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. doi: 10.1152/ajplung.00161.2020. Epub 2020 May 13.


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.

Keywords: COVID-19; SARS-CoV-2; TRPV4; TRPV4 inhibitor; pulmonary edema.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betacoronavirus*
  • COVID-19
  • Calcium / metabolism
  • Coronavirus Infections* / virology
  • Humans
  • Lung / metabolism
  • Lung / virology*
  • Pandemics*
  • Pneumonia, Viral* / virology
  • Pulmonary Edema / prevention & control*
  • Pulmonary Edema / virology
  • Respiration, Artificial
  • SARS-CoV-2
  • TRPV Cation Channels / antagonists & inhibitors*


  • TRPV Cation Channels
  • TRPV4 protein, human
  • Calcium