Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
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 a...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45641-0 |
| _version_ | 1797273858817916928 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Joseph F. Standing |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-03-07T14:50:10Z |
| format | Article |
| id | doaj.art-01afce3eddb24d8aa3b7e67fa19987db |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:50:10Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-01afce3eddb24d8aa3b7e67fa19987db2024-03-05T19:43:37ZengNature PortfolioNature Communications2041-17232024-02-0115111410.1038/s41467-024-45641-0Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatientsJoseph F. Standing0Laura Buggiotti1Jose Afonso Guerra-Assuncao2Maximillian Woodall3Samuel Ellis4Akosua A. Agyeman5Charles Miller6Mercy Okechukwu7Emily Kirkpatrick8Amy I. Jacobs9Charlotte A. Williams10Sunando Roy11Luz M. Martin-Bernal12Rachel Williams13Claire M. Smith14Theo Sanderson15Fiona B. Ashford16Beena Emmanuel17Zaheer M. Afzal18Adrian Shields19Alex G. Richter20Jienchi Dorward21Oghenekome Gbinigie22Oliver Van Hecke23Mark Lown24Nick Francis25Bhautesh Jani26Duncan B. Richards27Najib M. Rahman28Ly-Mee Yu29Nicholas P. B. Thomas30Nigel D. Hart31Philip Evans32Monique Andersson33Gail Hayward34Kerenza Hood35Jonathan S. Nguyen-Van-Tam36Paul Little37F. D. Richard Hobbs38Saye Khoo39Christopher Butler40David M. Lowe41Judith Breuer42PANORAMIC Virology GroupInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonGreat Ormond Street Hospital for Children NHS TrustInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College LondonInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonFrancis Crick InstituteClinical Immunology Service, Institute of Immunology and Immunotherapy, University of BirminghamClinical Immunology Service, Institute of Immunology and Immunotherapy, University of BirminghamClinical Immunology Service, Institute of Immunology and Immunotherapy, University of BirminghamClinical Immunology Service, Institute of Immunology and Immunotherapy, University of BirminghamClinical Immunology Service, Institute of Immunology and Immunotherapy, University of BirminghamNuffield Department of Primary Care Health Sciences, University of OxfordNuffield Department of Primary Care Health Sciences, University of OxfordNuffield Department of Primary Care Health Sciences, University of OxfordPrimary Care Research Centre, University of SouthamptonPrimary Care Research Centre, University of SouthamptonSchool of Health and Wellbeing, University of GlasgowNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of OxfordRespiratory Trials Unit and Oxford NIHR Biomedical Research Centre, Nuffield Department of Medicine, University of OxfordNuffield Department of Primary Care Health Sciences, University of OxfordWindrush Medical PracticeSchool of Medicine, Dentistry and Biomedical Sciences. Queen’s University BelfastAPEx (Exeter Collaboration for Academic Primary Care), University of Exeter Medical SchoolRadcliffe Department of Medicine, University of OxfordNuffield Department of Primary Care Health Sciences, University of OxfordCentre for Trials ResearchLifespan and Population Health, University of Nottingham School of MedicinePrimary Care Research Centre, University of SouthamptonNuffield Department of Primary Care Health Sciences, University of OxfordDepartment of Pharmacology, University of Liverpool and Liverpool University Hospitals NHS Foundation TrustNuffield Department of Primary Care Health Sciences, University of OxfordDepartment of Clinical Immunology, Royal Free London NHS Foundation TrustInfection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College LondonAbstract 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: ISRCTN30448031https://doi.org/10.1038/s41467-024-45641-0 |
| spellingShingle | 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 Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients Nature Communications |
| title | Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients |
| title_full | Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients |
| title_fullStr | Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients |
| title_full_unstemmed | Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients |
| title_short | Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients |
| title_sort | randomized controlled trial of molnupiravir sars cov 2 viral and antibody response in at risk adult outpatients |
| url | https://doi.org/10.1038/s41467-024-45641-0 |
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