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.
