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Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients

Author

Listed:
  • Joseph F. Standing

    (University College London
    Great Ormond Street Hospital for Children NHS Trust)

  • Laura Buggiotti

    (University College London)

  • Jose Afonso Guerra-Assuncao

    (University College London)

  • Maximillian Woodall

    (University College London)

  • Samuel Ellis

    (University College London)

  • Akosua A. Agyeman

    (University College London)

  • Charles Miller

    (Great Ormond Street Hospital for Children NHS Trust)

  • Mercy Okechukwu

    (University College London)

  • Emily Kirkpatrick

    (University College London)

  • Amy I. Jacobs

    (University College London)

  • Charlotte A. Williams

    (University College London)

  • Sunando Roy

    (University College London)

  • Luz M. Martin-Bernal

    (University College London)

  • Rachel Williams

    (University College London)

  • Claire M. Smith

    (University College London)

  • Theo Sanderson

    (Francis Crick Institute)

  • Fiona B. Ashford

    (University of Birmingham)

  • Beena Emmanuel

    (University of Birmingham)

  • Zaheer M. Afzal

    (University of Birmingham)

  • Adrian Shields

    (University of Birmingham)

  • Alex G. Richter

    (University of Birmingham)

  • Jienchi Dorward

    (University of Oxford
    University of KwaZulu–Natal)

  • Oghenekome Gbinigie

    (University of Oxford)

  • Oliver Hecke

    (University of Oxford)

  • Mark Lown

    (University of Southampton)

  • Nick Francis

    (University of Southampton)

  • Bhautesh Jani

    (University of Glasgow)

  • Duncan B. Richards

    (University of Oxford)

  • Najib M. Rahman

    (University of Oxford)

  • Ly-Mee Yu

    (University of Oxford)

  • Nicholas P. B. Thomas

    (Windrush Medical Practice)

  • Nigel D. Hart

    (Dentistry and Biomedical Sciences. Queen’s University Belfast)

  • Philip Evans

    (University of Exeter Medical School
    University of Leeds)

  • Monique Andersson

    (Radcliffe Department of Medicine, University of Oxford)

  • Gail Hayward

    (University of Oxford)

  • Kerenza Hood

    (Centre for Trials Research)

  • Jonathan S. Nguyen-Van-Tam

    (University of Nottingham School of Medicine)

  • Paul Little

    (University of Southampton)

  • F. D. Richard Hobbs

    (University of Oxford)

  • Saye Khoo

    (University of Liverpool and Liverpool University Hospitals NHS Foundation Trust)

  • Christopher Butler

    (University of Oxford)

  • David M. Lowe

    (Royal Free London NHS Foundation Trust
    University College London)

  • Judith Breuer

    (University College London
    Great Ormond Street Hospital for Children NHS Trust)

Abstract

Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031

Suggested Citation

  • Joseph F. Standing & Laura Buggiotti & Jose Afonso Guerra-Assuncao & Maximillian Woodall & Samuel Ellis & Akosua A. Agyeman & Charles Miller & Mercy Okechukwu & Emily Kirkpatrick & Amy I. Jacobs & Cha, 2024. "Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45641-0
    DOI: 10.1038/s41467-024-45641-0
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    References listed on IDEAS

    as
    1. Jia Wei & Philippa C. Matthews & Nicole Stoesser & Thomas Maddox & Luke Lorenzi & Ruth Studley & John I. Bell & John N. Newton & Jeremy Farrar & Ian Diamond & Emma Rourke & Alison Howarth & Brian D. M, 2021. "Anti-spike antibody response to natural SARS-CoV-2 infection in the general population," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Timothy P. Sheahan & Amy C. Sims & Sarah R. Leist & Alexandra Schäfer & John Won & Ariane J. Brown & Stephanie A. Montgomery & Alison Hogg & Darius Babusis & Michael O. Clarke & Jamie E. Spahn & Laura, 2020. "Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    3. Theo Sanderson & Ryan Hisner & I’ah Donovan-Banfield & Hassan Hartman & Alessandra Løchen & Thomas P. Peacock & Christopher Ruis, 2023. "A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes," Nature, Nature, vol. 623(7987), pages 594-600, November.
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