Clinical effectiveness of oral antiviral agents in older patients with COVID-19 based on real-world data.

Several randomized controlled trials and real-world cohort studies have demonstrated the efficacies of nirmatrelvir plus ritonavir (NMV-r) and molnupiravir (MOV) in at-risk patients with COVID-19; however, the effectiveness of antisevere acute respiratory syndrome-coronavirus 2 treatments on older patients (≥65 years) remains unclear. This retrospective cohort study aimed to assess the clinical effectiveness of the oral antiviral agents, MOV and NMV-r, in older patients (≥65 years) infected with severe acute respiratory syndrome-coronavirus 2. Nonhospitalized older patients with COVID-19 between January 1, 2022, and December 31, 2022, were recruited from the TriNetX Research Network. Propensity score matching (PSM) was used to match patients who received either NMV-r or MOV treatment with those who did not receive any oral antiviral agents. Hazard ratios (HRs) for composite all-cause hospitalization or death during the 30-day follow-up period were calculated. PSM revealed two cohorts with 28 824 patients each having balanced baseline characteristics. The antiviral group was associated with significantly lower risk of the primary composite outcome of all-cause hospitalization or death than the control group (241 vs. 801; HR, 0.307; 95% confidence interval (CI), 0.27-0.36) during the follow-up period. For the secondary outcome, the antiviral group had a significantly lower risk of all-cause hospitalization (288 vs. 725; HR, 0.322; 95% CI, 0.28-0.37) and mortality (16 vs. 94; HR, 0.176; 95% CI, 0.10-0.30) than the control group. Moreover, the reduced risk of all-cause hospitalization or death remained consistent in patients receiving NMV-r (HR, 0.279; 95% CI, 0.24-0.33) and MOV (HR, 0.279; 95% CI, 0.21-0.38). Our results revealed that NMV-r and MOV decreased the all-cause hospitalization and death rates among older patients with COVID-19, supporting the use of antivirals in this vulnerable population.