National Centre for Infectious Diseases, Singapore, Singapore; Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore.
Ministry of Health, Singapore, Singapore.
Clin Microbiol Infect. 2023 Oct;29(10):1328-1333. doi: 10.1016/j.cmi.2023.06.016. Epub 2023 Jun 17.
Real-world data on continued effectiveness of nirmatrelvir/ritonavir against hospitalization and severe COVID-19 in the context of widespread booster mRNA vaccine uptake and more immune-evasive Omicron sub-variants are lacking. We conducted a retrospective cohort study in adult Singaporeans aged ≥60 years presenting to primary care with SARS-CoV-2 infection, during waves of Omicron BA.2/4/5/XBB transmission.
Binary logistic regression was used to estimate the effect of treatment (receiving nirmatrelvir/ritonavir) on outcomes (hospitalization, severe COVID-19). Additional sensitivity analyses, including inverse-probability-of-treatment-weighting-adjusted analysis and adjustment using overlap weights, were performed to account for observed differences in baseline characteristics among treated/untreated cohorts.
We included 3959 nirmatrelvir/ritonavir recipients and 139 379 untreated controls. Almost 95% received ≥3 doses of mRNA vaccines; 5.4% had preceding infection. Overall 26.5% of infections occurred during the Omicron XBB period and 1.7% were hospitalized. On multivariable logistic regression, receipt of nirmatrelvir/ritonavir was independently associated with lower odds of hospitalization (adjusted odds ratio [aOR] = 0.65, 95% CI = 0.50-0.85). Consistent estimates were obtained after inverse-probability-of-treatment-weighting adjustment (aOR for hospitalization = 0.60, 95% CI = 0.48-0.75) and adjustment using overlap weights (aOR for hospitalization = 0.64, 95% CI = 0.51-0.79). Although receipt of nirmatrelvir/ritonavir was associated with lower odds of severe COVID-19, it was not statistically significant.
Outpatient usage of nirmatrelvir/ritonavir was independently associated with reduced odds of hospitalization amongst boosted older community-dwelling Singaporeans during successive waves of Omicron transmission, including Omicron XBB; however, it did not significantly reduce the already low risk of severe COVID-19 in a highly vaccinated population.
在广泛接种 mRNA 疫苗和更多免疫逃逸的奥密克戎亚变种的情况下，缺乏关于奈玛特韦/利托那韦在住院和严重 COVID-19 方面持续有效性的真实世界数据。我们在奥密克戎 BA.2/4/5/XBB 传播期间，对在初级保健机构就诊的≥60 岁成年新加坡人进行了一项回顾性队列研究。
使用二元逻辑回归来估计治疗（接受奈玛特韦/利托那韦）对结果（住院、严重 COVID-19）的影响。进行了额外的敏感性分析，包括使用逆概率治疗加权调整分析和重叠权重调整分析，以解释治疗/未治疗队列之间观察到的基线特征差异。
我们纳入了 3959 名奈玛特韦/利托那韦接受者和 139379 名未接受者。近 95%的人接种了≥3 剂 mRNA 疫苗；5.4%有既往感染史。总体而言，26.5%的感染发生在奥密克戎 XBB 期间，1.7%的人住院。多变量逻辑回归显示，接受奈玛特韦/利托那韦与较低的住院几率相关（调整后的比值比[aOR] = 0.65，95%置信区间[CI] = 0.50-0.85）。在逆概率治疗加权调整后，得到了一致的估计（住院的 aOR = 0.60，95%CI = 0.48-0.75），并且使用重叠权重进行调整后（住院的 aOR = 0.64，95%CI = 0.51-0.79）。尽管接受奈玛特韦/利托那韦与严重 COVID-19 的较低几率相关，但无统计学意义。
在奥密克戎连续传播期间，包括奥密克戎 XBB 在内，对接受过强化疫苗接种的社区居住的老年新加坡人，门诊使用奈玛特韦/利托那韦与住院几率降低独立相关；然而，在高疫苗接种人群中，它并没有显著降低严重 COVID-19 的低风险。
