The roles and potential therapeutic implications of C5a in the pathogenesis of COVID-19-associated coagulopathy

Highlights

• COVID-19-associated coagulopathy is a leading cause of patient morbidity and multisystem organ failure in COVID-19 patients.

• The pathogenesis of COVID-19-associated coagulopathy be summarized through the prism of Virchow’s triad.

• Complement C5a research with regard to the pathogenesis of COVID-19-associated coagulopathy are summarized in this review.

• Experimentally therapeutic applications of C5a and types of C5a inhibitors are clearly summarized in this review.

Abstract

Emerging evidence has documented that multisystem organ failure in coronavirus disease 2019 (COVID-19) patients is strongly associated with various coagulopathies. Treatments for COVID-19-associated coagulopathy are still a clinical challenge. An advancement in the knowledge of mechanisms of the excessive or inappropriate activation of the complement cascade involved in the genesis of COVID-19-associated coagulopathy might be a fundamental approach for developing novel classes of anticoagulant drugs. In this context, there is emerging evidence indicating that C5a, a component of the complement system, and its receptors (C5aRs) play a critical role in the genesis of the COVID-19-associated hypercoagulable state. Thus, this review describes the mechanisms by which C5a/C5aR signaling participates in the cascade of events involved in the pathophysiology of COVID-19-associated coagulopathy. Furthermore, it highlights the current possibilities for the development of a novel therapeutic approach for COVID-19 patients that targets C5a/C5aRs signaling.