Greater benefits of immediate nirmatrelvir-ritonavir initiation for post-COVID outcomes: a population-based retrospective cohort study
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Published on: May 9, 2025
Ka Chun Chong1, Yuchen Wei1, Carlos King Ho Wong2,3,4
1School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
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 < 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.
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