Association of Nirmatrelvir-ritonavir with intubation or mortality risks in severe COVID-19 patients: a comparative study

OBJECTIVE: This study aimed to evaluate the association between the use of Nirmatrelvir-ritonavir (NMVr) and the risk of intubation or in-hospital mortality among severe COVID-19 patients using real-world data. METHODS: A retrospective cohort from the First Affiliated Hospital of Xiamen University, ranging from December 15, 2022 to February 15, 2023, was utilized. To control for confounding factors, multivariable Cox proportional-hazards regression models were applied, adjusted using the inverse probability of treatment weighting (IPTW) based on propensity scores. RESULTS: A total of 1436 consecutive patients with COVID-19 were included. 265 patients were included in the final analysis, of whom 169 received the treatment of NMVr and 96 did not. The application of NMVr was significantly associated with a reduced risk of the composite endpoint after adjustment (HR, 0.58; 95% CI, 0.35 to 0.97; P = 0.0374). The results were robust to various sensitivity analyses. CONCLUSIONS: The study suggests that NMVr administration is associated with a lower risk of adverse outcomes in severe COVID-19 patients, underscoring the necessity for additional trials to confirm its therapeutic efficacy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12123-7.