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

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.