Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome

Author:

van de Veerdonk Frank L1ORCID,Netea Mihai G12,van Deuren Marcel1,van der Meer Jos WM1,de Mast Quirijn1,Brüggemann Roger J3,van der Hoeven Hans4

Affiliation:

1. Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands

2. Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany

3. Department of Pharmacy, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands

4. Intensive Care, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands

Abstract

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.

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference23 articles.

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3. An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies;Ceravolo;PLOS ONE,2014

4. European Medicines Agency. 2014. London, UK: European Medicines Agency. Assessment Report: Firazyr, INN-Icatibant. https://www.ema.europa.eu/en/documents/variation-report/firazyr-h-c-899-ii-0024-g-epar-assessment-report-variation_en.pdf.

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