Figure 1. Cross-talk between kinin, complement, and coagulation systems.

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.