Nature Communications (Feb 2024)
Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
- 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,
- Charlotte A. Williams,
- Sunando Roy,
- Luz M. Martin-Bernal,
- Rachel Williams,
- Claire M. Smith,
- Theo Sanderson,
- Fiona B. Ashford,
- Beena Emmanuel,
- Zaheer M. Afzal,
- Adrian Shields,
- Alex G. Richter,
- Jienchi Dorward,
- Oghenekome Gbinigie,
- Oliver Van Hecke,
- Mark Lown,
- Nick Francis,
- Bhautesh Jani,
- Duncan B. Richards,
- Najib M. Rahman,
- Ly-Mee Yu,
- Nicholas P. B. Thomas,
- Nigel D. Hart,
- Philip Evans,
- Monique Andersson,
- Gail Hayward,
- Kerenza Hood,
- Jonathan S. Nguyen-Van-Tam,
- Paul Little,
- F. D. Richard Hobbs,
- Saye Khoo,
- Christopher Butler,
- David M. Lowe,
- Judith Breuer,
- PANORAMIC Virology Group
Affiliations
- Joseph F. Standing
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Laura Buggiotti
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Jose Afonso Guerra-Assuncao
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Maximillian Woodall
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Samuel Ellis
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Akosua A. Agyeman
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Charles Miller
- Great Ormond Street Hospital for Children NHS Trust
- Mercy Okechukwu
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Emily Kirkpatrick
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Amy I. Jacobs
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Charlotte A. Williams
- Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London
- Sunando Roy
- Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London
- Luz M. Martin-Bernal
- Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London
- Rachel Williams
- Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London
- Claire M. Smith
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- Theo Sanderson
- Francis Crick Institute
- Fiona B. Ashford
- Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham
- Beena Emmanuel
- Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham
- Zaheer M. Afzal
- Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham
- Adrian Shields
- Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham
- Alex G. Richter
- Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham
- Jienchi Dorward
- Nuffield Department of Primary Care Health Sciences, University of Oxford
- Oghenekome Gbinigie
- Nuffield Department of Primary Care Health Sciences, University of Oxford
- Oliver Van Hecke
- Nuffield Department of Primary Care Health Sciences, University of Oxford
- Mark Lown
- Primary Care Research Centre, University of Southampton
- Nick Francis
- Primary Care Research Centre, University of Southampton
- Bhautesh Jani
- School of Health and Wellbeing, University of Glasgow
- Duncan B. Richards
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford
- Najib M. Rahman
- Respiratory Trials Unit and Oxford NIHR Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford
- Ly-Mee Yu
- Nuffield Department of Primary Care Health Sciences, University of Oxford
- Nicholas P. B. Thomas
- Windrush Medical Practice
- Nigel D. Hart
- School of Medicine, Dentistry and Biomedical Sciences. Queen’s University Belfast
- Philip Evans
- APEx (Exeter Collaboration for Academic Primary Care), University of Exeter Medical School
- Monique Andersson
- Radcliffe Department of Medicine, University of Oxford
- Gail Hayward
- Nuffield Department of Primary Care Health Sciences, University of Oxford
- Kerenza Hood
- Centre for Trials Research
- Jonathan S. Nguyen-Van-Tam
- Lifespan and Population Health, University of Nottingham School of Medicine
- Paul Little
- Primary Care Research Centre, University of Southampton
- F. D. Richard Hobbs
- Nuffield Department of Primary Care Health Sciences, University of Oxford
- Saye Khoo
- Department of Pharmacology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust
- Christopher Butler
- Nuffield Department of Primary Care Health Sciences, University of Oxford
- David M. Lowe
- Department of Clinical Immunology, Royal Free London NHS Foundation Trust
- Judith Breuer
- Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London
- PANORAMIC Virology Group
- DOI
- https://doi.org/10.1038/s41467-024-45641-0
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 14
Abstract
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
