Azvudine and nirmatrelvir–ritonavir in hospitalized patients with moderate‐to‐severe COVID‐19: Emulation of a randomized target trial

Abstract

AbstractTo examine the effectiveness of azvudine and nirmatrelvir–ritonavir in treating hospitalized patients with moderate‐to‐severe COVID‐19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate‐to‐severe COVID‐19 without contraindications for azvudine or nirmatrelvir–ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir–ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all‐cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent‐to‐treat analyses, azvudine reduced all‐cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12–0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24–0.92). Nirmatrelvir–ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17–1.05), and its composite with all‐cause death (HR: 0.38; 95% CI: 0.18–0.81). The study did not identify credible subgroup effects. The per–protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir–ritonavir improved the prognosis of hospitalized adults with moderate‐to‐severe COVID‐19