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

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...

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Autores principales: van de Veerdonk, Frank L, Netea, Mihai G, van Deuren, Marcel, van der Meer, Jos WM, de Mast, Quirijn, Brüggemann, Roger J, van der Hoeven, Hans
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213974/
https://www.ncbi.nlm.nih.gov/pubmed/32338605
http://dx.doi.org/10.7554/eLife.57555
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author van de Veerdonk, Frank L
Netea, Mihai G
van Deuren, Marcel
van der Meer, Jos WM
de Mast, Quirijn
Brüggemann, Roger J
van der Hoeven, Hans
author_facet van de Veerdonk, Frank L
Netea, Mihai G
van Deuren, Marcel
van der Meer, Jos WM
de Mast, Quirijn
Brüggemann, Roger J
van der Hoeven, Hans
author_sort van de Veerdonk, Frank L
collection PubMed
description 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.
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spelling pubmed-72139742020-05-13 Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome van de Veerdonk, Frank L Netea, Mihai G van Deuren, Marcel van der Meer, Jos WM de Mast, Quirijn Brüggemann, Roger J van der Hoeven, Hans eLife Human Biology and Medicine 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. eLife Sciences Publications, Ltd 2020-04-27 /pmc/articles/PMC7213974/ /pubmed/32338605 http://dx.doi.org/10.7554/eLife.57555 Text en © 2020, van de Veerdonk et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Human Biology and Medicine
van de Veerdonk, Frank L
Netea, Mihai G
van Deuren, Marcel
van der Meer, Jos WM
de Mast, Quirijn
Brüggemann, Roger J
van der Hoeven, Hans
Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
title Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
title_full Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
title_fullStr Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
title_full_unstemmed Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
title_short Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
title_sort kallikrein-kinin blockade in patients with covid-19 to prevent acute respiratory distress syndrome
topic Human Biology and Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213974/
https://www.ncbi.nlm.nih.gov/pubmed/32338605
http://dx.doi.org/10.7554/eLife.57555
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