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

Standing, Joseph F., Buggiotti, Laura, Guerra-Assuncao, Jose Afonso, Woodall, Maximillian, Ellis, Samuel, Agyeman, Akosua A., Miller, Charles, Okechukwu, Mercy, Kirkpatrick, Emily, Jacobs, Amy I., Williams, Charlotte A., Roy, Sunando, Martin-Bernal, Luz M., Williams, Rachel, Smith, Claire M., Sanderson, Theo, Ashford, Fiona B., Emmanuel, Beena, Afzal, Zaheer M., Shields, Adrian, Richter, Alex G., Dorward, Jienchi, Gbinigie, Oghenekome, Van Hecke, Oliver, Lown, Mark, Francis, Nick, Jani, Bhautesh, Richards, Duncan B., Rahman, Najib M., Yu, Ly-Mee, Thomas, Nicholas P. B., Hart, Nigel D., Evans, Philip, Andersson, Monique, Hayward, Gail, Hood, Kerenza ORCID: https://orcid.org/0000-0002-5268-8631, Nguyen-Van-Tam, Jonathan S., Little, Paul, Hobbs, F. D. Richard, Khoo, Saye, Butler, Christopher ORCID: https://orcid.org/0000-0002-0102-3453, Lowe, David M. and Breuer, Judith 2024. Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients. Nature Communications 15 (1) , 1652. 10.1038/s41467-024-45641-0

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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

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	26 February 2024
Date of Acceptance:	26 January 2024
Last Modified:	26 Feb 2024 16:15
URI:	https://orca.cardiff.ac.uk/id/eprint/166557

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