Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, and Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (E.Y.F.W., C.K.H.W.).
Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (V.K.C.Y., F.W.T.C.).
Ann Intern Med. 2023 Apr;176(4):505-514. doi: 10.7326/M22-3057. Epub 2023 Mar 14.
Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain.
To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak.
Target trial emulation study.
Electronic health databases in Hong Kong.
The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 ( = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 ( = 7119).
Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir.
Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days.
The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people.
The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist.
Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed.
Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.
住院患者是否从 COVID-19 口服抗病毒药物中获益尚不确定。
在奥密克戎疫情期间，检测莫那比拉韦和奈玛特韦/利托那韦在住院 COVID-19 患者中的真实世界疗效。
目标试验模拟研究。
中国香港的电子健康数据库。
莫那比拉韦模拟试验纳入 2022 年 2 月 26 日至 7 月 18 日期间年龄在 18 岁或以上的 COVID-19 住院患者（=16495 人）。奈玛特韦/利托那韦模拟试验纳入 2022 年 3 月 16 日至 7 月 18 日期间年龄在 18 岁或以上的 COVID-19 住院患者（=7119 人）。
COVID-19 住院后 5 天内开始使用莫那比拉韦或奈玛特韦/利托那韦与未开始使用莫那比拉韦或奈玛特韦/利托那韦。
28 天内全因死亡率、入住重症监护病房（ICU）或使用呼吸机支持的疗效。
在 COVID-19 住院患者中使用口服抗病毒药物与全因死亡率降低相关（莫那比拉韦：风险比[HR]，0.87[95%CI，0.81 至 0.93]；奈玛特韦/利托那韦：HR，0.77[CI，0.66 至 0.90]），但与 ICU 入院（莫那比拉韦：HR，1.02[CI，0.76 至 1.36]；奈玛特韦/利托那韦：HR，1.08[CI，0.58 至 2.02]）或呼吸机支持需求（莫那比拉韦：HR，1.07[CI，0.89 至 1.30]；奈玛特韦/利托那韦：HR，1.03[CI，0.70 至 1.52]）无显著风险降低。药物治疗与 COVID-19 疫苗接种剂次之间无显著交互作用，支持无论接种状态如何，口服抗病毒药物均有效。奈玛特韦/利托那韦治疗与年龄、性别或 Charlson 合并症指数之间无显著交互作用，而莫那比拉韦在老年人中效果更好。
入住 ICU 或需要呼吸机支持的结局可能无法捕获所有严重 COVID-19 病例；可能存在肥胖和健康行为等未测量的混杂因素。
莫那比拉韦和奈玛特韦/利托那韦降低了疫苗接种和未接种住院患者的全因死亡率。未观察到 ICU 入院或呼吸机支持需求的显著降低。
中国香港特别行政区政府卫生署卫生及医疗研究基金对 COVID-19 的研究；研究资助局协作研究基金；中国香港特别行政区政府卫生署。
