ArticleAmerican journal of physiology. Lung cellular and molecular physiology2020
Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach.
Article in American journal of physiology. Lung cellular and molecular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05304702 (Lung Injury), which is not on this map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Lung Injury (Pulmonary Edema) in COVID-19: Treatment With Furosemide and Negative Fluid Balance (NEGBAL): a Case-Control Study
Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- Transient receptor potential channels in viral infectious diseases: Biological characteristics and regulatory mechanisms.Journal of advanced research · 2025Review
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- Recent advances on the structure and the function relationships of the TRPV4 ion channel.Channels (Austin, Tex.) · 2024Review
- TRPV4-A Multifunctional Cellular Sensor Protein with Therapeutic Potential.Sensors (Basel, Switzerland) · 2024Review
- Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients.Function (Oxford, England) · 2024Article
- The endothelium: gatekeeper to lung ischemia-reperfusion injury.Respiratory research · 2024Review
- Effect of TRPV4 Antagonist GSK2798745 on Chlorine Gas-Induced Acute Lung Injury in a Swine Model.International journal of molecular sciences · 2024Article
- TRP Ion Channels in Immune Cells and Their Implications for Inflammation.International journal of molecular sciences · 2024Review
- SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells.Signal transduction and targeted therapy · 2023Article
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- Interaction of Teleost Fish TRPV4 with DEAD Box RNA Helicase 1 Regulates Iridovirus Replication.Journal of virology · 2023Article
- Unconventional interactions of the TRPV4 ion channel with beta-adrenergic receptor ligands.Life science alliance · 2023Article
- Microplastics: A Real Global Threat for Environment and Food Safety: A State of the Art Review.Nutrients · 2023Review
- Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer.Oncology research · 2023Article
- Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms.Frontiers in molecular neuroscience · 2023Review
- ARDS in the time of corona: context and perspective.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Review
- Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome.Journal of advanced research · 2022Review
- Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion.eLife · 2022Article
- Calcium-Permeable Channels and Endothelial Dysfunction in Acute Lung Injury.Current issues in molecular biology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.