Association of Azvudine with severe outcomes among hospitalized patients with COVID-19 during an omicron-dominance period in Wuhan, China: a single-center, retrospective, matched cohort study.

backgroundConstantly emerging SARS-CoV-2 genetic variants with potent immune escape kept the COVID-19 pandemic ongoing. Apart from vaccination, effective antiviral drug is necessary to achieve clinical improvement, especially for hospitalized patients. To date, there was limited data on the clinical effectiveness of Azvudine. This study aimed to provide a comprehensive assessment of the effectiveness of Azvudine among hospitalized COVID-19 patients in a real-world healthcare setting.

methodIn this single-center, retrospective cohort study, hospitalized patients with laboratory-confirmed SARS-CoV-2 infection from Dec 1, 2022 to May 31, 2023 were recruited in a tertiary hospital in Wuhan, China. Azvudine recipients and controls were propensity-score matched with a ratio of 1:1, based on age, sex, baseline Charlson comorbidity index, time from symptom onset to treatment exposure, initiation of concomitant treatment at admission, and abnormality of chest computed tomography image. The primary outcomes included a composite measure of severe outcomes (ICU admission and invasive mechanical ventilation), and all-cause death, and the secondary outcome was the time to negative nucleic acid conversion. Subgroup analyses were performed according to the matching covariates. The incidence rate was computed, and the hazard ratio (HR) was estimated by using the Cox proportional hazards regression model for each outcome.

resultsA total of 4 979 hospitalized patients (mean age [SD]: 65.4 [20.1] years) with confirmed COVID-19 diagnosis were identified during the study period. After screening and matching, 703 Azvudine recipients, and 703 matched controls were eligible for the primary outcomes, and 201 Azvudine recipients and 201 matched controls were included for the secondary outcome. The median follow-up period was 12 days. The Azvudine users were associated with a significantly lower risk of all-cause death (crude incidence rate: 17.3 per 10 000 person-days [95%CI: 10.6, 28.3] vs. 41.3 per 10 000 person-days [95%CI: 28.4, 52.7]; HR: 0.44 [95%CI: 0.25, 0.78]) and composite sever outcome measure (crude incidence rate: 74.0 per 10 000 person-days [95%CI: 58.0, 94.5] vs. 191.6 per 10 000 person-days [95%CI: 164.6, 222.9]; HR: 0.38 [95%CI: 0.28, 0.51]) than matched controls. Significant protective effectiveness was also observed in ICU admission, and invasive mechanical ventilation. Prescribing Azvudine was also associated with a significantly higher rate of negative nucleic acid conversion (crude incidence rate: 1512.4 per 10 000 person-days [95%CI: 1331.6, 1717.8] vs. 983.8 per 10 000 person-days [95%CI: 862.8, 1121.9]; HR: 1.52 [95%CI: 1.25, 1.86]) than the matched controls. Similar patterns were observed in subgroup analyses.

conclusionDuring a SARS-CoV-2 Omicron variants predominant period, initiation of Azvudine could provide considerable protection against all-cause death, composite severe outcome measure, and result in a significantly shorter nucleic acid conversion time among hospitalized patients with COVID-19. A wider use of Azvudine in clinical settings should be considered.