@article{01JHQ92FJRMCW3JV3XCEP1H887,
  abstract     = {{Background No randomised controlled trials have yet reported on the effectiveness of molnupiravir on longer term outcomes for COVID-19. The PANORAMIC trial found molnupiravir reduced time to recovery in acute COVID-19 over 28 days. We aimed to report the effect of molnupiravir treatment for COVID-19 on wellbeing, severe and persistent symptoms, new infections, health care and social service use, medication use, and time off work at 3 months and 6 months post-randomisation.

Methods This study is a follow-up to the main analysis, which was based on the first 28 days of follow-up and has been previously reported. For this multicentre, primary care, open-label, multi-arm, prospective randomised controlled trial conducted in the UK, participants were eligible if aged at least 50 years, or at least 18 years with a comorbidity, and unwell 5 days or less with confirmed COVID-19 in the community. Participants were randomly assigned to the usual care group or molnupiravir group plus usual care (800 mg twice a day for 5 days), which was stratified by age (<50 years or >= 50 years) and vaccination status (at least one dose: yes or no). The primary outcome was hospitalisation or death (or both) at 28 days; all longer term outcomes were considered to be secondary outcomes and included self-reported ratings of wellness (on a scale of 0-10), experiencing any symptom (fever, cough, shortness of breath, fatigue, muscle ache, nausea and vomiting, diarrhoea, loss of smell or taste, headache, dizziness, abdominal pain, and generally feeling unwell) rated as severe (moderately bad or major problem) or persistent, any health and social care use, health-related quality of life (measured by the EQ-5D-5L), time off work or school, new infections, and hospitalisation.

Findings Between Dec 8, 2021, and April 27, 2022, 25 783 participants were randomly assigned to the molnupiravir plus usual care group (n=12 821) or usual care group (n=12 962). Long-term follow-up data were available for 23 008 (89.2%) of 25 784 participants with 11 778 (91.9%) of 12 821 participants in the molnupiravir plus usual care group and 11 230 (86.6%) of 12 963 in the usual care group. 22 806 (99.1%) of 23 008 had at least one previous dose of a SARS-CoV-2 vaccine. Any severe (3 months: adjusted risk difference -1.6% [-2.6% to -0.6%]; probability superiority [p(sup)]>0.99; number needed to treat [NNT] 62.5; 6 months: -1.9% [-2.9% to -0.9%]; p(sup)>0.99, NNT 52.6) or persistent symptoms (3 months: adjusted risk difference -2.1% [-2.9% to -1.5%]; p(sup)>0.99; NNT 47.6; 6 months: -2.5% [-3.3% to -1.6%]; p(sup)>0.99; NNT 40) were reduced in severity, and health-related quality of life (measured by the EQ-5D-5L) improved in the molnupiravir plus usual care group at 3 months and 6 months (3 months: adjusted mean difference 1.08 [0.65 to 1.53]; p(sup)>0.99; 6 months: 1.09 [0.63 to 1.55]; p(sup)>0.99). Ratings of wellness (3 months: adjusted mean difference 0.15 (0.11 to 0.19); p(sup)>0.99; 6 months: 0.12 (0.07 to 0.16); p(sup)>0.99), experiencing any more severe symptom (3 months; adjusted risk difference -1.6% [-2.6% to -0.6%]; p(sup)=0.99; 6 months: -1.9% [-2.9% to -0.9%]; p(sup)>0.99), and health-care use (3 months: adjusted risk difference -1.4% [-2.3% to -0.4%]; p(sup)>0.99; NNT 71.4; 6 months: -0.5% [-1.5% to 0.4%]; p(sup)>0.99; NNT 200) had high probabilities of superiority with molnupiravir treatment. There were significant differences in persistence of any symptom (910 [8.9%] of 10 190 vs 1027 [11%] of 9332, NNT 67) at 6 months, and reported time off work at 3 months (2017 [17.9%] of 11 274 vs 2385 [22.4%] of 10 628) and 6 months (460 [4.4%] of 10 562 vs 527 [5.4%] of 9846; NNT 100). There were no differences in hospitalisations at long-term follow-up.

Interpretation In a vaccinated population, people treated with molnupiravir for acute COVID-19 felt better, experienced fewer and less severe COVID-19 associated symptoms, accessed health care less often, and took less time off work at 6 months. However, the absolute differences in this open-label design are small with high numbers needed to treat. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.}},
  author       = {{Harris, Victoria and Holmes, Jane and Gbinigie-Thompson, Oghenekome and Rahman, Najib M and Richards, Duncan B and Hayward, Gail and Dorward, Jienchi and Lowe, David M and Standing, Joseph F and Breuer, Judith and Khoo, Saye and Petrou, Stavros and Hood, Kerenza and Ahmed, Haroon and Carson-Stevens, Andrew and Nguyen-Van-Tam, Jonathan S and Patel, Mahendra G and Saville, Benjamin R and Francis, Nick and Thomas, Nicholas P B and Evans, Philip and Dobson, Melissa and Png, May Ee and Lown, Mark and Van Hecke, Oliver and Jani, Bhautesh D and Hart, Nigel D and Butler, Daniel and Cureton, Lucy and Patil, Meena and Andersson, Monique and Coates, Maria and Bateman, Clare and Davies, Jennifer C and Raymundo-Wood, Ivy and Ustianowski, Andrew and Yu, Ly-Mee and Hobbs, F D Richard and Little, Paul and Butler, Christopher C and Moftah, Areej and Goodman, Anna and Halifax, Rob and Turnbull, Chris and Sundaralingam, Anand and Agyeman, Akosua and Shah, Divya and Brown, Julianne and Thalasselis, Chris and Woodall, Maximillian N J and Yongblah, Francis and Howell, Aleksandra and Patel, Kavil and Hussain, Iqbal and Penfold, Ruth and Hutchinson, Simon and Poonian, Satveer and Imlach, Marie and Popoola, Olajide and Irving, Greg and Pora, Alexander and Jacobsen, Nicholas and Prasad, Vibhore and Kennard, James and Prasad, Rishabh and Khan, Umar and Razzaq, Omair and Knox, Kyle and Richardson, Scot and Krasucki, Christopher and Royal, Simon and Law, Tom and Safa, Afsana and Lee, Rem and Sehdev, Satash and Lester, Nicola and Sevenoaks, Tamsin and Lewis, David and Sheikh, Aadil and Lunn, James and Short, Vanessa and Mackintosh, Claire and Singh Sidhu, Baljinder and Mathukia, Mehul and Singh, Ivor and Moore, Patrick and Soni, Yusuf and Morton, Seb and Wilson, Pete and Murphy, Daniel and Wingfield, David and Nally, Rhiannon and Wong, Michael and Ndukauba, Chinonso and Wooding, Nick and Ogundapo, Olufunto and Woods, Sharon and Okeke, Henry and Yong, Joanna and Ahmed, Tanveer and Allcock, Damien and Atherton, George and Beltran-Martinez, Adrian and Benedict, Oluseye Emmanuel and Bird, Nigel and Brennan, Laura and Burns, Gerard and Butler, Mike and Cheng, Zelda and Danson, Ruth and De Kare-Silver, Nigel and Dhasmana, Devesh and Dickson, Jon and Engamba, Serge and Fisher, Stacey and Fox, Robin and Frost, Eve and Gaunt, Richard and Ghosh, Sarit and Gilkar, Ishtiaq and Goodman, Anna and Granier, Steve and Packham, Alice and Dowsell, Sarah and Gulati, Radhika and Patel, Amit and PANORAMIC Trial Collaborative Grp, [missing]}},
  issn         = {{1473-3099}},
  journal      = {{LANCET INFECTIOUS DISEASES}},
  keywords     = {{RESPIRATORY-TRACT INFECTION,PRESCRIBING STRATEGIES}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{68--79}},
  title        = {{Health outcomes 3 months and 6 months after molnupiravir treatment for COVID-19 for people at higher risk in the community (PANORAMIC) : a randomised controlled trial}},
  url          = {{http://doi.org/10.1016/s1473-3099(24)00431-6}},
  volume       = {{25}},
  year         = {{2025}},
}

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