Results published by University of Leuven researchers in eBioMedicine

Markers of inflammation and coagulation are predictors for clinical outcomes in patients with COVID-19. Binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the angiotensin converting enzyme 2 receptor, which is involved in kinin breakdown, could interfere with the kallikrein-kinin pathway. SARS-CoV-2 induced dysregulation of this pathway, which links inflammation and coagulation, could be a key trigger for the initial pathophysiological changes that cause severe lung disease. One randomized controlled trial and two small case-control studies indeed observed
improvement of length of hospital stay and COVID-19 disease markers, respectively, after kallikrein-kinin pathway inhibition.

Paper’s data show increased kallikrein activity, higher levels of the most stable kinin peptide bradykinin-(1-5), and higher levels of neutrophil extracellular traps (NETs) in bronchoalveolar lavage fluid samples from patients with severe COVID-19 compared to those in patients without COVID-19.

Furthermore, in vitro data hint towards a FXII-dependent activation of plasma kallikrein by NET components, thus improving understanding of how NETs and the kallikrein-kinin system could be interconnected.

These findings may help to explain the clinical presentation and contribute to understanding
thromboinflammatory mechanisms in patients with severe pulmonary disease.

Data encourage the investigation of drugs that target the kallikrein-kinin system as a potential treatment
option for patients with severe pulmonary disease, especially for those with strong thromboinflammatory
responses as observed in COVID-19.

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