Objective To emulate a randomized target trial to estimate the association between the antiviral drug molnupiravir and hospital admission or death in adults with SARS-CoV-2 infection in the community during the omicron predominant era who were at high risk of progression to severe covid-19. Design Emulation of a randomized target trial using electronic health records. Setting US Department of Veterans Affairs. Participants 85 998 adults with SARS-CoV-2 infection between 5 January and 30 September 2022 and at least one risk factor for progression to severe covid-19: 7818 participants were eligible for and treated with molnupiravir and 78 180 received no treatment. Main outcomes measure The primary outcome was a composite of hospital admission or death at 30 days. The clone method with inverse probability of censoring weighting was used to adjust for informative censoring and balance baseline characteristics between the groups. The cumulative incidence function was used to estimate the relative risk and the absolute risk reduction at 30 days. Results Molnupiravir was associated with a reduction in hospital admissions or death at 30 days (relative risk 0.72 (95% confidence interval 0.64 to 0.79)) compared with no treatment; the event rates for hospital admission or death at 30 days were 2.7% (95% confidence interval 2.5% to 3.0%) for molnupiravir and 3.8% (3.7% to 3.9%) for no treatment; the absolute risk reduction was 1.1% (95% confidence interval 0.8% to 1.4%). Molnupiravir appeared to be effective in those who had not been vaccinated against covid-19 (relative risk 0.83 (0.70 to 0.97) and absolute risk reduction 0.9% (0.2% to 1.9%)), had received one or two vaccine doses (0.69 (0.56 to 0.83) and 1.3% (0.7% to 1.9%)), and had received a booster dose (0.71 (0.58 to 0.83) and 1.0% (0.5% to 1.4%)); in those infected during the era when the omicron subvariant BA.1 or BA.2 was predominant (0.72 (0.62 to 0.83) and 1.2% (0.7% to 1.6%)) and when BA.5 was predominant (0.75 (0.66 to 0.86) and 0.9% (0.5% to 1.3%)); and in those with no history of SARS-CoV-2 infection (0.72 (0.64 to 0.81) and 1.1% (0.8% to 1.4%)) and with a history of SARS-CoV-2 infection (0.75 (0.58 to 0.97) and 1.1% (0.1% to 1.8%)). Conclusions The findings of this emulation of a randomized target trial suggest that molnupiravir might have reduced hospital admission or death at 30 days in adults with SARS-CoV-2 infection in the community during the recent omicron predominant era who were at high risk of progression to severe covid-19 and eligible for treatment with molnupiravir. The data that support the findings of this study are available from the US Department of Veterans Affairs. Veterans Affairs data are made freely available to researchers behind a firewall with an approved Veterans Affairs study protocol. For more information, please visit or contact VIReC@va.gov.

中文翻译：

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Molnupiravir 与 covid-19 成人患者入院或死亡的风险：使用电子健康记录模拟随机目标试验

目的 模拟一项随机目标试验，评估抗病毒药物 molnupiravir 与 omicron 主导时代社区中 SARS-CoV-2 感染成人入院或死亡之间的关系，这些成人有进展为重症 covid-19 的高风险。使用电子健康记录设计随机目标试验的模拟。设置美国退伍军人事务部。参与者 2022 年 1 月 5 日至 9 月 30 日期间感染 SARS-CoV-2 的 85 998 名成年人，且至少有一个进展为严重 covid-19 的危险因素：7 818 名参与者符合接受莫努匹韦治疗的条件，78 180 名参与者未接受治疗。主要结局指标 主要结局是 30 天入院或死亡的综合结果。使用具有审查权重逆概率的克隆方法来调整信息审查并平衡各组之间的基线特征。累积发生率函数用于估计 30 天时的相对风险和绝对风险降低。结果 与不治疗相比，莫努匹拉韦可减少 30 天住院或死亡人数（相对风险 0.72（95% 置信区间 0.64 至 0.79））；莫努匹拉韦组 30 天入院或死亡事件发生率为 2.7%（95% 置信区间 2.5% 至 3.0%），不治疗组为 3.8%（3.7% 至 3.9%）；绝对风险降低了 1.1%（95% 置信区间为 0.8% 至 1.4%）。Molnupiravir 似乎对那些未接种 covid-19 疫苗的人有效（相对风险为 0.83（0.70 至 0.97），绝对风险降低 0.9%（0.2% 至 1.9%）），已接受一剂或两剂疫苗（0.69（0.69%） 0.56至0.83）和1.3%（0.7%至1.9%）），并已接受加强剂量（0.71（0.58至0.83）和1.0%（0.5%至1.4%））；在 omicron 亚变体 BA.1 或 BA.2 占主导地位（0.72（0.62 至 0.83）和 1.2%（0.7% 至 1.6%））和 BA.5 占主导地位（0.75（0.66 至 0.86）的时代感染的人中）和0.9%（0.5%至1.3%））；无 SARS-CoV-2 感染史的人群（0.72（0.64 至 0.81）和 1.1%（0.8% 至 1.4%））和有 SARS-CoV-2 感染史的人群（0.75（0.58 至 0.97）和1.1%（0.1%至1.8%））。结论 这项随机目标试验的模拟结果表明，molnupiravir 可能会减少最近 omicron 占主导地位的社区中 SARS-CoV-2 感染成人的入院率或 30 天时的死亡率，这些成人处于进展为高风险的状态。患有严重的 covid-19 且有资格接受 molnupiravir 治疗。支持这项研究结果的数据可从美国退伍军人事务部获得。退伍军人事务部数据可通过经批准的退伍军人事务部研究协议免费提供给防火墙后面的研究人员。欲了解更多信息，请访问或联系 VIReC@va.gov。