Effectiveness of nirmatrelvir-ritonavir against hospital admission: a matched cohort study in a large US healthcare system

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

Is COVID-19 seasonal? A time series modeling approach

BackgroundDetermining whether SARS-CoV-2 is or will be seasonal like other respiratory viruses is critical for public health planning, including informing vaccine policy regarding the optimal timing for deploying booster doses. To help answer this urgent public health question, we evaluated whether COVID-19 case rates in the United States and Europe followed a seasonal pattern using time series models. MethodsWe analyzed COVID-19 data from Our World in Data from Mar 2020 through Apr 2022 for the United States (and Census Region) and five European countries (Italy, France, Germany, Spain, and the United Kingdom). For each, anomalies were identified using Twitters decomposition method and Generalized Extreme Studentized Deviate tests. We performed sensitivity analyses to determine the impact of data source (i.e., using US Centers for Disease Control and Prevention [CDC] data instead of OWID) and whether findings were similar after adjusting for multiple covariates. Finally, we determined whether our time series models accurately predicted seasonal influenza trends using US CDC FluView data. ResultsAnomaly plots detected COVID-19 rates that were higher than expected between November and March each year in the United States and Europe. In the US Southern Census Region, in addition to seasonal peaks in the fall/winter, a second peak in Aug/Sep 2021 was identified as anomalous. Results were robust to sensitivity analyses. ConclusionsOur results support employing annual protective measures against SARS-CoV-2 such as administration of seasonal booster vaccines or other non-pharmaceutical interventions in a similar timeframe as those already in place for influenza prevention. Summary of the Main PointAlthough SARS-CoV-2 continues to cause morbidity and mortality year-round due to its high transmissibility and rapid viral evolution, our results suggest that COVID-19 activity in the United States and Europe peaks during the traditional winter viral respiratory season.

Evaluation of COVID-19 vaccine breakthrough infections among immunocompromised patients fully vaccinated with BNT162b2

ObjectiveTo evaluate COVID-19 vaccine breakthrough infections among immunocompromised (IC) individuals. MethodsIndividuals vaccinated with BNT162b2 were selected from the US HealthVerity database (12/10/2020-7/8/2021). COVID-19 vaccine breakthrough infections were examined in fully vaccinated ([≥]14 days after 2nd dose) IC individuals (IC cohort), 12 mutually exclusive IC condition groups, and a non-IC cohort. IC conditions were identified using an algorithm based on diagnosis codes and immunosuppressive (IS) medication usage. ResultsOf 1,277,747 individuals [≥]16 years of age who received 2 BNT162b2 doses, 225,796 (17.7%) were identified as IC (median age: 58 years; 56.3% female). The most prevalent IC conditions were solid malignancy (32.0%), kidney disease (19.5%), and rheumatologic/inflammatory conditions (16.7%). Among the fully vaccinated IC and non-IC cohorts, a total of 978 breakthrough infections were observed during the study period; 124 (12.7%) resulted in hospitalization and 2 (0.2%) were inpatient deaths. IC individuals accounted for 38.2% (N=374) of all breakthrough infections, 59.7% (N=74) of all hospitalizations, and 100% (N=2) of inpatient deaths. The proportion with breakthrough infections was 3 times higher in the IC cohort compared to the non-IC cohort (N=374 [0.18%] vs. N=604 [0.06%]; unadjusted incidence rates were 0.89 and 0.34 per 100 person-years, respectively. Organ transplant recipients had the highest incidence rate; those with >1 IC condition, antimetabolite usage, primary immunodeficiencies, and hematologic malignancies also had higher incidence rates compared to the overall IC cohort. Incidence rates in older ([≥]65 years old) IC individuals were generally higher versus younger IC individuals (<65). LimitationsThis retrospective analysis relied on coding accuracy and had limited capture of COVID-19 vaccine receipt. ConclusionsCOVID-19 vaccine breakthrough infections are rare but are more common and severe in IC individuals. The findings from this large study support FDA authorization and CDC recommendations to offer a 3rd vaccine dose to increase protection among IC individuals.