Abstract
PURPOSE: We describe nirmatrelvir/ritonavir (NMV/r) effectiveness in preventing hospitalization among COVID-19 patients at high risk of severe disease. METHODS: An ongoing US population-based observational cohort study with retrospective and prospective collection of national electronic healthcare data collected from the US Optum® deidentified COVID-19 Electronic Health Record dataset during December 22, 2021-July 20, 2022. Participants were ≥12 years old; had a positive SARS-CoV-2 test, COVID-19 diagnosis, or NMV/r prescription; and were at high risk of severe COVID-19 based on demographic/clinical characteristics. Potential confounders between groups were balanced using propensity score matching. Immortal time bias was addressed. Hospitalization rates within 30 days from COVID-19 diagnosis were evaluated. Sensitivity analyses included 15-day hospitalization, chart review to investigate incidental hospitalization effects, and exclusion of patients identified as having COVID-19 based on NMV/r prescription alone. Outcomes were also evaluated by race, age, and COVID-19 vaccine status. FINDINGS: Overall, 12,440 and 234,123 patients were included in the NMV/r and non-NMV/r groups, respectively. After propensity score matching, baseline characteristics were well balanced across groups (NMV/r, n = 12,439; non-NMV/r, n = 36,490). Incidence of hospitalization (95% CI) within 30 days was 0.90% (0.74%-1.08%) for the NMV/r group and 5.91% (5.67%-6.16%) for the non-NMV/r group, with relative risk (95% CI) of 0.15 (0.13-0.18; 85% risk reduction). NMV/r was comparably effective in Black patients (relative risk, 0.19 [0.10-0.34]; 81% risk reduction). Sensitivity analyses supported the main outcomes. IMPLICATIONS: Real-world NMV/r effectiveness against hospitalization during Omicron predominance among COVID-19 patients at high risk of severe disease supports demonstrated clinical trial efficacy. Black patients underutilized NMV/r despite high effectiveness.