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

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 P B Thomas; Nigel D Hart; Philip Evans; Monique Andersson; Gail Hayward; Kerenza Hood; Jonathan S Nguyen-Van-Tam; Paul Little; F D Richard Hobbs; Saye Khoo; Christopher Butler; David M Lowe; Judith Breuer; PANORAMIC Virology Group

doi:10.1038/s41467-024-45641-0

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

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 ShieldsAlex 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 P B Thomas, Nigel D Hart, Philip Evans, Monique Andersson, Gail Hayward, Kerenza Hood, Jonathan S Nguyen-Van-Tam, Paul Little, F D Richard Hobbs, Saye Khoo, Christopher Butler, David M Lowe, Judith Breuer, PANORAMIC Virology Group

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	1652
Journal	Nature Communications
Volume	15
DOIs	https://doi.org/10.1038/s41467-024-45641-0
Publication status	Published - 23 Feb 2024

Keywords

Humans
Hydroxylamines
Cytidine
Antibodies, Viral
Antiviral Agents
Antibody Formation
Adult
Outpatients
COVID-19
SARS-CoV-2

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Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
Copyright 2024 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 3.23 MBLicence: CC BY

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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. B., Emmanuel, B., Afzal, Z. M., ... PANORAMIC Virology Group (2024). Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients. Nature Communications, 15, Article 1652. https://doi.org/10.1038/s41467-024-45641-0

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

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. ",

keywords = "Humans, Hydroxylamines, Cytidine, Antibodies, Viral, Antiviral Agents, Antibody Formation, Adult, Outpatients, COVID-19, SARS-CoV-2",

author = "Standing, {Joseph F} and Laura Buggiotti and Guerra-Assuncao, {Jose Afonso} and Maximillian Woodall and Samuel Ellis and Agyeman, {Akosua A} and Charles Miller and Mercy Okechukwu and Emily Kirkpatrick and Jacobs, {Amy I} and Williams, {Charlotte A} and Sunando Roy and Martin-Bernal, {Luz M} and Rachel Williams and Smith, {Claire M} and Theo Sanderson and Ashford, {Fiona B} and Beena Emmanuel and Afzal, {Zaheer M} and Adrian Shields and Richter, {Alex G} and Jienchi Dorward and Oghenekome Gbinigie and {Van Hecke}, Oliver and Mark Lown and Nick Francis and Bhautesh Jani and Richards, {Duncan B} and Rahman, {Najib M} and Ly-Mee Yu and Thomas, {Nicholas P B} and Hart, {Nigel D} and Philip Evans and Monique Andersson and Gail Hayward and Kerenza Hood and Nguyen-Van-Tam, {Jonathan S} and Paul Little and Hobbs, {F D Richard} and Saye Khoo and Christopher Butler and Lowe, {David M} and Judith Breuer and {PANORAMIC Virology Group}",

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doi = "10.1038/s41467-024-45641-0",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Standing, JF, Buggiotti, L, Guerra-Assuncao, JA, Woodall, M, Ellis, S, Agyeman, AA, Miller, C, Okechukwu, M, Kirkpatrick, E, Jacobs, AI, Williams, CA, Roy, S, Martin-Bernal, LM, Williams, R, Smith, CM, Sanderson, T, Ashford, FB, Emmanuel, B, Afzal, ZM, Shields, A, Richter, AG, Dorward, J, Gbinigie, O, Van Hecke, O, Lown, M, Francis, N, Jani, B, Richards, DB, Rahman, NM, Yu, L-M, Thomas, NPB, Hart, ND, Evans, P, Andersson, M, Hayward, G, Hood, K, Nguyen-Van-Tam, JS, Little, P, Hobbs, FDR, Khoo, S, Butler, C, Lowe, DM, Breuer, J & PANORAMIC Virology Group 2024, 'Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients', Nature Communications, vol. 15, 1652. https://doi.org/10.1038/s41467-024-45641-0

TY - JOUR

T1 - Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients

AU - Standing, Joseph F

AU - Buggiotti, Laura

AU - Guerra-Assuncao, Jose Afonso

AU - Woodall, Maximillian

AU - Ellis, Samuel

AU - Agyeman, Akosua A

AU - Miller, Charles

AU - Okechukwu, Mercy

AU - Kirkpatrick, Emily

AU - Jacobs, Amy I

AU - Williams, Charlotte A

AU - Roy, Sunando

AU - Martin-Bernal, Luz M

AU - Williams, Rachel

AU - Smith, Claire M

AU - Sanderson, Theo

AU - Ashford, Fiona B

AU - Emmanuel, Beena

AU - Afzal, Zaheer M

AU - Shields, Adrian

AU - Richter, Alex G

AU - Dorward, Jienchi

AU - Gbinigie, Oghenekome

AU - Van Hecke, Oliver

AU - Lown, Mark

AU - Francis, Nick

AU - Jani, Bhautesh

AU - Richards, Duncan B

AU - Rahman, Najib M

AU - Yu, Ly-Mee

AU - Thomas, Nicholas P B

AU - Hart, Nigel D

AU - Evans, Philip

AU - Andersson, Monique

AU - Hayward, Gail

AU - Hood, Kerenza

AU - Nguyen-Van-Tam, Jonathan S

AU - Little, Paul

AU - Hobbs, F D Richard

AU - Khoo, Saye

AU - Butler, Christopher

AU - Lowe, David M

AU - Breuer, Judith

AU - PANORAMIC Virology Group

PY - 2024/2/23

Y1 - 2024/2/23

N2 - 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.

AB - 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.

KW - Humans

KW - Hydroxylamines

KW - Cytidine

KW - Antibodies, Viral

KW - Antiviral Agents

KW - Antibody Formation

KW - Adult

KW - Outpatients

KW - COVID-19

KW - SARS-CoV-2

U2 - 10.1038/s41467-024-45641-0

DO - 10.1038/s41467-024-45641-0

M3 - Article

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

M1 - 1652

ER -

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

Abstract

Keywords

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