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

Adult Humans SARS-CoV-2 / genetics COVID-19 Outpatients Antibody Formation Antibodies, Viral Antiviral Agents / therapeutic use Cytidine / analogs & derivatives Hydroxylamines

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
23 Feb 2024
Historique:
received: 04 08 2023
accepted: 26 01 2024
medline: 26 2 2024
pubmed: 24 2 2024
entrez: 23 2 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-45641-0 PMID: 38396069 PMC: PMC10891158
pubmed: 38396069
doi: 10.1038/s41467-024-45641-0
pii: 10.1038/s41467-024-45641-0
pmc: PMC10891158
doi:

Substances chimiques

molnupiravir YA84KI1VEW
Antibodies, Viral 0
Antiviral Agents 0
Cytidine 5CSZ8459RP
Hydroxylamines 0

Types de publication

Randomized Controlled Trial Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1652

Subventions

Organisme : Medical Research Council
ID : MR/W015560/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001128
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M008665/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600475
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210918/Z/18/Z
Pays : United Kingdom
Organisme : Marie Curie
ID : MCCC-RP-14-A17178
Pays : United Kingdom

Investigateurs

Julie Allen (J)
Nadua Bayzid (N)
Julianne Brown (J)
Doug Burns (D)
Elizabeth Hadley (E)
Jim Hatcher (J)
Tim McHugh (T)
Chris Thalasselis (C)
Mia Tomlinson (M)
Francis Yongblah (F)

Informations de copyright

© 2024. The Author(s).

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Auteurs

Joseph F Standing (JF)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK. j.standing@ucl.ac.uk.
Great Ormond Street Hospital for Children NHS Trust, London, UK. j.standing@ucl.ac.uk.
ORCID: 0000-0002-4561-7173

Laura Buggiotti (L)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.
ORCID: 0000-0002-7404-7800

Jose Afonso Guerra-Assuncao (JA)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Maximillian Woodall (M)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Samuel Ellis (S)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Akosua A Agyeman (AA)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Charles Miller (C)

Great Ormond Street Hospital for Children NHS Trust, London, UK.

Mercy Okechukwu (M)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Emily Kirkpatrick (E)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Amy I Jacobs (AI)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Charlotte A Williams (CA)

Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London, UK.

Sunando Roy (S)

Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London, UK.

Luz M Martin-Bernal (LM)

Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London, UK.

Rachel Williams (R)

Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London, UK.

Claire M Smith (CM)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.
ORCID: 0000-0002-8913-0009

Theo Sanderson (T)

Francis Crick Institute, London, UK.
ORCID: 0000-0003-4177-2851

Fiona B Ashford (FB)

Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
ORCID: 0000-0002-2946-3864

Beena Emmanuel (B)

Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

Zaheer M Afzal (ZM)

Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

Adrian Shields (A)

Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
ORCID: 0000-0001-5345-2156

Alex G Richter (AG)

Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

Jienchi Dorward (J)

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
ORCID: 0000-0001-6072-1430

Oghenekome Gbinigie (O)

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Oliver Van Hecke (O)

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Mark Lown (M)

Primary Care Research Centre, University of Southampton, Southampton, UK.

Nick Francis (N)

Primary Care Research Centre, University of Southampton, Southampton, UK.

Bhautesh Jani (B)

School of Health and Wellbeing, University of Glasgow, Glasgow, UK.

Duncan B Richards (DB)

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
ORCID: 0000-0002-8093-7084

Najib M Rahman (NM)

Respiratory Trials Unit and Oxford NIHR Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
ORCID: 0000-0003-1195-1680

Ly-Mee Yu (LM)

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
ORCID: 0000-0003-0331-7364

Nicholas P B Thomas (NPB)

Windrush Medical Practice, Witney, UK.

Nigel D Hart (ND)

School of Medicine, Dentistry and Biomedical Sciences. Queen's University Belfast, Belfast, UK.
ORCID: 0000-0002-8168-1746

Philip Evans (P)

APEx (Exeter Collaboration for Academic Primary Care), University of Exeter Medical School, Exeter, UK.
National Institute of Health and Care Research, Clinical Research Network, University of Leeds, Leeds, UK.
ORCID: 0000-0002-5277-3545

Monique Andersson (M)

Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
ORCID: 0000-0003-0619-1074

Gail Hayward (G)

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Kerenza Hood (K)

Centre for Trials Research, Cardiff University, Wales, UK.
ORCID: 0000-0002-5268-8631

Jonathan S Nguyen-Van-Tam (JS)

Lifespan and Population Health, University of Nottingham School of Medicine, Nottingham, UK.
ORCID: 0000-0003-2579-4655

Paul Little (P)

Primary Care Research Centre, University of Southampton, Southampton, UK.

F D Richard Hobbs (FDR)

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Saye Khoo (S)

Department of Pharmacology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
ORCID: 0000-0002-2769-0967

Christopher Butler (C)

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
ORCID: 0000-0002-0102-3453

David M Lowe (DM)

Department of Clinical Immunology, Royal Free London NHS Foundation Trust, London, UK.
Institute of Immunity and Transplantation, University College London, London, UK.
ORCID: 0000-0001-6102-2375

Judith Breuer (J)

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.
Great Ormond Street Hospital for Children NHS Trust, London, UK.
ORCID: 0000-0001-8246-0534

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Personnes › Patients › Patients en consultation externe › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité active › Production d'anticorps › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Ribonucléosides › Cytidine › Randomized controlled trial of molnupiravir...
questionsmedicales.fr › Composés chimiques organiques › Amines › Hydroxylamines › Randomized controlled trial of molnupiravir...