Real‐world effectiveness of Azvudine versus nirmatrelvir–ritonavir in hospitalized patients with COVID‐19: A retrospective cohort study

Abstract Chinese guidelines prioritize the use of Azvudine and nirmatrelvir–ritonavir in COVID‐19 patients. Nevertheless, the real‐world effectiveness of Azvudine versus nirmatrelvir–ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir–ritonavir treatments in real‐world clinical practice, we identified 2118 hospitalized COVID‐19 patients, with a follow‐up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir–ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person‐days, p = 0.026) and all‐cause death (2.05 vs. 5.78 per 1000 person‐days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32–0.94) and all‐cause death (HR: 0.40; 95% CI: 0.16–1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID‐19 at admission, and those receiving antibiotics. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID‐19 patients compared with nirmatrelvir–ritonavir in terms of composite disease progression outcome.