• Frank L van de Veerdonk, Mihai G Netea, Marcel van Deuren, Jos Wm van der Meer, Quirijn de Mast, Roger J Brüggemann, and Hans van der Hoeven.
• Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands.
• Elife. 2020 Apr 27; 9.

AbstractCOVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. We propose that blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS). In addition, this pathway might indirectly be responsive to anti-inflammatory agents.© 2020, van de Veerdonk et al.

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