ecallantide and Coronavirus-Infections

To date the pathophysiology of COVID-19 remains unclear: this represents a factor determining the current lack of effective treatments. In this paper, we hypothesized a complex host response to SARS-CoV-2, with the Contact System (CS) playing a pivotal role in innate immune response. CS is linked with different proteolytic defense systems operating in human vasculature: the Kallikrein-Kinin (KKS), the Coagulation/Fibrinolysis and the Renin-Angiotensin (RAS) Systems. We investigated the role of the mediators involved. CS consists of Factor XII (FXII) and plasma prekallikrein (complexed to high-molecular-weight kininogen-HK). Autoactivation of FXII by contact with SARS-CoV-2 could lead to activation of intrinsic coagulation, with fibrin formation (microthrombosis), and fibrinolysis, resulting in increased D-dimer levels. Activation of kallikrein by activated FXII leads to production of bradykinin (BK) from HK. BK binds to B2-receptors, mediating vascular permeability, vasodilation and edema. B1-receptors, binding the metabolite [des-Arg

Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; Bradykinin; Capillary Permeability; Complement C1 Inhibitor Protein; Coronavirus Infections; COVID-19; Factor XIIa; Fibrinolysis; Host-Pathogen Interactions; Humans; Kallikrein-Kinin System; Kininogen, High-Molecular-Weight; Pandemics; Peptidyl-Dipeptidase A; Plasma Kallikrein; Pneumonia, Viral; Prekallikrein; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Renin-Angiotensin System; SARS-CoV-2; Vasodilation