Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
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.
Adult, Antibodies, Viral, Antibody Formation, Antiviral Agents/therapeutic use, COVID-19, Cytidine/analogs & derivatives, Humans, Hydroxylamines, Outpatients, SARS-CoV-2/genetics
Standing, Joseph F
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Buggiotti, Laura
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Guerra-Assuncao, Jose Afonso
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Williams, Charlotte A.
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Smith, Claire M.
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Lown, Mark
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Francis, Nick
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Evans, Philip
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Little, Paul
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23 February 2024
Standing, Joseph F
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Buggiotti, Laura
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Guerra-Assuncao, Jose Afonso
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Williams, Charlotte A.
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Smith, Claire M.
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Lown, Mark
4742d5f8-bcf3-4e0b-811c-920e7d010c9b
Francis, Nick
9b610883-605c-4fee-871d-defaa86ccf8e
Evans, Philip
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Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Standing, Joseph F, Buggiotti, Laura and Guerra-Assuncao, Jose Afonso
,
et al. and PANORAMIC Virology Group
(2024)
Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients.
Nature Communications, 15 (1), [1652].
(doi:10.1038/s41467-024-45641-0).
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.
Text
s41467-024-45641-0
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Accepted/In Press date: 26 January 2024
Published date: 23 February 2024
Additional Information:
Publisher Copyright:
© The Author(s) 2024.
Keywords:
Adult, Antibodies, Viral, Antibody Formation, Antiviral Agents/therapeutic use, COVID-19, Cytidine/analogs & derivatives, Humans, Hydroxylamines, Outpatients, SARS-CoV-2/genetics
Identifiers
Local EPrints ID: 487929
URI: http://eprints.soton.ac.uk/id/eprint/487929
ISSN: 2041-1723
PURE UUID: d1742ac8-6fb8-432c-bd92-91c12a8d0bb0
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Date deposited: 11 Mar 2024 17:33
Last modified: 12 Jul 2024 02:05
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Contributors
Author:
Joseph F Standing
Author:
Laura Buggiotti
Author:
Jose Afonso Guerra-Assuncao
Author:
Charlotte A. Williams
Author:
Claire M. Smith
Author:
Philip Evans
Corporate Author: et al.
Corporate Author: PANORAMIC Virology Group
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