Evidence map›Paper›PMID 39247686›Full record

ArticlePathogens & immunity2024

Impact of SARS-CoV-2 Resistance to Antiviral Monoclonal Antibody Therapy on Neutralizing Antibody Response.

Marc-Kendy Paul, Manish C Choudhary, Amy L Heaps, Rinki Deo, Daniela Moisi, Kelley C Gordon, John W Mellors, Carlee Moser, Paul Klekotka, Alan Landay and 8 more

Registry-linked trialAbstract read
In one paragraph

Article in Pathogens & immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04518410 (Adaptive Platform Treatment Trial for Outpatients With COVID-19), which is not on this 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.

NCT04518410 phase2 / phase3completednot on this map

Adaptive Platform Treatment Trial for Outpatients With COVID-19 (Adapt Out COVID)

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2020 to 2023Enrolled4,044ConditionsCoronavirus, Covid19Armsbamlanivimab 7000mg, BRII-196+BRII-198, AZD7442 (IV), AZD7442 (IM), SNG001
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. 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

18 authors.

Marc-Kendy PaulBrigham and Women's Hospital, Harvard Medical School, Cambridge, MA.
Manish C ChoudharyBrigham and Women's Hospital, Harvard Medical School, Cambridge, MA.
Amy L HeapsUniversity of Pittsburgh School of Medicine, Pittsburgh, PA.
Rinki DeoBrigham and Women's Hospital, Harvard Medical School, Cambridge, MA.
Daniela MoisiCase Western Reserve University, Cleveland, OH.
Kelley C GordonUniversity of Pittsburgh School of Medicine, Pittsburgh, PA.
John W MellorsUniversity of Pittsburgh School of Medicine, Pittsburgh, PA.
Carlee MoserHarvard T.H. Chan School of Public Health, Boston, MA.
Paul KlekotkaEli Lilly and Company, San Diego, CA.
Alan LandayRUSH Medical College, Chicago, IL.
Judith S CurrierDavid Geffen School of Medicine, University of California, Los Angeles, CA.
Joseph J EronUniversity of North Carolina at Chapel Hill, Chapel Hill, NC.
Kara W ChewDavid Geffen School of Medicine, University of California, Los Angeles, CA.
Davey M SmithUniversity of California, San Diego, CA.
Scott F SiegCase Western Reserve University and University Hospitals Cleveland, Cleveland, OH.
Urvi M ParikhUniversity of Pittsburgh School of Medicine, Pittsburgh, PA.
Jonathan Z LiBrigham and Women's Hospital, Harvard Medical School, Cambridge, MA.
ACTIV-2/A5401 Study Team

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026
$71.8M
Harvard Medical School Vaccine Clinical Trials UnitUM1AI069412 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Lindsey Robert Baden, Daniel R. Kuritzkes · 2012 to 2026
$57.2M
UCLA AIDS Prevention and Treatment Clinical Trials UnitUM1AI069424 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Judith S. Currier, RAPHAEL J LANDOVITZ · 2012 to 2026
$51.8M
University of Pittsburgh Clinical Trials UnitUM1AI069494 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SUSAN L KOLETAR, John W Mellors · 2012 to 2026
$38.0M
Wits HIV Research Group CLINICAL TRIAL UNIT (CTU) reapplicationUM1AI069463 · NIAID · WITS HEALTH CONSORTIUM (PTY), LTD · PI REES, HELEN, SANNE, IAN MATTHIAS · 2012 to 2025
$31.8M
Units for HIV/AIDS Clinical Trials NetworksU01AI069463 · NIAID · WITS HEALTH CONSORTIUM (PTY), LTD · PI SANNE, IAN MATTHIAS · 2007 to 2011
$24.2M
NIAID NIH HHS U01 AI068636NIAID NIH HHS U01 AI069463NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069412NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI069424NIAID NIH HHS UM1 AI069463NIAID NIH HHS UM1 AI069494
6 · The paper itself

Abstract

Background: Anti-SARS-CoV-2 monoclonal antibodies (mAbs) have played a key role as an anti-viral against SARS-CoV-2, but there is a potential for resistance to develop. The interplay between host antibody responses and the development of monoclonal antibody (mAb) resistance is a critical area of investigation. In this study, we assessed host neutralizing antibody (nAb) responses against both ancestral virus and those with treatment-emergent E484K bamlanivimab resistance mutations. Methods: Study participants were enrolled in the ACTIV-2/Advancing Clinical Therapeutics Globally (ACTG) A5401 phase 2 randomized, placebo-controlled trial of bamlanivimab 700 mg mAb therapy (NCT04518410). Anterior nasal and nasopharyngeal swabs were collected for SARS-CoV-2 RNA testing and S gene next-generation sequencing to identify the E484K bamlanivimab resistance mutation. Serum nAb titers were assessed by pseudovirus neutralization assays. Results: Higher baseline (pre-treatment) nAb titers against either ancestral or E484K virus was associated with lower baseline viral load. Participants with emerging resistance had low levels of nAb titers against either ancestral or E484K nAb at the time of study entry. Participants with emergent E484K resistance developed significantly higher levels of E484K-specific nAb titers compared to mAb-treated individuals who did not develop resistance. All participants who developed the E484K mAb resistance mutation were eventually able to clear the virus. Conclusion: Emerging drug resistance after SARS-CoV-2-specific mAb therapy led to a heightened host neutralizing antibody response to the mAb-resistant variant that was associated with eventual viral clearance. This demonstrates the interplay between the antiviral treatment-directed viral evolution and subsequent host immune response in viral clearance.

Indexed as

bamlanivimabCOVID-19monoclonal antibodypseudovirus neutralizationSARS-CoV-2

Identifiers

PMID39247686
PMCPMC11378757

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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.