Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, Saint Louis, Missouri, USA.
Veterans Research and Education Foundation of Saint Louis, Saint Louis, Missouri, USA.
BMJ. 2023 Apr 25;381:e074572. doi: 10.1136/bmj-2022-074572.
To examine whether treatment with the antiviral agent molnupiravir during the first five days of SARS-CoV-2 infection is associated with reduced risk of post-acute adverse health outcomes.
Cohort study.
US Department of Veterans Affairs.
229 286 participants who tested positive for SARS-CoV-2 between 5 January 2022 and 15 January 2023, had at least one risk factor for progression to severe covid-19, and survived the first 30 days after testing positive were enrolled. 11 472 participants received a prescription for molnupiravir within five days of the positive test result and 217 814 received no covid-19 antiviral or antibody treatment (no treatment group).
Risks of post-acute sequelae of SARS-CoV-2 (PASC, defined based on a prespecified set of 13 post-acute sequelae), post-acute death, post-acute hospital admission, and each individual post-acute sequela between the molnupiravir group and no treatment group were examined after application of inverse probability weighting to balance the treatment and no treatment groups. Post-acute outcomes were ascertained from 30 days after the first SARS-CoV-2 positive test result until end of follow-up. Risks on the relative scale (relative risk or hazard ratio) and absolute scale (absolute risk reduction at 180 days) were estimated.
Compared with no treatment, molnupiravir use within five days of a positive SARS-CoV-2 test result was associated with reduced risk of PASC (relative risk 0.86 (95% confidence interval 0.83 to 0.89); absolute risk reduction at 180 days 2.97% (95% confidence interval 2.31% to 3.60%)), post-acute death (hazard ratio 0.62 (0.52 to 0.74); 0.87% (0.62% to 1.13%)), and post-acute hospital admission (0.86 (0.80 to 0.93); 1.32% (0.72% to 1.92%)). Molnupiravir was associated with reduced risk of eight of the 13 post-acute sequelae: dysrhythmia, pulmonary embolism, deep vein thrombosis, fatigue and malaise, liver disease, acute kidney injury, muscle pain, and neurocognitive impairment. Molnupiravir was also associated with reduced risk of PASC in people who had not received a covid-19 vaccine, had received at one or two vaccine doses, and had received a booster dose, and in people with primary SARS-CoV-2 infection and reinfection.
In people with SARS-CoV-2 infection and at least one risk factor for progression to severe covid-19, compared with no treatment, molnupiravir use within five days of infection was associated with reduced risk of PASC in people who had not received a covid-19 vaccine, had received one or two vaccine doses, and had received a booster dose, and in those with primary SARS-CoV-2 infection and reinfection. Among people at high risk of progression to severe covid-19, molnupiravir use within five days of SARS-CoV-2 infection may be a viable approach to reduce the risk of PASC.
研究在 SARS-CoV-2 感染的前 5 天内使用抗病毒药物莫那比拉韦是否与降低急性后不良健康结局的风险有关。
队列研究。
美国退伍军人事务部。
2022 年 1 月 5 日至 2023 年 1 月 15 日期间检测出 SARS-CoV-2 阳性的 229286 名参与者，至少有一个进展为严重 covid-19 的风险因素，并且在检测阳性后的第 30 天存活下来。11472 名参与者在阳性检测结果后 5 天内接受了莫那比拉韦的处方，217814 名参与者未接受 covid-19 抗病毒或抗体治疗（无治疗组）。
SARS-CoV-2（定义为根据预先确定的 13 种急性后后遗症集确定）、急性后死亡、急性后住院和莫那比拉韦组和无治疗组之间每个个体急性后后遗症的急性后后遗症风险。急性后结果从第一次 SARS-CoV-2 阳性检测结果后 30 天开始，直到随访结束。在应用逆概率加权以平衡治疗组和无治疗组后，确定了急性后结果。与无治疗相比，在 SARS-CoV-2 检测呈阳性后的 5 天内使用莫那比拉韦与急性后后遗症风险降低相关（相对风险 0.86（95%置信区间 0.83 至 0.89）；180 天绝对风险降低 2.97%（95%置信区间 2.31%至 3.60%）），急性后死亡（风险比 0.62（0.52 至 0.74）；0.87%（0.62%至 1.13%））和急性后住院（0.86（0.80 至 0.93）；1.32%（0.72%至 1.92%））。莫那比拉韦与 13 种急性后后遗症中的 8 种风险降低相关：心律失常、肺栓塞、深静脉血栓形成、疲劳和不适、肝病、急性肾损伤、肌肉疼痛和神经认知障碍。莫那比拉韦还与未接种 covid-19 疫苗、接种一剂或两剂疫苗和接种加强剂的人以及原发性 SARS-CoV-2 感染和再感染的人的急性后后遗症风险降低相关。
在 SARS-CoV-2 感染且至少有一个进展为严重 covid-19 的风险因素的人群中，与无治疗相比，在感染后 5 天内使用莫那比拉韦与未接种 covid-19 疫苗、接种一剂或两剂疫苗以及接种加强剂的人的急性后后遗症风险降低相关，以及原发性 SARS-CoV-2 感染和再感染的人。在有进展为严重 covid-19 高风险的人群中，在 SARS-CoV-2 感染后 5 天内使用莫那比拉韦可能是降低急性后后遗症风险的一种可行方法。
