Greater benefits of immediate nirmatrelvir-ritonavir initiation for post-COVID outcomes: a population-based retrospective cohort study
Nirmatrelvir-ritonavir is generally recommended to be initiated within five days of COVID-19 symptom onset. This study examined the association between the timing of nirmatrelvir-ritonavir initiation and post-acute outcomes more precisely using territory-wide data in Hong Kong. We included patients aged ≥18 years who tested positive for SARS-CoV-2 between March 16, 2022, and November 9, 2023, and were hospitalized with COVID-19. Treatment groups were formed based on the time from the positive RT-PCR date to nirmatrelvir-ritonavir initiation. Among 15,978 patients who received nirmatrelvir-ritonavir, 10,028 (62.8%) patients were included in Day 0 group, 4973 (31.1%) in Day 1 group, and 977 (6.1%) in Day 2 or later group. The control group comprised 22,312 patients who did not receive nirmatrelvir-ritonavir. Compared with the control group, the risks of post-acute mortality were significantly lower in Day 0 group (hazard ratio [HR] 0.51, 95% CI 0.46-0.56; p < 0.0001) and Day 1 group (HR 0.66, CI 0.59-0.74; p < 0.0001), but not in Day 2 or later group. Meta-regression results showed that more immediate initiation was associated with lower risks of death and all-cause hospitalization. Our findings suggested that the antiviral should be prescribed immediately after COVID-19 diagnosis for achieving its greatest benefit on improving post-COVID outcomes.
Authors
- Xi Xiong (ORCID: https://orcid.org/0000-0002-9418-7448)
- Kehang Li (ORCID: https://orcid.org/0000-0002-3778-7068)
- Aimin Yang (ORCID: https://orcid.org/0000-0003-2968-1762)
- Zihao Guo (ORCID: https://orcid.org/0000-0001-9002-0483)
- Huwen Wang (ORCID: https://orcid.org/0000-0001-7443-9735)
- Tsz Yu Chow (ORCID: https://orcid.org/0000-0002-1295-6646)
- Carlos King Ho Wong (ORCID: https://orcid.org/0000-0002-6895-6071)
- Ka Chun Chong (ORCID: https://orcid.org/0000-0001-5610-1298)
- Eng‐Kiong Yeoh (ORCID: https://orcid.org/0000-0002-1721-9450)
- Chris Ka Pun Mok (ORCID: https://orcid.org/0000-0002-0525-6772)
- Conglu Li (ORCID: https://orcid.org/0000-0002-6210-6631)
- Shi Zhao (ORCID: https://orcid.org/0000-0001-8722-6149)
- Carrie Ho Kwan Yam (ORCID: https://orcid.org/0000-0001-8353-9711)
- Chi Tim Hung (ORCID: https://orcid.org/0000-0003-2103-8377)
- David S.C. Hui (ORCID: https://orcid.org/0000-0003-4382-2445)
- Yuchen Wei (ORCID: https://orcid.org/0000-0002-6817-9364)
- Guozhang Lin (ORCID: https://orcid.org/0009-0006-5996-2927)
Institutions
- Chinese University of Hong Kong (HK)
- London School of Hygiene & Tropical Medicine (GB)
- Duke-NUS Medical School (SG)
- University College London (GB)
- Tianjin Medical University (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-10
- DOI
- https://doi.org/10.1038/s41467-025-64851-8
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Chinese University of Hong Kong
- Natural Science Foundation of Tianjin City
- Tianjin Science and Technology Committee
- Tianjin Medical University
- Hong Kong Government
- National Science and Technology Major Project
- Health and Medical Research Fund
- Natural Science Foundation of Tianjin Municipal Science and Technology Commission