Evidence map›Paper›PMID 32962996›Full record

ArticleRespiratory care2021

A Treatment to Eliminate SARS-CoV-2 Replication in Human Airway Epithelial Cells Is Safe for Inhalation as an Aerosol in Healthy Human Subjects.

Michael D Davis, Tatiana M Clemente, Olivia K Giddings, Kristie Ross, Rebekah S Cunningham, Laura Smith, Edward Simpson, Yunlong Liu, Kirsten Kloepfer, I Scott Ramsey and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Respiratory care, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Benefits of Airway Androgen Receptor Expression in Human Asthma.American journal of respiratory and critical care medicine · 2021
    Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

Michael D DavisHerman B. Wells Center for Pediatric Research, Indiana University School of Medicine.
Tatiana M ClementeDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.
Olivia K GiddingsDepartment of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio.
Kristie RossDepartment of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio.
Rebekah S CunninghamHerman B. Wells Center for Pediatric Research, Indiana University School of Medicine.
Laura SmithHerman B. Wells Center for Pediatric Research, Indiana University School of Medicine.
Edward SimpsonCenter for Computational Biology and Informatics, Indiana University School of Medicine, Indianapolis, Indiana.
Yunlong LiuCenter for Computational Biology and Informatics, Indiana University School of Medicine, Indianapolis, Indiana.
Kirsten KloepferDivision of Pulmonology, Allergy and Sleep Medicine, Riley Hospital for Children, Indianapolis, Indiana.
I Scott RamseyDepartment of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia.
Yi ZhaoDepartment of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.
Christopher M RobinsonDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.
Stacey D GilkDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.
Benjamin GastonHerman B. Wells Center for Pediatric Research, Indiana University School of Medicine. begaston@iu.edu.
Indiana University School of MedicineRiley Hospital for Children · USRainbow Babies & Children's Hospital · USIndiana University – Purdue University Indianapolis · USVirginia Commonwealth University · US

Funding

Project 3 - Personalized cystic fibrosis treatment strategies with synergistic therapies Identified in vitro.P01HL128192 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI GASTON, BENJAMIN · 2016 to 2020
$12.2M
S-nitrosylation signaling in asthmaP01HL158507 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI LAHM, TIM · 2021 to 2025
$12.0M
Upper Airway Microbial Development During the First Year of LifeK23AI135094 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI KLOEPFER, KIRSTEN M · 2018 to 2022
$915k
NHLBI NIH HHS P01 HL128192NHLBI NIH HHS P01 HL158507NIAID NIH HHS K23 AI135094NIAID NIH HHS L40 AI096442
6 · The paper itself

Abstract

backgroundLow airway surface pH is associated with many airway diseases, impairs antimicrobial host defense, and worsens airway inflammation. Inhaled Optate is designed to safely raise airway surface pH and is well tolerated in humans. Raising intracellular pH partially prevents activation of SARS-CoV-2 in primary normal human airway epithelial (NHAE) cells, decreasing viral replication by several mechanisms.

methodsWe grew primary NHAE cells from healthy subjects, infected them with SARS-CoV-2 (isolate USA-WA1/2020), and used clinical Optate at concentrations used in humans in vivo to determine whether Optate would prevent viral infection and replication. Cells were pretreated with Optate or placebo prior to infection (multiplicity of infection = 1), and viral replication was determined with plaque assay and nucleocapsid (N) protein levels. Healthy human subjects also inhaled Optate as part of a Phase 2a safety trial.

resultsOptate almost completely prevented viral replication at each time point between 24 h and 120 h, relative to placebo, on both plaque assay and N protein expression (

conclusionsInhaled Optate may be well suited for a clinical trial in patients with pulmonary SARS-CoV-2 infection. However, it is vitally important for patient safety that formulations designed for inhalation with regard to pH, isotonicity, and osmolality be used. An inhalational treatment that safely prevents SARS-CoV-2 viral replication could be helpful for treating patients with pulmonary SARS-CoV-2 infection.

Indexed as

COVID-19 Drug TreatmentSARS-CoV-2Administration, InhalationAntiviral AgentsCells, CulturedEpithelial CellsGlycineHealthy VolunteersHumansHydrogen-Ion ConcentrationIsotonic SolutionsLungVirus ReplicationAntiviral AgentsGlycineIsotonic SolutionsOptateairway pHCOVID-19SARS-CoV-2

Identifiers

PMID32962996
PMCPMC7856523
OpenAlexW3087482805

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.