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

  1. Frank L van de Veerdonk  Is a corresponding author
  2. Mihai G Netea
  3. Marcel van Deuren
  4. Jos WM van der Meer
  5. Quirijn de Mast
  6. Roger J Brüggemann
  7. Hans van der Hoeven
  1. Radboud University Medical Center, Netherlands
  2. Radboud University Medical Centre, Netherlands
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Cite this article as: eLife 2020;9:e57555 doi: 10.7554/eLife.57555

Abstract

COVID-19 patients can present with pulmonary edema early in disease. We propose that the 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 RAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Here we hypothesize that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19. We propose that blocking the B2 receptor and inhibiting 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.

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There are no datasets associated with this work.

Article and author information

Author details

  1. Frank L van de Veerdonk

    Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    For correspondence
    frank.vandeveerdonk@radboudumc.nl
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1121-4894
  2. Mihai G Netea

    Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  3. Marcel van Deuren

    Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  4. Jos WM van der Meer

    Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands
    Competing interests
    Jos WM van der Meer, Senior editor, eLife.
  5. Quirijn de Mast

    Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  6. Roger J Brüggemann

    Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  7. Hans van der Hoeven

    Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.

Funding

No external funding was received for this work.

Reviewing Editor

  1. Zsolt Molnár, University of Pécs, Medical School, Hungary

Publication history

  1. Received: April 9, 2020
  2. Accepted: April 26, 2020
  3. Accepted Manuscript published: April 27, 2020 (version 1)
  4. Version of Record published: May 11, 2020 (version 2)

Copyright

© 2020, van de Veerdonk et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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    Funding:

    This work was supported by funding from the Ford Foundation, NEI/NIH, Research to Prevent Blindness, Foundation Fighting Blindness, UPMC Immune Transplant and Therapy Center, and the Van Sloun fund for canine genetic research.