Evidence map›Paper›PMID 39012120›Full record

ArticleMicrobiology spectrum2024

Ronapreve (REGN-CoV; casirivimab and imdevimab) reduces the viral burden and alters the pulmonary response to the SARS-CoV-2 Delta variant (B.1.617.2) in K18-hACE2 mice using an experimental design reflective of a treatment use case.

Lee Tatham, Anja Kipar, Jo Sharp, Edyta Kijak, Joanne Herriott, Megan Neary, Helen Box, Eduardo Gallardo Toledo, Anthony Valentijn, Helen Cox and 7 more

Abstract read
In one paragraph

Article in Microbiology spectrum, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Lee Tatham *Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0001-9448-8876
Anja Kipar *Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-7289-3459
Jo SharpDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Edyta KijakDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Joanne HerriottDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Megan NearyDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Helen BoxDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Eduardo Gallardo ToledoDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Anthony ValentijnDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Helen CoxDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Henry PertinezDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Paul CurleyDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Usman ArshadDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Rajith Kumar Reddy RajoliDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0002-6015-5712
Steve RannardCentre of Excellence in Long-acting Therapeutics (CELT), University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0002-6946-1097
James P StewartDepartment of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Andrew OwenDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0002-9819-7651

Funding

The Long-Acting/Extended Release Antiretroviral Resource Program (LEAP)R24AI118397 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Charles W. Flexner · 2015 to 2026
$9.4M
Long acting NRTI therapies for HIVR01AI134091 · NIAID · JOHNS HOPKINS UNIVERSITY · PI FREEL MEYERS, CAREN L., RANNARD, STEVE · 2017 to 2021
$3.1M
European Union & Horizon Europe research and innovation program 101057553HHS | National Institutes of Health (NIH) R01AI134091, R24AI118397NIAID NIH HHS R01 AI134091NIAID NIH HHS R24 AI118397Swiss National Science Foundation (SNSF) IZSEZ0, 213289Swiss State Secretariat for Education, Research and Innovation (SERI) 22.00094UKRI | Biotechnology and Biological Sciences Research Council (BBSRC) BB/R00904X/1, BB/R018863/1, BB/N022505/1UKRI | Engineering and Physical Sciences Research Council (EPSRC) EP/R024804/1, EP/S012265/1UKRI | Innovate UK TS/V012967/1UKRI | Medical Research Council (MRC) MR/W005611/1, MR/R010145/1Unitaid LONGEVITYWellcome TrustWellcome Trust (WT) 222489/Z/21/Z
6 · The paper itself

Abstract

With some exceptions, global policymakers have recommended against the use of existing monoclonal antibodies in COVID-19 due to loss of neutralization of newer variants. The purpose of this study was to investigate the impact of Ronapreve on compartmental viral replication using paradigms for susceptible and insusceptible variants. Virological efficacy and impact on pathogenicity was assessed in K18-hACE2 mice inoculated with either the Delta or BA.1 Omicron variants. Ronapreve reduced sub-genomic viral RNA levels in lung and nasal turbinate, 4 and 6 days post-infection, for the Delta variant but not the Omicron variant. It also blocked brain infection, which is seen with high frequency in K18-hACE2 mice after Delta variant infection. At day 6, the inflammatory response to lung infection with the Delta variant was altered to a multifocal granulomatous inflammation in which the virus appeared to be confined. The current study provides evidence of an altered tissue response to SARS-CoV-2 after treatment with a monoclonal antibody combination that retains neutralization activity. These data demonstrate that experimental designs that reflect treatment use cases are achievable in animal models for monoclonal antibodies. Extreme caution should be taken when interpreting prophylactic experimental designs that may not be representative of treatment.IMPORTANCEFollowing the emergence of the SARS-CoV-2 Omicron variant, the WHO recommended against the use of Ronapreve in its COVID-19 treatment guidelines due to a lack of efficacy based on current pharmacokinetic-pharmacodynamic understanding. However, the continued use of Ronapreve, specifically in vulnerable patients, was advocated by some based on

Indexed as

Antibodies, NeutralizingCOVID-19COVID-19 Drug TreatmentLungSARS-CoV-2Angiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, ViralAntiviral AgentsDisease Models, AnimalFemaleHumansMiceViral LoadACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntibodies, ViralAntiviral AgentsmAbpreclinical PK/PDSARS-CoV-2

Identifiers

PMID39012120
PMCPMC11302283

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Registered trials

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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.