-clot resistance to fibrinolysis predispose patients to thrombotic and thromboembolic events. In the lungs, the virus triggers alveolar and interstitial fibrin deposition, endothelial dysfunction, and pulmonary intravascular coagulation, all events intrinsically associated with the activation of inflammation and organ injury. Adding to the pathogenesis of COVID-19, there is a positive feedback loop by which local fibrin deposition in the lungs can fuel inflammation and consequently dysregulates coagulation, a process known as immunothrombosis. Therefore, fibrinolysis plays a central role in maintaining hemostasis and tissue homeostasis during COVID-19 by cleaning fibrin clots and controlling feed-forward products of coagulation. In addition, components of the fibrinolytic system have important immunomodulatory roles, as evidenced by studies showing the contribution of Plasminogen/Plasmin (Plg/Pla) to the resolution of inflammation. Herein, we review clinical evidence for the dysregulation of the fibrinolytic system and discuss its contribution to thrombosis risk and exacerbated inflammation in severe COVID-19. We also discuss the current concept of an interplay between fibrinolysis and inflammation resolution, mirroring the well-known crosstalk between inflammation and coagulation. Finally, we consider the central role of the Plg/Pla system in resolving thromboinflammation, drawing attention to the overlooked consequences of COVID-19-associated fibrinolytic abnormalities to local and systemic inflammation.

Cite this article as:

Sugimoto A. Michelle, Perucci O. Luiza, Tavares P. Luciana, Teixeira M. Mauro and Sousa P. Lirlândia*, Fibrinolysis in COVID-19: Impact on Clot Lysis and Modulation of Inflammation, Current Drug Targets 2022; 23 (17) . https://dx.doi.org/10.2174/1389450123666221011102250