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

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journal contribution
posted on 2024-02-27, 10:01 authored by 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 PB Thomas, Nigel D Hart, Philip Evans, Monique Andersson, Gail Hayward, Kerenza Hood, Jonathan S Nguyen-Van-Tam, Paul Little, FD Richard Hobbs, Saye Khoo, Christopher Butler, David M Lowe, Judith Breuer, PANORAMIC Virology Group
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.


Crick (Grant ID: CC2129, Grant title: Blackman CC2129)