Evaluation of the mechanisms of hemostasis activation in COVID-19 and its modulation by bradykinin inhibitors

Serious forms of COVID-19 are characterized by intense activation of inflammation associated with a significant increase in the levels of hemostasis activation markers. According to the theoretical model of immunothrombosis, hemostasis and inflammation are inseparable elements of the innate response to pathogens. According to this model, when regulated, the activation of hemostasis contributes to the eradication of pathogens; but when deregulated, it can lead to secondary damage, such as the formation of thrombi in the microcirculation. It is interesting to highlight that the activation of hemostasis during inflammation occurs by means different from those activated in response to the loss of continuity of the endothelial line observed in post-traumatic bleeding, and involves elements such as the expression of tissue factor in monocytes and microparticles, the activation of intrinsic via DNA released from extracellular neutrophil networks, among others. In addition, breaking the endothelial barrier, which also contributes to the host's response to injury by mediating diapedesis, can be a secondary mechanism of injury, contributing to changes in the alveolar-capillary barrier or even to the activation of hemostasis. In this project, we will evaluate a panel of parameters linked to the activation of hemostasis and the regulation of the integrity of the endothelial barrier in patients with COVID-19 included in a clinical study that will evaluate the effect of bradykinin inhibitors on the clinical course of this disease. The panel will be evaluated at different times in the course of the disease (admission, days +4, +12 and +28), and the allocation by groups will allow conclusions about the evolution of the disease in patients on supportive treatment, or under use of bradykinin, which have the potential to modulate both the regulation of the integrity of the endothelial barrier, and the crosstalk between inflammation and the intrinsic coagulation pathway.