ABSTRACT
BackgroundIn 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. MethodsWe 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])x100%, estimating the aHR via Cox proportional hazards models accounting for match strata and additional patient characteristics. ResultsAnalyses 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. ImplicationsIn 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. FundingUS Centers for Disease Control and Prevention, US National Institutes of Health
ABSTRACT
Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases had 15% (95% confidence interval: 9-21%) and 38% (27-49%) higher adjusted odds of having received 3 and [≥]4 COVID-19 vaccine doses, respectively, than time-matched BA.2 cases, as well as 55% (43-69%) higher adjusted odds of prior documented infection. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals.
