Complement and coagulation: key triggers of COVID-19–induced multiorgan pathology
Berhane Ghebrehiwet, Ellinor I. Peerschke
Berhane Ghebrehiwet, Ellinor I. Peerschke
Published September 14, 2020
Citation Information: J Clin Invest. 2020;130(11):5674-5676. https://doi.org/10.1172/JCI142780.
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Commentary

Complement and coagulation: key triggers of COVID-19–induced multiorgan pathology

Abstract

In a stunningly short period of time, the unexpected coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2), has turned the unprepared world topsy-turvy. Although the rapidity with which the virus struck was indeed overwhelming, scientists throughout the world have been up to the task of deciphering the mechanisms by which SARS–CoV-2 induces the multisystem and multiorgan inflammatory responses that, collectively, contribute to the high mortality rate in affected individuals. In this issue of the JCI, Skendros and Mitsios et al. is one such team who report that the complement system plays a substantial role in creating the hyperinflammation and thrombotic microangiopathy that appear to contribute to the severity of COVID-19. In support of the hypothesis that the complement system along with neutrophils and platelets contributes to COVID-19, the authors present empirical evidence showing that treatment with the complement inhibitor compstatin Cp40 inhibited the expression of tissue factor in neutrophils. These results confirm that the complement axis plays a critical role and suggest that targeted therapy using complement inhibitors is a potential therapeutic option to treat COVID-19–induced inflammation.

Authors

Berhane Ghebrehiwet, Ellinor I. Peerschke

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Figure 1

Cross-talk between kinin, complement, and coagulation systems.

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Cross-talk between kinin, complement, and coagulation systems. SARS–CoV-...
SARS–CoV-2 binding to ACE2 prevents degradation of bradykinin to dysregulate vasodilation. Kallikrein activates polypeptides to ultimately release bradykinin (BK), which results in vasodilation. Additionally, kallikrein activates the complement cascade and mediates the plasminogen cascade. Plasmin is a serine protease of plasma, which can regulate both the complement and coagulation systems. Although the major function of plasmin is to degrade fibrin clots in a process called fibrinolysis, it is also able to degrade a wide range of plasma proteins, including complement proteins, thereby generating activation fragments such as C3a and C5a that contribute to the cytokine storm and aggravation of the inflammatory process.