547. Molnupiravir and Nirmatrelvir/Ritonavir Effectiveness in Reducing the Risk for COVID-19 Disease Progression and Death

BACKGROUND: Molnupiravir (M) and Nirmatrelvir/Ritonavir (N/R) have been authorized for use in COVID-19 patients at high risk for severe disease. We aimed to evaluate the effectiveness of M and N/R in highly vulnerable SARS-CoV-2 patients using a retrospective cohort study design. METHODS: The study population consisted of SARS-CoV-2 infected non-hospitalized patients in Greece, aged 65 years or older, that received M between February 2 and March 25, 2022 and N/R between March 26 and July 20, 2022. The impact of each drug was determined via comparisons with age-matched control groups of SARS-CoV-2-positive patients who did not receive oral antiviral therapy, using as outcome (i) hospital admission with COVID-19 within 10 days after tested positive, and (ii) death from COVID-19 within 35 days from positive test. RESULTS: Overall, 4,240 M and 13,861 N/R recipients were enrolled. Administration of M significantly reduced the risk of hospitalization (Odds Ratio [OR] = 0.40, p < 0.001) and death (OR = 0.31, p < 0.001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of N/R also resulted in significant reductions in the risk of hospitalization (OR = 0.31, p < 0.001) and death (OR = 0.28, p < 0.001). Similar to M, the impact of N/R was more substantial among elderly patients and in those with high levels of drug adherence. CONCLUSION: N/R and M use prevented hospital admissions and death in a large real-world study of highly vulnerable patient populations. DISCLOSURES: All Authors: No reported disclosures