目的:在这项回顾性队列研究中,我们的目的是评估临床有效性和病毒清除后使用莫诺比拉韦,在中国,以SARS-CoV-2的omicronBA.5.2和BF.7亚变体为主的COVID-19住院患者中,阿维定和帕索维。
方法:入选患者被分配到莫诺比拉韦组或阿兹夫定组或帕克斯洛维组或对照组(不服用任何抗病毒药物)。队列研究的主要结果是治疗后病毒清除和病毒负荷反弹,次要结果是28天全因死亡率。四组倾向得分匹配(1:1)。我们使用局部加权回归(LOWESS)平滑数据绘制了每种抗病毒药物干预的病毒载量趋势。使用多变量逻辑回归(逐步算法)模型来确定28天死亡率的任何危险因素。
结果:在接受任何治疗的1537名患者中,886(57.6%)接受了莫努普拉韦,390(25.4%)接受阿兹维定,94(6.1%)接受了帕克斯洛维德,和167(10.9%)没有使用任何抗病毒药物。我们的数据分析显示年龄(OR=1.05,95%CI:1.03-1.07,P<0.001),Charlson合并症指数(OR=1.32,95%CI:1.18-1.48,P<0.001),COVID-19的严重程度(P<0.001),丙种球蛋白(OR=2.04,95%CI:1.03~3.99,P=0.039)和糖皮质激素(OR=2.3,95%CI:1.19~4.69,P=0.017)是COVID-19患者28d死亡的独立预后因素。在倾向得分匹配(PSM)之后,paxlovid接受者(OR=0.22,95%CI:0.05~0.83,P=0.036)或阿兹夫定接受者(OR=0.27,95%CI:0.07~0.91,P=0.046)的28日死亡率低于配对对照组.对照组在第9-16天左右发生病毒反弹,而在三个口服抗病毒组中均未发现病毒反弹。我们发现,与paxlovid组相比,molnupiravir组在核酸转化率阴性方面的表现相当,而阿兹夫定组的表现略差于帕克斯洛维组或莫诺比拉韦组。
结论:在我们的COVID-19住院患者的回顾性队列中,莫努比拉韦,与对照相比,paxlovid和azvudine接受者显示出病毒载量更快,更稳定的减少和罕见病毒反弹对抗病毒治疗的反应。该研究支持paxlovid和azvudine的初始治疗与28天内全因死亡的风险显着降低相关。
OBJECTIVE: In this retrospective cohort study, we aimed to assess clinical effectiveness and viral clearance following the use of molnupiravir, azvudine and paxlovid in hospitalized patients with COVID-19 in China dominated by the omicron BA.5.2 and BF.7 subvariant of SARS-CoV-2.
METHODS: Enrolled patients were assigned to the molnupiravir group or the azvudine group or the paxlovid group or the control group (not taking any antiviral drugs). The primary outcome of the cohort study was viral clearance and viral burden rebound after treatment and the secondary outcome was 28-day all-cause mortality. The four groups were propensity score-matched (1:1). We plotted viral load trends for each antiviral drug intervention using locally weighted regression (LOWESS) smoothed data. Multivariate logistic regression (stepwise algorithm) models were used to determine any risk factors for 28-day mortality.
RESULTS: Of the 1537 patients receiving any treatment, 886 (57.6 %) received molnupiravir, 390 (25.4 %) received azvudine, 94 (6.1 %) received paxlovid, and 167 (10.9 %) did not use any antiviral drugs. Our data analysis showed that age (OR = 1.05, 95 % CI: 1.03-1.07, P < 0.001), Charlson comorbidty index (OR = 1.32, 95 % CI: 1.18-1.48, P < 0.001), severity of COVID-19 (P < 0.001), gamma globulin (OR = 2.04, 95 % CI: 1.03-3.99, P = 0.039) and corticosteroids use (OR = 2.3, 95 % CI: 1.19-4.69, P = 0.017) were independent prognostic factors for 28-day mortality in COVID-19 patients. After propensity score matching (PSM), the paxlovid recipients (OR = 0.22, 95 % CI: 0.05-0.83, P = 0.036) or azvudine recipients (OR = 0.27, 95 % CI: 0.07-0.91, P = 0.046) had lower 28-day mortality compared to their matched controls. Viral rebound occurred in the control group around days 9-16, while no viral rebound was found in any of the three oral antiviral groups. We found that molnupiravir group performed comparably in terms of the rate of nucleic acid conversion negative compared with the paxlovid group, while azvudine group performed slightly worse compared with the paxlovid group or molnupiravir group.
CONCLUSIONS: In our retrospective cohort of hospitalized patients with COVID-19 during the wave of omicron strain, the molnupiravir, paxlovid and azvudine recipients showed a faster and more stable decrease in viral load and rare virus rebound in response to antiviral treatments when compared to the controls. The study supported that initiation treatment with paxlovid and azvudine was associated with significantly lower risk of all-cause death within 28 days.