Greater benefits of immediate nirmatrelvir-ritonavir initiation for post-COVID outcomes: a population-based retrospective cohort study

Ka Chun Chong, Yuchen Wei, Carlos King Ho Wong, Xi Xiong, Huwen Wang, Chi Tim Hung, Conglu Li, Carrie Ho Kwan Yam, Tsz Yu Chow, Zihao Guo, Kehang Li, Aimin Yang, Chris Ka Pun Mok, David S. C. Hui, Shi Zhao (), Eng Kiong Yeoh () and Guozhang Lin ()
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Ka Chun Chong: The Chinese University of Hong Kong
Yuchen Wei: The Chinese University of Hong Kong
Carlos King Ho Wong: Hong Kong Science Park
Xi Xiong: Hong Kong Science Park
Huwen Wang: Duke-NUS Medical School
Chi Tim Hung: The Chinese University of Hong Kong
Conglu Li: The Chinese University of Hong Kong
Carrie Ho Kwan Yam: The Chinese University of Hong Kong
Tsz Yu Chow: The Chinese University of Hong Kong
Zihao Guo: The Chinese University of Hong Kong
Kehang Li: The Chinese University of Hong Kong
Aimin Yang: The Chinese University of Hong Kong
Chris Ka Pun Mok: The Chinese University of Hong Kong
David S. C. Hui: The Chinese University of Hong Kong
Shi Zhao: The Chinese University of Hong Kong
Eng Kiong Yeoh: The Chinese University of Hong Kong
Guozhang Lin: The Chinese University of Hong Kong

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: Abstract 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

Date: 2025
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DOI: 10.1038/s41467-025-64851-8

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