COVID-19-Associated Hyper-Fibrinolysis: Mechanism and Implementations

Area of Science:

• Virology
• Immunology
• Hematology

Background:

• Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, exhibits high infectivity, morbidity, and mortality.
• COVID-19 pathogenesis involves over-activation of inflammation and coagulation systems, leading to endothelial damage, hemostatic disorders, and acute respiratory distress syndrome (ARDS).
• Elevated circulating cytokines and D-dimer levels are key biomarkers of poor outcomes in COVID-19 patients, indicating hyper-fibrinolysis and hyper-coagulation.

Purpose of the Study:

• To investigate the role of plasmin in COVID-19 pathophysiology, including its involvement in viral entry and ARDS.
• To propose a novel therapeutic strategy for managing fibrinolysis and ARDS in COVID-19 patients.

Main Methods:

• The study reviews existing literature on SARS-CoV-2, COVID-19, inflammation, coagulation, and plasmin.
• It explores the functional similarities between plasmin and TMPRSS2 in viral entry.
• It examines plasmin's role in ARDS and cytokine secretion.

Main Results:

• Plasmin plays a significant role in fibrinolysis and is implicated in the pathophysiology of ARDS in SARS.
• Plasmin can promote the secretion of pro-inflammatory cytokines like IL-6 and TNF from macrophages.
• The study highlights the dual role of plasmin in viral processes and host inflammatory responses.

Conclusions:

• A combination therapy of anti-fibrinolytic drugs and anticoagulants is proposed as a potential treatment for COVID-19.
• This approach aims to alleviate hyper-fibrinolysis and mitigate ARDS in patients with severe COVID-19.
• Further research is warranted to validate this therapeutic strategy.