ABSTRACT
ABSTRACT Background In the United States, oral nirmatrelvir-ritonavir (Paxlovid™) is authorized for use among patients aged ≥12 years with mild-to-moderate SARS-CoV-2 infection who are at risk for progression to severe COVID-19, including hospitalization. However, effectiveness under real-world conditions has not been well established. Methods We undertook a matched, observational cohort study of non-hospitalized individuals with SARS-CoV-2 infection to compare outcomes between those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Individuals were matched on testing date, age, sex, treatment/care setting, symptoms status (including presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination and SARS-CoV-2 infection, Charlson comorbidity index, and prior-year healthcare utilization. Time to hospital admission was compared between matched COVID-19 cases who received or did not receive nirmatrelvir-ritonavir. Primary analyses evaluated treatment effectiveness against any hospital admission and acute respiratory infection (ARI)-associated hospital admission, with dispense occurring 0–5 days symptom onset. Secondary analyses evaluated effectiveness against the same endpoints for all treatment dispenses. We measured treatment effectiveness as (1–adjusted hazards ratio [aHR])×100%, estimating the aHR via Cox proportional hazards models accounting for match strata and additional patient characteristics. Results Analyses included 4,329 nirmatrelvir-ritonavir recipients and 20,980 matched non-recipients who were followed ≥30 days after a positive SARS-CoV-2 outpatient test. Overall, 23,603 (93.3%) and 19,564 (78.1%) of 25,039 participants had received ≥2 and ≥3 COVID-19 vaccine doses, respectively. A total of 23,858 (94.2% of 25,039) patients were symptomatic at the point of testing, with a 2.1 day mean time from symptom onset to testing. For patients dispensed nirmatrelvir-ritonavir 0–5 days after symptom onset, effectiveness in preventing all hospital admissions was 88.1% (95% confidence interval: 49.0–97.5%) over 15 days and 71.9% (25.3–90.0%) over 30 days, respectively. Effectiveness in preventing ARI-associated hospital admissions was 88.3% (12.9–98.8%) and 87.3% (18.3–98.5%) over 15 and 30 days, respectively. In expanded analyses that included patients receiving treatment at any point during their clinical course, effectiveness was 86.6% (54.9–96.3%) and 78.0% (46.2–91.4%) in preventing all hospital admissions over 15 and 30 days, respectively, and 93.7% (52.5–99.4%) and 92.8% (53.9–99.1%) in preventing ARI-associated hospital admissions over 15 and 30 days. Subgroup analyses identified similar effectiveness estimates among patients who had received ≥2 COVID-19 vaccine doses. Implications In a real-world setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvirritonavir 0–5 days after symptom onset was associated substantial reductions in risk of hospital admission among individuals testing positive for SARS-CoV-2 infection in outpatient settings. Funding US Centers for Disease Control and Prevention, US National Institutes of Health