Wang Shuxia, Sun Jin, Zhang Xin, Li Man, Qin Bangguo, Liu Miao, Zhang Nan, Wang Shengshu, Zhou Tingyu, Zhang Wei, Ma Cong, Deng Xinli, Bai Yongyi, Qu Geping, Liu Lin, Shi Hui, Zhou Bo, Li Ke, Yang Bo, Li Suxia, Wang Fan, Ma Jinling, Zhang Lu, Wang Yajuan, An Li, Liu Wenhui, Chang Qing, Zhang Ru, Yin Xi, Yang Yang, Ao Qiangguo, Ma Qiang, Yan Shuangtong, Huang Haili, Song Peng, Gao Linggen, Lu Wenning, Xu Lining, Lei Li, Wang Keyu, Zhang Qi, Song Qing, Zhang Zhijian, Fang Xiangqun, He Yao, Li Tianzhi, Zhu Ping
Department of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China.
Medical School of Chinese PLA, Beijing 100853, China.
EClinicalMedicine. 2024 Feb 9;69:102468. doi: 10.1016/j.eclinm.2024.102468. eCollection 2024 Mar.
Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents.
In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population.
Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051).
Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias.
This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).
阿兹夫定和奈玛特韦/利托那韦被批准用于治疗有进展为重症感染高风险的成人轻度至中度2019冠状病毒病（COVID-19）。我们试图比较接受这两种抗病毒药物治疗的老年COVID-19重症患者的抗病毒效果和临床结局。
在这项观察性研究中，我们纳入了2022年12月至2023年1月期间入住中国人民解放军总医院第二医学中心的249例老年COVID-19重症感染患者，其中128例接受阿兹夫定治疗，66例接受奈玛特韦/利托那韦治疗，55例未接受抗病毒治疗。我们比较了三组的循环阈值（Ct）值动态变化。主要结局是疾病进展的复合结局，包括全因死亡、入住重症监护病房和开始有创机械通气。通过电子病历系统对所有纳入患者的结局进行随访。采用Kaplan-Meier法和Cox风险比例回归分析比较三组的临床结局。为了更直接地比较两种抗病毒药物的疗效，我们在两个抗病毒组之间进行倾向评分匹配，并比较匹配人群中的抗病毒疗效和临床结局。
在249例患者（平均年龄91.41岁）中，77例患者在随访期间死亡。与未接受任何抗病毒药物治疗的患者相比，奈玛特韦/利托那韦和阿兹夫定都未显示出生存获益。三组全因死亡的Cox分析显示，与未抗病毒组相比，阿兹夫定组的死亡风险为0.730（0.423 - 1.262），奈玛特韦/利托那韦组为0.802（0.435 - 1.480）。倾向评分匹配后，我们纳入了58例阿兹夫定治疗患者和58例奈玛特韦/利托那韦治疗患者。匹配后Ct值的拟合曲线表明，奈玛特韦/利托那韦治疗早期病毒下降速率似乎超过阿兹夫定，但无统计学意义。阿兹夫定似乎与较低的复合结局风险（HR：1.676，95%CI：0.805 - 3.488）和短期全因死亡风险（HR：1.291，95%CI：0.546 - 3.051）相关。
与奈玛特韦/利托那韦相比，接受阿兹夫定治疗患者的抗病毒效果和生存曲线趋势相似。在这个有限的队列中，抗病毒治疗未显示出显著的临床获益。这种缺乏临床获益可能归因于潜在偏倚。
本研究得到“国家重点研发计划”（资助编号2020YFC2008900）和国防科技创新特区项目（223 - CXCY - N101 - 07 - 18 - 01）的支持。
