Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands
Mihai G Netea
Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands; Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
Marcel van Deuren
Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands
Jos WM van der Meer
Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands
Quirijn de Mast
Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands
Roger J Brüggemann
Department of Pharmacy, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands
Hans van der Hoeven
Intensive Care, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands
COVID-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.
