Calming the storm: treating hypercoagulability and hyperinflammation in patients with COVID-19 (CALMING)

 COVID-19 patients with hyperinflammation, hypercoagulability and hyperfibrinolysis are at increased risk for severe disease and mortality. Local dysfucntion of the viral receptor protein ACE2, which degrades the vasoactive peptides bradykinines, results in accumulation of vasoactive and inflammatory mediators that cause vasodilation and alveolar edema, leading to hypoxic respiratory failure and to activation of local and systemic inflammatory pathways through the activation of bradykinin receptors and interleukin-1 pathway. The current project includes a pilot descriptive study and a multicenter randomized clinical intervention trial in patients with COVID-19. In a pilot study, BAL and plasma samples from patients with COVID-19 are analyzed to describe the local and systemic inflammatory response. In a multicenter randomized clinical intervention trial in patients with confirmed COVID-19 requiring hospitalisation, we will study the feasibility, safety, and efficacy of a multistep intervention to suppress coagulation and hyperinflammation.