KP.2-Adapted BNT162b2 COVID-19 Vaccine Uptake and Effectiveness in Children.

2024-2025 BNT162b2 KP.2 COVID-19 full season vaccine effectiveness from vaccine registries linked to administrative claims in two states: A cohort study in non-immunocompromised adults.

BACKGROUND Data on effectiveness of COVID-19 vaccinations during the 2024-2025 respiratory season are limited, particularly among those with underlying medical conditions (UMC). We estimated BNT162b2 KP.2 vaccine effectiveness (VE) against COVID-19-associated hospital admission, emergency department (ED), and urgent care (UC) visits in two U.S. states. METHODS Retrospective cohort study of non-immunocompromised adults living in Louisiana or California, with ≥1 year prior continuous enrollment in insurance plans contributing to the HealthVerity claims database beginning August 22, 2024. The effectiveness of BNT162b2 KP.2 vaccine (2024-2025 formulation, hereafter referred to as BNT162b2), measured as a time-varying exposure against hospital admission, ED, or UC encounters with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code U07.1 was calculated as 1 - adjusted hazard ratio using Cox proportional hazard models adjusted for age group, sex, state, insurance payor, presence or absence of UMCs, and pre-index healthcare utilization. Stratifications included those aged 65 years and older, those aged 18-64 years with UMCs, and those aged 18-64 years without UMCs. RESULTS The cohort included 6,256,421 individuals (93% California, 7% Louisiana); 330,565 (5%) received the BNT162b2 vaccine. Vaccinated individuals were older and had more comorbidities, wellness visits, and prior influenza vaccination. Overall, 66% of the study population had ≥1 UMC; the most prevalent conditions were obesity (25%), history of immunocompromised conditions (23%), and mental health conditions (19%). COVID-19-related encounter rates for ED, UC or hospitalization were lower among vaccinated compared to unvaccinated persons (25.1 vs 36.3 per 100,000 person-months). Among all adults, VE was 37% against hospitalization, 12% against ED/UC encounters, and 16% against ED/UC/hospitalization encounters. Results were similar across age groups and UMCs. CONCLUSIONS BNT162b2 provided protection against COVID-19-associated outcomes of ED, UC or hospitalization among non-immunocompromised U.S. adults, including those with UMCs, over the course of the 2024-2025 respiratory virus season, supporting continued vaccine recommendations. REGISTRATION This study was posted on clinicaltrials.gov prior to analyses (NCT06923137).

Effectiveness of BNT162B2 and CoronaVac vaccines in reducing COVID-19 severity among children aged 3-4 years in Brazil.

INTRODUCTION National population-based databases from large countries can provide real-world estimates of COVID-19 vaccine effectiveness. This analysis examined the effectiveness of BNT162b2 and CoronaVac against severe COVID-19-related outcomes in children aged 3 to 4 years during the Omicron phase of the pandemic in Brazil. METHODS This nationwide population-based cohort study assessed incidence rate ratios for hospitalization due to COVID-19-associated severe acute respiratory syndrome, invasive ventilatory support, and death among children aged 3 to 4 years, according to vaccination status (unvaccinated, 1 dose, or 2 doses), during 2022-2023. The study period spanned epidemiological weeks 31-52 of 2022 and weeks 1-13 of 2023. Data on laboratory-confirmed COVID-19-related hospitalizations, clinical outcomes, and vaccination status were obtained from OpenDATASUS, and vaccination coverage was estimated using data from the Brazilian Ministry of Health COVID-19 vaccination dashboard. RESULTS Among children aged 3 to 4 years completion of the primary series increased to 15% for CoronaVac and 2% for BNT162b2 during the study period, corresponding to 797,956 and 79,650 individuals receiving the second dose, respectively. A total of 963 children were hospitalized with COVID-19-associated severe acute respiratory syndrome. Vaccine effectiveness against hospitalization was 79.0% (95% CI, 69.9%-85.4%) after partial vaccination and 49.2% (95% CI, 32.5%-61.9%) after completion of the primary series (p < 0.01). Effectiveness against invasive mechanical ventilation was 77.6% and 79.1%, respectively; no deaths occurred among fully vaccinated children. Direct comparisons between vaccines were not feasible because of the lower proportion of BNT162b2 recipients. CONCLUSIONS COVID-19 vaccination, predominantly based on the CoronaVac vaccine, was associated with a significant reduction in severe outcomes among children aged 3-4 years, providing robust evidence to support pediatric immunization strategies and public health efforts.

Adapted XBB.1.5 vaccine effectiveness against severe COVID-19 outcomes among immunocompromised persons in 2023-24 in six European countries: a VEBIS-EHR network study.

BACKGROUND We estimated the XBB.1.5 vaccine effectiveness (VE) against COVID-19 hospitalization and death in Belgium, Denmark, Italy, Portugal, Spain (Navarre), and Sweden following the 2023-24 fall vaccination campaign among immunocompromised persons (ICPs). RESEARCH DESIGN AND METHODS We conducted a multi-country retrospective cohort study using electronic health records. Study sites identified ICPs aged ≥18 years through a common set of immunocompromising conditions and follow-up started the first day of the 2023 vaccination campaign until 12 months later. VE was calculated by time since vaccination (14-59, 60-119, 120-179, 180-365 days after vaccination) for ICPs by pooling study site level confounder adjusted hazard ratios (aHR) of vaccination, estimated with Cox proportional hazards regression models, using a random effect meta-analysis with VE = 100 × (1-pooled aHR). RESULTS The XBB.1.5 VE was 52% (95% confidence interval (CI): 41 to 60) and 75% (95%CI: 60 to 84) against hospitalization and death, respectively, 14-59 days after vaccination, and VE decreased with time since vaccination with no remaining protection at 180-365 days after vaccination. CONCLUSION Adapted XBB.1.5 vaccine provided moderate protection within 120 days after vaccination against severe COVID-19 outcomes among ICPs aged ≥18 years during a period with BA.2.86/JN.1 replacing the XBB.1.5 variant.

Effectiveness and waning of the fourth dose mRNA COVID-19 vaccines for the prevention of SARS-CoV2 infection related hospitalisations and deaths.

BACKGROUND Real-world data studies suggest that the vaccine effectiveness (VE) of a fourth mRNA vaccine dose against SARS-CoV2 infection related hospitalisation wanes after a few months, potentially warranting consideration of additional booster doses. METHODS A multi-database cohort study was conducted through the Data Analysis and Real World Interrogation Network (DARWIN EU®) using routinely collected electronic health records from the UK (CPRD GOLD), the Netherlands (IPCI), and Spain (SIDIAP) from January 2021 to June 2023. The study included individuals aged 12 and above, vaccinated with at least three doses. We matched fourth-dose to third-dose vaccinated individuals using a weekly sequential approach, defining the date of the last dose received by the exposed individual as index date. Primary outcomes were SARS-CoV2 infection related death and hospitalisation. Hazard ratios (HR) were estimated using Cox proportional hazard models, with VE defined as the percentage of 1 minus HR. Waning of VE was assessed at monthly intervals. FINDINGS A total number of 975,496 matched pairs were identified from the three databases, with a median age of 63-78. The pooled VE of a fourth vaccine dose against SARS-CoV2 infection related death compared to three vaccine doses was 30% (95%CI 9 to 46, I2=0). VE against SARS-CoV2 infection related hospitalisation was 26% (19% to 33%) and 46% (15% to 66%), in Spain (SIDIAP, median follow-up 8 weeks) and Netherlands (IPCI, median follow-up 21 weeks) respectively. VE of a fourth dose started waning at 4-8 weeks after vaccination. INTERPRETATION A fourth dose of a mRNA COVID-19 vaccination was effective against SARS-CoV2 infection related death and hospitalisation. However, effectiveness waned over time. Periodic revaccination should be considered, with recommendations regarding booster timing taking into account circulating variants, patterns of viral transmission, and population uptake. FUNDING European Medicines Agency.

COVID-19 outcomes among vaccinated and unvaccinated patients receiving disease-modifying antirheumatic drugs and biologic therapies: a retrospective multihospital cohort study.

Real-world effectiveness of early nirmatrelvir/ritonavir initiation after COVID-19 diagnosis in outpatient setting against severe illness, hospitalization, death, and long COVID in N3C

COVID-19 has placed a monumental burden on the health care system globally. Although no longer a public health emergency, there is still a pressing need for effective treatments that prevent adverse outcomes associated with this disease. Nirmatrelvir/ritonavir (NMV-R) is a promising and potentially effective antiviral, which until recently was under emergency use authorization. Our objective was to evaluate the real-world effectiveness of NMV-R in preventing severe illness, hospitalization, death and long-COVID in a large nationwide cohort of outpatients with COVID-19. Population-based retrospective cohort study of patients with a SARS-CoV-2 positive test or diagnosis (index) date between December 2021 and February 2023 within the National COVID Cohort Collaborative (N3C), with at least one risk factor for severe COVID-19, no evidence of contraindicated medical conditions or medication use, and no hospital or emergency department visit or death within 24 hours of eligibility. We emulated a sequence of target trials beginning on each of the first five days of diagnosis with COVID-19. We identified 921,034 eligible person-trials (each representing a patient’s eligibility at a given diagnosis day across sequential emulated trials), of which 77,449 were initiators and 846,585 were non-initiators of NMV-R treatment. NMV-R Initiators were matched to non-initiators in each trial. The marginal hazard ratio between initiators and non-initiators was estimated for four acute outcomes: severe illness, hospitalization or death, hospitalization, and death; and the post-COVID condition or long COVID. Of 921,034 eligible “person-trials”, 74,449 were initiators and 846,585 were non-initiators of NMV-R treatment. Pooled across trials, the hazard for severe illness (HR: 0.76, 95% CI: 0.71 to 0.81), hospitalization or death (HR: 0.50, 95% CI: 0.44 to 0.57), hospitalization (sdHR: 0.52, 95% CI: 0.46 to 0.60), death (HR: 0.33, 95% CI: 0.21 to 0.51), and long-COVID (sdHR: 0.85, 95% CI: 0.77 to 0.95) were significantly lower among NMV-R initiators compared to non-initiators. Results further indicated larger associations between NMV-R and reduced risk of both acute and post-acute outcomes with early versus delayed NMV-R treatment initiation, and among unvaccinated versus vaccinated patient subgroups. NMV-R is overall effective at preventing the risk of severe acute outcomes including hospitalization and death, as well as long COVID. Results were robust across multiple sensitivity considerations. Not applicable.