Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
- Radboud University Medical Center, Netherlands
- Radboud University Medical Centre, Netherlands
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
Frank L van de Veerdonk
Funding
No external funding was received for this work.
Reviewing Editor
- Zsolt Molnár, University of Pécs, Medical School, Hungary
Version history
- Received: April 9, 2020
- Accepted: April 26, 2020
- Accepted Manuscript published: April 27, 2020 (version 1)
- 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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Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
eLife 9:e57555.
https://doi.org/10.7554/eLife.57555
Further reading
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- Medicine
- Microbiology and Infectious Disease
- Epidemiology and Global Health
- Immunology and Inflammation
eLife has published articles on a wide range of infectious diseases, including COVID-19, influenza, tuberculosis, HIV/AIDS, malaria and typhoid fever.
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- Medicine
Background:
To systematically identify cell types in the human ligament, investigate how ligamental cell identities, functions, and interactions participated in the process of ligamental degeneration, and explore the changes of ligamental microenvironment homeostasis in the disease progression.
Methods:
Using single-cell RNA sequencing and spatial RNA sequencing of approximately 49,356 cells, we created a comprehensive cell atlas of healthy and degenerated human anterior cruciate ligaments. We explored the variations of the cell subtypes’ spatial distributions and the different processes involved in the disease progression, linked them with the ligamental degeneration process using computational analysis, and verified findings with immunohistochemical and immunofluorescent staining.
Results:
We identified new fibroblast subgroups that contributed to the disease, mapped out their spatial distribution in the tissue and revealed two dynamic trajectories in the process of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways that may contribute to the disease.
Conclusions:
This cell atlas provides the molecular foundation for investigating how ligamental cell identities, biochemical functions, and interactions contributed to the ligamental degeneration process. The discoveries revealed the pathogenesis of ligamental degeneration at the single-cell and spatial level, which is characterized by extracellular matrix remodeling. Our results provide new insights into the control of ligamental degeneration and potential clues to developing novel diagnostic and therapeutic strategies.
Funding:
This study was funded by the National Natural Science Foundation of China (81972123, 82172508, 82372490) and 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301).
