Harris Victoria, Holmes Jane, Gbinigie-Thompson Oghenekome, Rahman Najib M, Richards Duncan B, Hayward Gail, Dorward Jienchi, Lowe David M, Standing Joseph F, Breuer Judith, Khoo Saye, Petrou Stavros, Hood Kerenza, Ahmed Haroon, Carson-Stevens Andrew, Nguyen-Van-Tam Jonathan S, Patel Mahendra G, Saville Benjamin R, Francis Nick, Thomas Nicholas P B, Evans Philip, Dobson Melissa, Png May Ee, Lown Mark, van Hecke Oliver, Jani Bhautesh D, Hart Nigel D, Butler Daniel, Cureton Lucy, Patil Meena, Andersson Monique, Coates Maria, Bateman Clare, Davies Jennifer C, Raymundo-Wood Ivy, Ustianowski Andrew, Yu Ly-Mee, Hobbs F D Richard, Little Paul, Butler Christopher C
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Oxford Respiratory Trials Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK; Oxford National Institute for Health and Care Research Biomedical Research Centre, Oxford, UK.
Lancet Infect Dis. 2025 Jan;25(1):68-79. doi: 10.1016/S1473-3099(24)00431-6. Epub 2024 Sep 9.
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.
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.
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.
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.
UK Research and Innovation and National Institute for Health and Care Research.
尚无随机对照试验报告莫努匹拉韦对新冠病毒病（COVID-19）长期预后的有效性。“全景”试验发现，莫努匹拉韦可缩短急性COVID-19患者28天内的康复时间。我们旨在报告随机分组后3个月和6个月时，莫努匹拉韦治疗COVID-19对健康状况、严重和持续症状、新感染情况、医疗保健和社会服务使用情况、药物使用情况以及缺勤时间的影响。
本研究是主要分析的随访研究，主要分析基于随访的前28天，此前已报告。在英国进行的这项多中心、初级保健、开放标签、多臂、前瞻性随机对照试验中，年龄至少50岁，或至少18岁且患有合并症，且在社区确诊COVID-19后不适5天或更短时间的参与者符合入选条件。参与者被随机分配到常规治疗组或莫努匹拉韦组加常规治疗（800毫克，每日两次，共5天），并按年龄（<50岁或≥50岁）和疫苗接种状况（至少一剂：是或否）进行分层。主要结局是28天时的住院或死亡（或两者）；所有长期结局均被视为次要结局，包括自我报告的健康状况评分（0至10分）、出现任何被评为严重（中度不良或重大问题）或持续的症状（发热、咳嗽、呼吸急促、疲劳、肌肉疼痛、恶心和呕吐、腹泻、嗅觉或味觉丧失头痛、头晕、腹痛以及总体感觉不适）、任何医疗和社会护理使用情况、健康相关生活质量（通过EQ-5D-5L测量）、缺勤或缺课时间、新感染情况以及住院情况。
2021年12月8日至2022年4月27日期间，25783名参与者被随机分配到莫努匹拉韦加常规治疗组（n = 12821）或常规治疗组（n = 12962）。25784名参与者中有23008名（89.2%）获得了长期随访数据，其中莫努匹拉韦加常规治疗组12821名参与者中有11778名（91.9%），常规治疗组12963名参与者中有11230名（86.6%）。23008名参与者中有22806名（99.1%）之前至少接种过一剂SARS-CoV-2疫苗。在莫努匹拉韦加常规治疗组中，3个月时任何严重症状（调整风险差-1.6%[-2.6%至-0.6%]；概率优势[p(sup)]>0.99；需治疗人数[NNT]62.5；6个月时：-1.9%[-2.9%至-0.9%]；p(sup)>0.99，NNT 52.6）或持续症状（3个月时：调整风险差-2.1%[-2.9%至-1.5%]；p(sup)>0.99；NNT 47.6；6个月时：-2.5%[-3.3%至-1.6%]；p(sup)>0.99；NNT 40）的严重程度降低，且3个月和6个月时健康相关生活质量（通过EQ-5D-5L测量）得到改善（3个月时：调整平均差1.08[0.65至1.53]；p(sup)>0.99；6个月时：1.09[0.63至1.55]；p(sup)>0.99）。健康状况评分（3个月时：调整平均差0.15[0.11至0.19]；p(sup)>0.99；6个月时：0.12[0.07至0.16]；p(sup)>0.99）、出现任何更严重症状（3个月时；调整风险差-1.6%[-2.6%至-0.6%]；p(sup)=0.99；6个月时：-1.9%[-2.9%至-0.9%]；p(sup)>0.99）以及医疗保健使用情况（3个月时：调整风险差-1.4%[-2.3%至-0.4%]；p(sup)>0.99；NNT 71.4；6个月时：-0.5%[-1.5%至0.4%]；p(sup)>0.99；NNT 200）在莫努匹拉韦治疗组中具有较高的优势概率。6个月时任何症状的持续时间（10190名中的910名[8.9%]对9332名中的1027名[11%]，NNT 67）以及3个月（11274名中的2017名[17.9%]对10628名中的2385名[22.4%]）和6个月（10562名中的460名[4.4%]对9846名中的527名[5.4%]；NNT 100）的报告缺勤时间存在显著差异。长期随访中的住院情况无差异。
在接种疫苗的人群中，接受莫努匹拉韦治疗急性COVID-19的人感觉更好，经历的与COVID-19相关的症状更少且不那么严重，就医频率更低，6个月时缺勤时间更短。然而，在这种开放标签设计中，绝对差异较小，所需治疗人数较多。
英国研究与创新署和国家卫生与保健研究所。
