Presentation (CTI)

OBJECTIVES: In many clinical guidelines for managing patients with COVID-19, nirmatrelvir/ritonavir is generally recommended to be prescribed within 5 days of diagnosis or symptom onset; however, the duration of acute symptoms is typically short, especially for Omicron infections, raising questions about the timing and necessity of antiviral treatment in some cases. This study examined the effect of nirmatrelvir/ritonavir at different initiation time against post-COVID conditions using real-world data.
METHODS: This retrospective cohort study utilized real-world inpatient records, vaccination, and confirmed COVID-19 case data in Hong Kong. Patients tested positive for SARS-CoV-2 between Mar 16, 2022 and Nov 9, 2023 were included. The treatment group included patients prescribed nirmatrelvir/ritonavir by different number of days after symptom onset. The primary outcomes are the post-acute inpatient death and all-cause hospitalization. Standardized-mortality-ratio weights was applied to balance covariates, and Cox proportional hazards regression was used to examine the associations.
RESULTS: Among 38,620 included patients, 22,792 received no treatment, and 9,945, 4,914, 593, 210, 82, and 84 initiated nirmatrelvir/ritonavir treatment at day 0, 1, 2, 3, 4, ≥5 after diagnosis, respectively. Compared to no treatment group, an immediate initiation of nirmatrelvir/ritonavir at day 0 was significantly associated with lower risks of post-acute mortality (hazard ratio [HR], 0.47 [95% confidence interval {CI}, 0.43 to 0.52], p value, <0·0001) and all-cause hospitalization (HR, 0.74 [95% CI, 0.71 to 0.77], p value, <0·0001). The effect size decreased significantly along with the deferred initiation of nirmatrelvir/ritonavir.
CONCLUSIONS: Our findings suggest that nirmatrelvir/ritonavir should be prescribed immediately after a COVID-19 diagnosis to maximize the benefits of antiviral treatment, not only in mitigating acute severity but also in reducing the risk of long COVID.