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

Standing, J. F. et al. (2024) Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients. Nature Communications, 15, 1652. (doi: 10.1038/s41467-024-45641-0) (PMID:38396069) (PMCID:PMC10891158)

Abstract

Viral clearance, antibody response and the mutagenic effect of molnupiravir has not 77 been elucidated in at-risk populations. Non-hospitalised participants within 5 days of 78 SARS-CoV-2 symptoms randomised to receive molnupiravir (n=253) or Usual Care 79 (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.

• Item Type: Articles
• Additional Information: This study was funded by the UK NIHR (NIHR135366) to C.B. and its design and analysis methods supported by a grant from the UK MRC (MR/X004724/1) to J.F.S. The funders had no role in designing the study.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jani, Dr Bhautesh
• Authors: Standing, J. F., Buggiotti, L., Guerra-Assuncao, J. A., Woodall, M., Ellis, S., Agyeman, A. A., Miller, C., Okechukwu, M., Kirkpatrick, E., Jacobs, A. I., Williams, C. A., Roy, S., Martin-Bernal, L. M., Williams, R., Smith, C. M., Sanderson, T., Ashford, F., Emmanuel, B., Afzal, Z. M., Sheilds, A., Richter, A., Dorward, J., Gbinigie, O., Van Hecke, O., Lown, M., Francis, N., Jani, B., Richards, D. B., Rahman, N. M., Yu, L.-M., Thomas, N. P.B., Hart, N. D., Evans, P., Andersson, M., Hayward, G., Hood, K., Nguyen-Van-Tam, J. S., Little, P., Hobbs, F.D. R., Khoo, S., Butler, C., Lowe, D. M., Breuer, J., and PANORAMIC Virology Group,
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright: © The Author(s) 2024
• First Published: First published in Nature Communications 15: 1652
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
316049		Platform Adaptive trial of NOvel antiviRals for eArly treatMent of COVID-19 In the Community (PANORAMIC)	Bhautesh Jani	National Institute for Health Research (NIHR)	BZR04240 NIHR135366	SHW - General Practice & Primary Care