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Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach.

Publication ,  Journal Article
Kuebler, WM; Jordt, S-E; Liedtke, WB
Published in: Am J Physiol Lung Cell Mol Physiol
June 1, 2020

Lethality of coronavirus disease (COVID-19) during the 2020 pandemic, currently still in the exponentially accelerating phase in most countries, is critically driven by disruption of the alveolo-capillary barrier of the lung, leading to lung edema as a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We argue for inhibition of the transient receptor potential vanilloid 4 (TRPV4) calcium-permeable ion channel as a strategy to address this issue, based on the rationale that TRPV4 inhibition is protective in various preclinical models of lung edema and that TRPV4 hyperactivation potently damages the alveolo-capillary barrier, with lethal outcome. We believe that TRPV4 inhibition has a powerful prospect at protecting this vital barrier in COVID-19 patients, even to rescue a damaged barrier. A clinical trial using a selective TRPV4 inhibitor demonstrated a benign safety profile in healthy volunteers and in patients suffering from cardiogenic lung edema. We argue for expeditious clinical testing of this inhibitor in COVID-19 patients with respiratory malfunction and at risk for lung edema. Perplexingly, among the currently pursued therapeutic strategies against COVID-19, none is designed to directly protect the alveolo-capillary barrier. Successful protection of the alveolo-capillary barrier will not only reduce COVID-19 lethality but will also preempt a distressing healthcare scenario with insufficient capacity to provide ventilator-assisted respiration.

Duke Scholars

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Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

June 1, 2020

Volume

318

Issue

6

Start / End Page

L1239 / L1243

Location

United States

Related Subject Headings

  • TRPV Cation Channels
  • SARS-CoV-2
  • Respiratory System
  • Respiration, Artificial
  • Pulmonary Edema
  • Pneumonia, Viral
  • Pandemics
  • Lung
  • Humans
  • Coronavirus Infections
 

Citation

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Chicago
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MLA
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Kuebler, W. M., Jordt, S.-E., & Liedtke, W. B. (2020). Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach. Am J Physiol Lung Cell Mol Physiol, 318(6), L1239–L1243. https://doi.org/10.1152/ajplung.00161.2020
Kuebler, Wolfgang M., Sven-Eric Jordt, and Wolfgang B. Liedtke. “Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach.Am J Physiol Lung Cell Mol Physiol 318, no. 6 (June 1, 2020): L1239–43. https://doi.org/10.1152/ajplung.00161.2020.
Kuebler WM, Jordt S-E, Liedtke WB. Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach. Am J Physiol Lung Cell Mol Physiol. 2020 Jun 1;318(6):L1239–43.
Kuebler, Wolfgang M., et al. “Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach.Am J Physiol Lung Cell Mol Physiol, vol. 318, no. 6, June 2020, pp. L1239–43. Pubmed, doi:10.1152/ajplung.00161.2020.
Kuebler WM, Jordt S-E, Liedtke WB. Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach. Am J Physiol Lung Cell Mol Physiol. 2020 Jun 1;318(6):L1239–L1243.

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

June 1, 2020

Volume

318

Issue

6

Start / End Page

L1239 / L1243

Location

United States

Related Subject Headings

  • TRPV Cation Channels
  • SARS-CoV-2
  • Respiratory System
  • Respiration, Artificial
  • Pulmonary Edema
  • Pneumonia, Viral
  • Pandemics
  • Lung
  • Humans
  • Coronavirus Infections