QuestionWhat is the relative vaccine effectiveness of adjuvanted vs high-dose inactivated influenza vaccine against laboratory-confirmed influenza in US adults aged 65 years or older?FindingsThis cluster randomized crossover study of 429 595 individuals found that adjuvanted and high-dose influenza vaccines did not differ in effectiveness against laboratory-confirmed influenza during the 2023 to 2024 influenza season.MeaningConsistent with Advisory Committee on Immunization Practices recommendations, these results support the equivalency of adjuvanted and high-dose influenza vaccines for adults aged 65 years or older. This cluster randomized crossover study assesses the relative vaccine effectiveness of adjuvanted vs high-dose inactivated influenza vaccine against polymerase chain reaction-confirmed influenza in older US adults. ImportanceIn the US, adjuvanted or higher-dose influenza vaccines are preferentially recommended for annual use among adults aged 65 years or older. Adjuvanted and high-dose influenza vaccines have not been compared in a pragmatic randomized study.ObjectiveTo assess the relative vaccine effectiveness (rVE) of adjuvanted vs high-dose inactivated influenza vaccine against polymerase chain reaction (PCR)-confirmed influenza in older adults at Kaiser Permanente Northern California (KPNC).Design, Setting, and ParticipantsIn this cluster randomized crossover study, during the 2023 to 2024 influenza season, 65 KPNC facilities were cluster randomized such that approximately half of facilities administered adjuvanted and half high-dose influenza vaccine on the first week of the vaccination season (and thereafter every facility crossed over and alternated formulations weekly). Using Cox proportional hazards regression on a calendar time scale, the rVE of adjuvanted vs high-dose vaccine was estimated for each outcome as 1 minus the hazard ratio, adjusted for age, sex, race and ethnicity, comorbidities, and health care utilization. Study participants included all adults 65 years or older who were vaccinated with adjuvanted or high-dose inactivated influenza vaccine during routine care at a KPNC facility between August 17, 2023, and April 16, 2024.ExposuresAdjuvanted or high-dose inactivated influenza vaccine receipt during the 2023 to 2024 influenza season. Individuals were considered vaccinated 14 days after immunization.Main Outcomes and MeasuresThe primary outcome was PCR-confirmed influenza in any clinical setting. Secondary outcomes were PCR-confirmed influenza with hospitalization or emergency department visits and hospitalization for community-acquired pneumonia. Outcomes were assessed starting October 1, 2023, or 14 days after vaccination, whichever came later.ResultsThis study included 429 595 individuals from the 2023 to 2024 influenza season (mean [SD] age, 75 [7] years; 236 857 [55.1%] female; 86 287 [20.1%] Asian, 22 910 [5.3%] Black, 53 820 [12.5%] Hispanic, 1123 [0.3%] American Indian or Alaska Native, 2562 [0.6%] Pacific Islander, 252 709 [58.8%] White, 1638 [0.4%] multiracial, and 8546 [2.0%] unknown race), of whom 212 875 (49.6%) received adjuvanted and 216 720 (50.4%) received high-dose influenza vaccine. There were 836 cases of PCR-confirmed influenza (3.9 per 1000 persons) identified after adjuvanted and 867 cases (4.0 per 1000 persons) after high-dose vaccine. The rVE of adjuvanted compared with high-dose influenza vaccine was 1.5% (95% CI, -8.4% to 10.5%) against influenza, 9.1% (95% CI, -4.0% to 20.4%) against influenza with hospitalization or emergency department visits, and 1.0% (95% CI, -11.4% to 12.0%) against hospitalizations for community-acquired pneumonia.Conclusion and RelevanceIn the first season of a large, ongoing study in adults 65 years or older, adjuvanted and high-dose influenza vaccines did not differ in effectiveness against laboratory-confirmed influenza during the 2023 to 2024 influenza season. Consistent with Advisory Committee on Immunization Practices recommendations, these results support the equivalency of adjuvanted and high-dose influenza vaccines for adults 65 years or older.Trial RegistrationClinicalTrials.gov Identifier: NCT06029933

Studies reported elevated risk of immune thrombocytopenia (ITP) after the first dose of a measles-containing vaccine (MCV), including combined measles, mumps, and rubella vaccines, with varicella (MMRV) or without (MMR). Whether risk is also elevated after the second MCV dose is not fully understood. The objective of the study was to evaluate whether MCV administered between ages 4-6 years (typically second dose) is associated with increased risk of ITP. We conducted a retrospective study from 2000 through 2022 at 8 integrated healthcare systems within the Vaccine Safety Datalink. We included children who received their MCV between ages 4–6 years and were members of their health system at least 180 days prior to vaccination through 181 days after vaccination. Potential ITP cases were identified using International Classification of Diseases (ICD) 9th and 10th Revision codes 287.31 and D69.3 and presence of platelet count < 100,000/µL. These potential cases were then confirmed by medical record review. We compared the risk of ITP during days 15–28 (primary risk interval) and 1–42 (secondary risk interval) after vaccination with the risk during days 57–181 after vaccination (comparison interval). We used an exact binomial model to estimate relative risks and 95% confidence intervals (CI). Analyses were conducted for any MCV and separately by MMRV and MMR. Among 60 chart-confirmed ITP cases, 4 were confirmed during the 15–28-day risk interval, 19 were confirmed during the 1–42-day risk interval and 41 during the 57–181-day comparison interval. Compared with the comparison interval, the relative risk (RR) of ITP following any MCV was 0.93 (95% CI 0.27–2.56) during the 15–28-day risk interval and 1.16 (95% CI:0.57–2.24) during the 1–42-day risk interval. Compared with the comparison interval, the RR of ITP during the 15–28-day risk interval was 1.53 (95% CI 0.34–5.04) after MMRV and 0.43 (95% CI 0.02–2.74) after MMR. The RR of ITP during the 1–42-day risk interval was 1.44 (95% CI 0.58–3.33) after MMRV and 0.82 (95% CI 0.25–2.42) after MMR. The numbers were too small to compare RR by MCV type for the 15-28-day risk interval. Among children aged 4–6 years, MCVs were not associated with increased risk of ITP. Risk did not vary by MCV type. Ousseny Zerbo, PhD, Centers for Disease Control and Prevention: Grant/Research Support|Moderna: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support Stephanie Irving, MHS, Westat: Grant/Research Support Bruno Lewin, MD, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health: Grant/Research Support Malini B. DeSilva, MD, MPH, Centers for Disease Control and Prevention Vaccine Safety Datalink: Grant/Research Support|Westat: Grant/Research Support Maria Sundaram, PhD, MSPH, GSK: Grant/Research Support Nicola P. Klein, MD, PhD, AstraZeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support

Background:This descriptive seroepidemiology study characterized group B Streptococcus (GBS) capsular antibody levels in pregnant individuals and their newborns. Methods:Healthy US and South African ≥18-year-olds at ≥34 weeks of pregnancy were enrolled. Exploratory analyses evaluated GBS serotype-specific (Ia, Ib, II, III, IV, and V) anticapsular polysaccharide (CPS) immunoglobulin G (IgG) geometric mean concentrations (GMCs) before and at delivery and in cord blood; newborn-to-maternal transplacental transfer ratios were determined. Results:We enrolled 722 maternal (United States, n = 273; South Africa, n = 449) and 592 newborn participants (n = 251; n = 341). Maternal GBS anti-CPS IgG GMCs were similar before and at delivery. A trend for higher GMCs (serotypes Ia, Ib, II, and III) among South African compared with US maternal participants was seen. As in maternal participants, GMCs for serotypes Ia and III trended higher among South African compared with US newborns. Mean transplacental transfer ratios were higher for US newborn-maternal pairs compared with South African dyads. Transplacental transfer ratios for serotypes Ia and Ib were >1 for US pairs. Among US participants, there was a trend for higher transplacental transfer ratios among White versus Black participants. Maternal hypergammaglobulinemia (gamma globulin >1.35 g/dL) was observed in 23.8% of South African participants and in no US participants. Conclusions:Group B Streptococcus serotype-specific IgG GMCs varied by region and serotype; reasons for observed regional differences are likely multifactorial, including variations in baseline antibodies and transplacental transfer efficiency. Understanding these variations may inform efforts for maternal immunization strategies aimed at enhancing neonatal antibody concentrations.

Background:The 2024-25 influenza season was the most severe in the United States (US) since 2017- 18, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics. Methods:Using electronic healthcare encounter data from eight US states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024-April 2025 among children aged 6 months-17 years and adults aged ≥18 years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness (ARI) encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders. Results:Analyses included 108,618 encounters (5,764 hospitalizations and 102,854 ED/UC encounters) among children and 309,483 encounters (76,072 hospitalizations and 233,411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6,097/35,765) of cases versus 29.4% (21,449/72,853) of controls were vaccinated. Among adults, 28.2% (21,832/77,477) of cases versus 44.2% (102,560/232,006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41-60%) against influenza-associated hospitalizations and 54% (95% CI: 52-55%) against influenza- associated ED/UC encounters among children. VE was 43% (95% CI: 41-46%) against influenza- associated hospitalizations and 49% (95% CI: 47-50%) against influenza-associated ED/UC encounters among adults. Conclusions:Influenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024-25 influenza season. These findings support influenza vaccination as an important tool to reduce influenza-associated disease.

Test negative design studies allow for COVID-19 vaccine effectiveness (VE) estimation while minimizing selection bias from healthcare seeking and testing practices. However, failure to consider correlation between vaccination behaviors may result in biased COVID-19 VE estimates. Using different methods to account for potential correlation between COVID-19, influenza, and respiratory syncytial virus (RSV) vaccination status, we investigated variability in VE estimates of the 2023-2024 COVID-19 vaccine against COVID-19-associated emergency department and urgent care (ED/UC) encounters and hospitalizations during the 2023-2024 respiratory virus season. Data were leveraged from VISION, an electronic health record-based platform. VE estimates ≥7 days post vaccination did not increase by more than 5 percentage points against ED/UC encounters and 3 percentage points against hospitalizations when accounting for influenza and RSV vaccination status or excluding influenza and RSV positive controls. As the magnitude of this influence depends on season-specific factors, ongoing monitoring is warranted.

Respiratory syncytial virus (RSV) caused approximately 100,000-160,000 hospitalizations annually in adults aged ≥60 years in the United States (US) before RSV vaccine introduction. In 2023, two vaccines were recommended for prevention of severe RSV disease in adults aged ≥60 years using shared clinical decision making. In 2024, a third product was licensed, and all three available vaccines were recommended for all adults aged ≥75 years and for adults aged 60-74 years at increased risk of severe RSV disease. We assessed post-licensure vaccine effectiveness (VE) to inform future recommendations and public communications. VISION is a multi-site electronic health record-based study including >200 hospitals in the US. Adults aged ≥60 years hospitalized with RSV-like illness and tested for RSV were included. Cases had a positive molecular or antigen RSV test; controls had a negative molecular RSV test. Critical illness included admission to the intensive care unit or in-hospital death. VE against hospitalization and critical illness was calculated using a test negative design as (1-adjusted odds ratio) x 100% where the odds ratio compares odds of vaccination in cases and controls after adjusting for confounders. Results were stratified by time since RSV vaccination, age group, and immunocompromised status. Among 83,652 hospitalizations during October 2023-March 2024 and October 2024-March 2025, VE was 62% (95% CI: 56-67%, Table) against RSV-associated hospitalization, median 279 days after RSV vaccination. VE was 83% (95% CI: 73-89%) at 14-59 days after vaccination and 42% (95% CI: 30-53%) at least 1 year after vaccination (median 429 days). VE against RSV-associated critical illness was 69% (95% CI: 55-78%), median 277 days after vaccination. VE was similar by age group and among those with and without immunocompromising conditions. RSV vaccines are effective at preventing severe RSV and have the potential to reduce the burden of RSV-associated hospitalizations among older adults, although waning protection was apparent during the second season after vaccination. Ongoing monitoring of RSV VE is warranted to ensure vaccines are working as expected, to understand duration of protection, and to inform policy decisions. All Authors: No reported disclosures

Importance:The 2025-2026 COVID-19 vaccine, targeting JN.1 and JN.1-derived sublineages, became available in the US in September 2025. Objective:To assess the estimated interim effectiveness of 2025-2026 COVID-19 vaccines against medically attended COVID-19 among immunocompetent adults aged 18 years or older in the US. Design, Setting, and Participants:This case-control study used a test-negative design to investigate patient encounters captured in the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network, an electronic medical record-based network of health care systems (253 emergency departments/urgent cares [ED/UCs] and 179 hospitals in 7 states) from September 3, 2025, to December 31, 2025. Patient encounters with COVID-19-like illness and a molecular or antigen SARS-CoV-2 test 10 days before to 3 days after the encounter date were included. Exposure:2025-2026 COVID-19 vaccination regardless of prior COVID-19 vaccination. Main Outcomes and Measures:The main outcomes were COVID-19-associated ED/UC encounters and COVID-19-associated hospitalizations. Cases were defined as encounters with a positive molecular or antigen SARS-CoV-2 test and controls as encounters with a negative molecular SARS-CoV-2 test. The odds of 2025-2026 COVID-19 vaccination among cases and controls, adjusting for confounders, were compared and used to estimate vaccine effectiveness (VE) as (1 - adjusted odds ratio) × 100%. Results:In 85 725 ED/UC encounters among adults aged 18 years and older (51 841 [60%] aged 18-64 years; 51 775 female [60%]), 206 of 3941 cases (5%) and 9453 of 81 784 controls (12%) received a 2025-2026 COVID-19 vaccination. Estimated VE against COVID-19-associated ED/UC encounters was 50% (95% CI, 42%-57%; median [IQR] time since 2025-2026 COVID-19 vaccine dose receipt, 47 [27-69] days). In 26 073 hospitalizations with a COVID-19-like illness (17 530 [67%] aged ≥65 years; 13 985 female [54%]), 60 of 1022 cases (6%) received a 2025-2026 COVID-19 vaccination compared with 3080 of 25 051 controls (12%). Estimated VE against COVID-19-associated hospitalization was 55% (95% CI, 41%-66%; median [IQR] time since 2025-2026 COVID-19 vaccine dose receipt, 46 [26-68] days). Among patients aged 65 years or older, estimated VE against ED/UC encounters was 48% (95% CI, 37%-56%; median [IQR] time since dose receipt, 48 [27-69] days; 33 884 encounters) and against hospitalization was 53% (95% CI, 37%-65%; median [IQR] time since dose receipt, 46 [26-69] days; 17 530 hospitalizations). Conclusions and Relevance:In this study, receipt of 2025-2026 COVID-19 vaccination was associated with additional protection beyond existing immunity in adults against medically attended COVID-19, including ED/UC encounters and hospitalizations, compared with no receipt of a 2025-2026 vaccine dose. These findings suggest that adults can reduce their likelihood of severe COVID-19-associated outcomes by obtaining a 2025-2026 COVID-19 vaccination.

Importance:In the US, adjuvanted or higher-dose influenza vaccines are preferentially recommended for annual use among adults aged 65 years or older. Adjuvanted and high-dose influenza vaccines have not been compared in a pragmatic randomized study. Objective:To assess the relative vaccine effectiveness (rVE) of adjuvanted vs high-dose inactivated influenza vaccine against polymerase chain reaction (PCR)-confirmed influenza in older adults at Kaiser Permanente Northern California (KPNC). Design, Setting, and Participants:In this cluster randomized crossover study, during the 2023 to 2024 influenza season, 65 KPNC facilities were cluster randomized such that approximately half of facilities administered adjuvanted and half high-dose influenza vaccine on the first week of the vaccination season (and thereafter every facility crossed over and alternated formulations weekly). Using Cox proportional hazards regression on a calendar time scale, the rVE of adjuvanted vs high-dose vaccine was estimated for each outcome as 1 minus the hazard ratio, adjusted for age, sex, race and ethnicity, comorbidities, and health care utilization. Study participants included all adults 65 years or older who were vaccinated with adjuvanted or high-dose inactivated influenza vaccine during routine care at a KPNC facility between August 17, 2023, and April 16, 2024. Exposures:Adjuvanted or high-dose inactivated influenza vaccine receipt during the 2023 to 2024 influenza season. Individuals were considered vaccinated 14 days after immunization. Main Outcomes and Measures:The primary outcome was PCR-confirmed influenza in any clinical setting. Secondary outcomes were PCR-confirmed influenza with hospitalization or emergency department visits and hospitalization for community-acquired pneumonia. Outcomes were assessed starting October 1, 2023, or 14 days after vaccination, whichever came later. Results:This study included 429 595 individuals from the 2023 to 2024 influenza season (mean [SD] age, 75 [7] years; 236 857 [55.1%] female; 86 287 [20.1%] Asian, 22 910 [5.3%] Black, 53 820 [12.5%] Hispanic, 1123 [0.3%] American Indian or Alaska Native, 2562 [0.6%] Pacific Islander, 252 709 [58.8%] White, 1638 [0.4%] multiracial, and 8546 [2.0%] unknown race), of whom 212 875 (49.6%) received adjuvanted and 216 720 (50.4%) received high-dose influenza vaccine. There were 836 cases of PCR-confirmed influenza (3.9 per 1000 persons) identified after adjuvanted and 867 cases (4.0 per 1000 persons) after high-dose vaccine. The rVE of adjuvanted compared with high-dose influenza vaccine was 1.5% (95% CI, -8.4% to 10.5%) against influenza, 9.1% (95% CI, -4.0% to 20.4%) against influenza with hospitalization or emergency department visits, and 1.0% (95% CI, -11.4% to 12.0%) against hospitalizations for community-acquired pneumonia. Conclusion and Relevance:In the first season of a large, ongoing study in adults 65 years or older, adjuvanted and high-dose influenza vaccines did not differ in effectiveness against laboratory-confirmed influenza during the 2023 to 2024 influenza season. Consistent with Advisory Committee on Immunization Practices recommendations, these results support the equivalency of adjuvanted and high-dose influenza vaccines for adults 65 years or older. Trial Registration:ClinicalTrials.gov Identifier: NCT06029933.

Vaccine effectiveness (VE) studies are necessary to understand how well vaccines work in the real world. Many VE studies rely on health records to capture underlying medical conditions (UMCs) from a single acute respiratory illness- (ARI) associated encounter, which may bias VE if UMCs are not fully captured. We assessed capture of UMCs from a single acute encounter and a lookback period. Data were used from MarketScan® Treatment Pathways, a healthcare claims dataset, between September 1, 2023 – August 31, 2024. We included beneficiaries aged ≥18+ years with ≥1 inpatient or emergency department (ED) claim containing an ICD-10 code for ARI who had 3 years of continuous enrollment in a participating insurance plan prior to the date of their first ARI claim (i.e., index encounter). The prevalence of UMCs was calculated using ICD-10 codes from 1) the index encounter, and 2) the 1-year lookback period; and the difference was reported. Negative predictive value (NPV) with 95% exact binomial confidence intervals was calculated for identification of UMCs on the index encounter date, using the 1-year lookback period to define true negatives. Results were stratified by age group and encounter setting. Among 65,056 beneficiaries with ≥1 inpatient ARI event and 162,943 with ≥1 ED ARI event, the most prevalent UMC categories were cardiovascular, endocrine/metabolic, and respiratory (Tables 1-4). Among beneficiaries aged 18–64 years, NPV was < 80% for cardiovascular, endocrine/metabolic, and obesity categories; median difference in prevalence was 9.5 percentage points (pp) (min=0, max=30) (Tables 1 and 3). Among beneficiaries aged ≥65+ years, NPV was ≤80% for respiratory, cardiovascular, neurological and musculoskeletal, endocrine/metabolic, renal, and obesity categories; median difference in prevalence was 13.5 pp (min=0, max=52) (Tables 2 and 4). NPV, regardless of age, was > 90% for UMC categories with the lowest overall prevalence (i.e., cerebrovascular, hematologic, and underweight categories) (Tables 1-4). NPV was < 80% for common UMCs when identified using a single ARI encounter compared to a 1-year lookback period. Misclassification may influence VE estimates if UMCs are confounders in VE studies. Sara Y. Tartof, PhD, MPH, Centers for Disease Control and Prevention: Grant/Research Support Karthik Natarajan, PhD, Centers for Disease Control and Prevention: Grant/Research Support Stephanie Irving, MHS, Westat: Grant/Research Support Nicola P. Klein, MD, PhD, AstraZeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Shaun J. Grannis, MD, MS, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health NCATS: Grant/Research Support|National Institutes of Health NIMH: Grant/Research Support Toan Ong, PhD, Centers for Disease Control and Prevention via Westat: Grant/Research Support|Patent Title: Systems and Methods For Record Linkage: Patent Number: PCT/US2018/047961|PCORI: Travel Support|Regenstrief Institute: Advisor/Consultant|Regenstrief Institute: Travel Support Sarah W. Ball, MPH, ScD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support|Centers for Disease Control and Prevention, Contract #75D30121D12779: Grant/Research Support|Novavax: Grant/Research Support Malini B. DeSilva, MD, MPH, Centers for Disease Control and Prevention Vaccine Safety Datalink: Grant/Research Support|Westat: Grant/Research Support Ryan E. Wiegand, PhD, Merck & Co., Inc.: Stocks/Bonds (Public Company)|Sanofi S.A.: Stocks/Bonds (Public Company)

CDC recommends annual influenza vaccination for all persons aged ≥ 6 months. We estimated 2024–2025 seasonal influenza vaccine effectiveness (VE) against influenza–associated hospitalizations among adults.Figure 1.2024–2025 seasonal influenza vaccine effectiveness against influenza–associated hospitalizations among adults aged ≥ 18 years — VISION Network, October 2024–March 2025Abbreviations: CI = Confidence interval; ICU = Intensive care unit; IQR = Interquartile range; VE = vaccine effectiveness.a) Patients were considered vaccinated if they received ≥1 2024–2025 influenza vaccine dose ≥14 days before the index date, defined as the earlier date of the most recent influenza test and the hospital admission date.b) VE was estimated using multivariable logistic regression models comparing the odds of receipt of ≥1 2024–2025 influenza vaccine dose versus no dose among cases and controls. Models were adjusted for age, sex, race and ethnicity, calendar day, and healthcare system. Age and calendar day were treated as natural cubic splines with 4 degrees of freedom.c) Influenza A and B coinfections were excluded from influenza A and B case counts and from VE estimates against influenza A and B.d) Patients were considered immunocompromised if they had ≥1 ICD-10 discharge diagnosis code for any of the following conditions: hematologic malignancy, solid malignancy, bone marrow transplant, solid organ transplant, rheumatologic/inflammatory disorder, other intrinsic immunodeficiency condition, or HIV/AIDS.e) To estimate VE against ICU admission, cases were restricted to encounters with ICU admission and no in-hospital death. Data from the VISION Network were used to estimate influenza VE using a test-negative, case-control design. The analysis included hospitalizations among adults aged ≥ 18 years with ≥ 1 acute respiratory illness (ARI)–associated ICD-10 discharge diagnosis code from October 1, 2024–March 7, 2025 in six US healthcare systems. Cases were ARI hospitalizations with a positive molecular influenza test within 10 days before to 72 hours after the admission date. Controls were ARI hospitalizations with a negative molecular influenza test during the same interval. VE was estimated using multivariable logistic regression comparing the odds of receipt of ≥ 1 2024–2025 influenza vaccine dose versus no dose among cases and controls. VE models were adjusted for age, sex, race and ethnicity, calendar day, and healthcare system. A total of 31,338 ARI hospitalizations met inclusion criteria, including 4,969 cases and 26,369 controls (Figure). Overall VE against influenza–associated hospitalizations was 46% (95% CI=43–50%) with a median time since vaccination of 79 days (IQR=50–107). When stratified by time since vaccination, VE was 46% (95% CI=38–53%) at 14–59 days, 41% (95% CI=36–45%) at 60–119 days, and 9% (95% CI=-1 to 19%) at ≥ 120 days. VE was 46% (95% CI=42–50%) against influenza A and 65% (95% CI=41–80%) against influenza B. Among immunocompetent and immunocompromised adults, VE was 49% (95% CI=45–53%) and 33% (95% CI=23–42%), respectively. VE against influenza–associated intensive care unit (ICU) admission was 49% (95% CI=38–58%) and against in-hospital death was 48% (95% CI=31–62%). 2024–2025 seasonal influenza vaccines provided protection against influenza–associated hospitalizations among adults with evidence of decreased VE ≥ 120 days after vaccination. VE point estimates were higher against influenza B than against influenza A and among immunocompetent versus immunocompromised adults. VE against influenza–associated ICU admission and in-hospital death were similar to that against hospitalization. Zachary Weber, PhD, MS, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Duck-Hye Yang, PhD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Stephanie Irving, MHS, Westat: Grant/Research Support Sara Y. Tartof, PhD, MPH, Centers for Disease Control and Prevention: Grant/Research Support Nicola P. Klein, MD, PhD, AstraZeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Shaun J. Grannis, MD, MS, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health NCATS: Grant/Research Support|National Institutes of Health NIMH: Grant/Research Support Toan Ong, PhD, Centers for Disease Control and Prevention via Westat: Grant/Research Support|Patent Title: Systems and Methods For Record Linkage: Patent Number: PCT/US2018/047961|PCORI: Travel Support|Regenstrief Institute: Advisor/Consultant|Regenstrief Institute: Travel Support Sarah W. Ball, MPH, ScD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support|Centers for Disease Control and Prevention, Contract #75D30121D12779: Grant/Research Support|Novavax: Grant/Research Support Malini B. DeSilva, MD, MPH, Centers for Disease Control and Prevention Vaccine Safety Datalink: Grant/Research Support|Westat: Grant/Research Support Padma Kppolu, MPH, Westat: Grant/Research Support S. Bianca Salas, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Pfizer: Grant/Research Support Lina S. Sy, MPH, AstraZeneca: Grant/Research Support|Dynavax: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support Bruno Lewin, MD, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health: Grant/Research Support Richard Contreras, MS, Centers for Disease Control and Prevention: Grant/Research Support Ousseny Zerbo, PhD, Centers for Disease Control and Prevention: Grant/Research Support|Moderna: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support John R. Hansen, MPH, Centers for Disease Control and Prevention: Grant/Research Support Lawrence Block, MPH, MPA, Centers for Disease Control and Prevention: Grant/Research Support Karen B. Jacobson, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support William F. Fadel, PhD, Centers for Disease Control and Prevention: Grant/Research Support Catia Chavez, MPH, Westat: Grant/Research Support Adam Yates, PhD, Beehive Study: Grant/Research Support|Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Lindsey Kirshner, MPH, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Charlene E. McEvoy, MD, MPH, Astra Zeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|Department of Defense: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|National Institutes of Health: Grant/Research Support|PCORI: Grant/Research Support Karthik Natarajan, PhD, Centers for Disease Control and Prevention: Grant/Research Support

Importance:Antigenically drifted influenza A(H3N2) J.2.4.1 (subclade K) viruses predominated during the 2025-2026 Northern Hemisphere influenza season. Objective:To describe influenza activity and burden, characterize subclade K, evaluate susceptibility to influenza antivirals and postinfluenza vaccination antibodies, and estimate vaccine effectiveness. Design, Setting, and Participants:This surveillance study used multiple data sources, including (1) national surveillance of influenza-positive respiratory specimens collected by approximately 300 clinical laboratories and 100 public health laboratories from October 1, 2025, through March 14, 2026, a subset of which were further characterized; (2) serologic data of people who received 2025-2026 influenza vaccines; (3) influenza admissions data from the Influenza Hospitalization Surveillance Network (ie, 10% of US population) and the associated estimates of US burden; and (4) test-negative, case-control vaccine effectiveness estimates from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network. Exposures:Influenza infection, hospitalization, and vaccination. Main Outcomes and Measures:Outcomes included influenza virus type, subtype, and clade; antiviral susceptibility; immunogenicity; influenza-associated outpatient and emergency department visits, hospitalizations, and mortality; estimated influenza illnesses, hospitalizations, and death; and estimated vaccine effectiveness. Results:As of March 14, 2026, of the 55 318 influenza-positive respiratory specimens tested by public health laboratories, most (50 291 specimens [90.9%]) were influenza A, of which 40 779 (81.1%) were subtyped and 35 801 (87.8%) were A(H3N2). Of the 1754 characterized A(H3N2) viruses, most (1626 specimens [92.7%]) were subclade K. Postinfluenza vaccination neutralizing geometric mean antibody titers against subclade K were reduced 1.62 (95% CI, 1.29-2.02)-fold compared with the vaccine virus. All 1729 tested A(H3N2) viruses were sensitive to antivirals. Of the 27 881 recorded influenza hospitalizations, 15 426 (54.7%) were among female patients, and 15 051 (54.0%) were among patients aged 65 years or older. The estimated cumulative influenza-associated hospitalization rate was 80.0 per 100 000 which would correlate with estimates of between 28 000 000 to 49 000 000 illnesses, 360 000 to 740 000 hospitalizations, and 22 000 to 74 000 deaths in the US during the 2025-2026 season. Adjusted interim vaccine effectiveness estimates against influenza-associated emergency department or urgent care encounters and hospitalizations were 35% (95% CI, 33%-38%) and 27% (95% CI, 21%-34%), respectively. Conclusions and Relevance:This surveillance study found that while antigenically drifted viruses predominated and caused substantial morbidity and mortality, influenza vaccines were associated with a reduced risk of influenza among those who were vaccinated, and recommended antivirals remained effective.

BACKGROUND:SARS-CoV-2 vaccination during pregnancy reduces COVID-19 risk in infancy. Whether maternal vaccination before pregnancy similarly protects infants against COVID-19 is unknown. METHODS:We examined the effectiveness of maternal messenger RNA SARS-CoV-2 vaccination before and during pregnancy in preventing COVID-19 in infants aged 0-6 months born between July 1, 2021, and June 30, 2023, at Kaiser Permanente Northern California. Maternal vaccination status was categorized as vaccinated during pregnancy, during a prepregnancy interval (0-<3, 3-<6, 6-12, and >12 months prepregnancy), or unvaccinated. Secondary analyses examined the effectiveness of vaccination by trimester. COVID-19 was defined by positive SARS-CoV-2 PCR result or diagnostic code, and COVID-19-related hospitalizations were confirmed by medical record review. Vaccine effectiveness (VE) was examined by Cox regression models adjusted for maternal and infant characteristics, calculated as (1 - hazard ratio) × 100%. RESULTS:Among 78 644 infants, 3648 (4.6%) had COVID-19 infection and 76 (0.1%) experienced COVID-19-related hospitalization before age 6 months. For the 4 prepregnancy vaccination intervals, estimates for VE against COVID-19 infection ranged from -14.9% (95% CI, -32.8% to 0.5%) for less than 3 months prepregnancy to 23.6% (-14.3% to 49%) for more than 12 months prepregnancy. VE anytime during pregnancy was 7.5% (-2% to 16.2%) against infant COVID-19 infection and 52.9% (11.1%-75.1%) against infant COVID-19-related hospitalization. Effectiveness of third-trimester vaccination was 19.2% (8.6%-28.6%) against infant COVID-19 infection and 64.6% (12.3%-85.7%) against infant COVID-19-related hospitalizations. CONCLUSION:Maternal vaccination during the third trimester was protective against infant COVID-19 infections. Maternal vaccination during pregnancy, particularly during the third trimester, was effective against infant COVID-19-related hospitalizations. Vaccination before pregnancy did not protect infants.

OBJECTIVE:To assess adverse pregnancy and birth outcomes after bivalent prefusion F subunit-based respiratory syncytial virus vaccine (RSVpreF) vaccination during the first season of availability. METHODS:This was a target trial emulation study including eight health systems across eight states (California, Oregon, Washington, Colorado, Maryland, Virginia, Minnesota, and Wisconsin) and Washington, DC, in the Vaccine Safety Datalink (VSD). We included pregnant patients aged 16-49 years who had enrolled at a VSD site between September 22, 2023, and February 29, 2024. Exposure was defined as receipt of RSVpreF vaccination between 32 and less than 37 weeks of gestation. Outcomes included preterm birth (PTB), stillbirth, small-for-gestational-age (SGA) birth weight, and hypertensive disorders of pregnancy (HDP) assessed with electronic health record data. Stillbirth cases were confirmed through chart review. Pregnant patients exposed to RSVpreF vaccines were matched 1:1 to unexposed pregnant patients at the gestational week of vaccination by propensity to be vaccinated and VSD site. Unexposed pregnant patients were assigned an index date equivalent to the gestational day of vaccination for their vaccinated match. If the unvaccinated match was subsequently vaccinated, the pair was censored. We report adverse event risks and adjusted risk ratios (aRRs) with corresponding 95% CIs adjusted for nulliparity using a log binomial model with robust variance. RESULTS:We identified 13,966 pregnant patients who received the RSVpreF vaccine. A higher percentage of nulliparous patients were in the vaccinated group (46.4%) compared with the unvaccinated group (38.7%). Comparing RSVpreF vaccinated pregnant patients and their unvaccinated matches, rates of PTB (4.0% vs 4.5%, respectively; aRR 0.90, 95% CI, 0.80-1.00), stillbirth (0.79/1,000 and 0.72/1,000; aRR 0.99, 95% CI, 0.41-2.36), and SGA birth weight (6.8% and 6.5%; aRR 1.02, 95% CI, 0.92-1.12) did not significantly differ. The rate of any HDP among RSVpreF vaccinated patients was 17.3% vs 15.0% among their unvaccinated matches (aRR 1.13, 95% CI, 1.07-1.19). CONCLUSION:Initial prenatal RSVpreF safety surveillance shows a largely favorable safety profile. Although we identified a small but statistically significant increased risk for HDP after RSVpreF vaccination, there was no increased risk for PTB, SGA birth weight, or stillbirth.

On June 26, 2024, the CDC updated respiratory syncytial virus (RSV) vaccine recommendations to a single dose of RSV vaccine for all adults aged ≥ 75 years and adults aged 60-74 years with increased risk of severe RSV disease. Using electronic health record (EHR) data from the VISION platform, we described characteristics of patients testing negative for RSV who did and did not receive an RSV vaccine and assessed factors associated with RSV vaccine receipt.Figure 1:Characteristics associated with receipt of respiratory syncytial virus (RSV) vaccination among test-negative patients with an emergency department (ED) encounter for RSV-like illness (RLI) during the 2024-2025 season in the VISION network, N=23,403 patientsFigure 2:Characteristics associated with receipt of respiratory syncytial virus (RSV) vaccine among test-negative patients with an inpatient encounter for RSV-like illness (RLI) during the 2024-2025 season in the VISION network, N=25,020 patients Patients with ≥ 1 emergency department (ED) or inpatient encounter at any of 6 participating health systems in 8 states with RSV-like illness (RLI) during October 1, 2024-March 31, 2025 were included. Vaccination status was ascertained from EHR, state and city immunization information systems, and medical claims. Patients who tested positive for SARS-CoV-2 or influenza viruses at the same RLI encounter were excluded. Patient age, sex, race and ethnicity, Medicaid status, number of underlying medical conditions, month of medical encounter, and documented receipt of COVID-19 or influenza vaccines were evaluated as covariates when assessing the odds of vaccination. The best fitting multivariable logistic regression models using Bayesian Information Criterion were chosen. Among 48423 included patients, 2113 (4.4%) had documented RSV vaccine receipt. The odds of RSV vaccination differed by site and increased with calendar time and age. Compared to patients aged 60-64 years, those aged ≥ 75 years were more likely to have received an RSV vaccine (ED: aOR: 3.6, 95%CI: 2.7-4.8, Figure 1; inpatient: aOR: 2.3, 95%CI: 1.7-3.0, Figure 2). Receipt of both influenza and COVID-19 vaccine within the same season had the strongest association with RSV vaccination in both the ED (aOR: 14.88, 95%CI: 11.87-18.89, Figure 1) and hospital setting (aOR: 20.04, 95%CI: 16.20-25.03, Figure 2). Receipt of other respiratory viral vaccines was the strongest indicator of RSV vaccination in the 2024-2025 RSV season in patients testing negative for RSV among all demographic and clinical characteristics considered. RSV vaccination was lower among those aged 60-64 years than older patients. These findings inform future methods to estimate vaccine effectiveness and inform policy implementation. Gabriela Vazquez-Benitez, PhD, MSc, AbbVie: research funding not related to this study|Sanofi: Grant funding for other research not related to this study Stephanie Irving, MHS, Westat: Grant/Research Support Nicola P. Klein, MD, PhD, AstraZeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Shaun J. Grannis, MD, MS, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health NCATS: Grant/Research Support|National Institutes of Health NIMH: Grant/Research Support Toan Ong, PhD, Centers for Disease Control and Prevention via Westat: Grant/Research Support|Patent Title: Systems and Methods For Record Linkage: Patent Number: PCT/US2018/047961|PCORI: Travel Support|Regenstrief Institute: Advisor/Consultant|Regenstrief Institute: Travel Support Sarah W. Ball, MPH, ScD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support|Centers for Disease Control and Prevention, Contract #75D30121D12779: Grant/Research Support|Novavax: Grant/Research Support Jingran Cao, MS, Sanofi Pasteur: Grant/Research Support Charlene E. McEvoy, MD, MPH, Astra Zeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|Department of Defense: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|National Institutes of Health: Grant/Research Support|PCORI: Grant/Research Support Ousseny Zerbo, PhD, Centers for Disease Control and Prevention: Grant/Research Support|Moderna: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support John R. Hansen, MPH, Centers for Disease Control and Prevention: Grant/Research Support Lawrence Block, MPH, MPA, Centers for Disease Control and Prevention: Grant/Research Support Karen B. Jacobson, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support William F. Fadel, PhD, Centers for Disease Control and Prevention: Grant/Research Support Catia Chavez, MPH, Westat: Grant/Research Support Karthik Natarajan, PhD, Centers for Disease Control and Prevention: Grant/Research Support Ryan E. Wiegand, PhD, Merck & Co., Inc.: Stocks/Bonds (Public Company)|Sanofi S.A.: Stocks/Bonds (Public Company)

Background:The 2024-2025 influenza season was the most severe in the United States (US) since 2017-2018, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics. Methods:Using electronic healthcare encounter data from 7 VISION sites in 8 US states, we evaluated influenza VE against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024 to April 2025 among children aged 6 months-17 years and adults aged ≥18 years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders. Results:Analyses included 108 618 encounters (5764 hospitalizations and 102 854 ED/UC encounters) among children and 309 483 encounters (76 072 hospitalizations and 233 411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6097/35 765) of cases versus 29.4% (21 449/72 853) of controls were vaccinated. Among adults, 28.2% (21 832/77 477) of cases versus 44.2% (102 560/232 006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41%-60%) against influenza-associated hospitalizations and 54% (95% CI: 52%-55%) against influenza-associated ED/UC encounters among children. VE was 43% (95% CI: 41%-46%) against influenza-associated hospitalizations and 49% (95% CI: 47%-50%) against influenza-associated ED/UC encounters among adults. Conclusions:Influenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024-2025 influenza season. These findings support influenza vaccination as an important tool to reduce influenza.

BACKGROUND AND OBJECTIVES:In this study, we evaluated whether maternal COVID-19 and influenza vaccination status during pregnancy was associated with infant vaccine coverage. METHODS:This observational cohort study included infants 6 to 13 months old born at Kaiser Permanente Northern California between August 2021 and March 2024 and their mothers. We used the Kaplan-Meier approach to estimate the cumulative probability of infants receiving at least one dose of a vaccine and Cox models to estimate the hazard ratio of infant vaccination by maternal vaccination status adjusted for covariates. Mothers were considered vaccinated if they received a COVID-19 or influenza vaccine from 12 months before pregnancy onset date to 3 months postpartum; those who did not receive a vaccine in this window were considered unvaccinated. RESULTS:The study included 82 533 mother-infant pairs. Infants in the study had a 23.4% probability of receiving a COVID-19 vaccine and 66.2% probability of receiving an influenza vaccine in the first year of life. Infants whose mother received a COVID-19 vaccine during pregnancy were 9.65 (95% CI, 9.06-10.27) times more likely to be vaccinated against COVID-19 and those whose mother received an influenza vaccine during pregnancy were 3.67 (95% CI, 3.58-3.77) times more likely to be vaccinated against influenza than those whose mother was not vaccinated. Vaccination before pregnancy or during postpartum was also associated with infant vaccination compared with no maternal vaccination. CONCLUSIONS:Maternal vaccination for respiratory vaccines was strongly associated with infant vaccination; increasing maternal vaccine coverage may improve infant coverage.

Abstract Background The Vaccine Safety Datalink (VSD) detected a statistical signal for ischemic events (ischemic stroke or transient ischemic attack) following bivalent mRNA COVID-19 vaccination through prospective surveillance during 2022-2023. Although multiple studies from other surveillance systems and countries reported no increased risk, important methodological limitations remained. This U.S. study addressed those limitations by evaluating the ischemic stroke risk following bivalent mRNA COVID-19 vaccination, influenza vaccination, and their same-day coadministration using event-dependent self-controlled case series (SCCS) design. Methods Study outcomes included first-ever ischemic stroke (primary outcome), first-in-1-year ischemic stroke (secondary outcome), and ischemic events (exploratory outcomes), identified using ICD-10-CM codes in inpatient and emergency department settings during September 1, 2022–March 31, 2023, among individuals aged ≥12 years across eight VSD sites. Analyses were conducted separately for Pfizer-BioNTech and Moderna bivalent vaccines, with relative incidences (RI) and 95% confidence intervals (CI) estimated for 1–21-day and 1–42-day risk intervals, using person-time outside these intervals as the control period. Subgroup analyses were performed by age group (12–64, >65 years) and history of documented SARS-CoV-2 infection. Results A total of 6,510 first-ever ischemic strokes were identified among more than 6.8 million participants. Among recipients of Pfizer-BioNTech bivalent COVID-19 and influenza vaccines, no statistically significant increased risk of first-ever ischemic stroke was observed following bivalent COVID-19 vaccination (RI = 0.94; 95% CI: 0.63–1.41), influenza vaccination (RI = 0.95; 95% CI: 0.82–1.10), or same-day coadministration (RI = 1.15; 95% CI: 0.88–1.49) within 1– 21-day risk intervals; findings were similar for 1–42-day intervals. Comparable null results were observed for Moderna vaccines and across all subgroups, secondary, and exploratory outcomes. Conclusion No increased risk of ischemic stroke was found following bivalent mRNA COVID-19 vaccination, influenza vaccination, or their coadministration in this multi-site SCCS study. These findings are consistent with previous studies and underscore the importance of continued vaccine safety monitoring. Highlights We evaluated ischemic stroke risk after bivalent mRNA COVID-19 vaccination, influenza vaccination, and their coadministration. No increased risk of ischemic stroke was observed within 1–21 or 1–42 days following these vaccination exposures. Findings were consistent across vaccine type, age group, and prior SARS-CoV-2 infection status. These results support the safety of bivalent mRNA COVID-19 vaccines with respect to ischemic stroke.

In the United States, annual influenza vaccination has been recommended for all persons aged ≥6 months, including during the 2025-26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness-associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks during the 2025-26 influenza season, using a test-negative case-control design. Among children and adolescents aged <18 years, VE was 38%-41% against influenza outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%-34% against influenza outpatient visits and 30% against influenza-associated hospitalization. Among children and adolescents, VE against influenza A ranged from 37% (against outpatient visits) to 42% (against hospitalization) across settings; among adults, VE against influenza A ranged from 30% (against hospitalization) to 34% (against outpatient visits) across settings. Among children and adolescents, VE against influenza A(H3N2)-associated outpatient visits was 35% and against influenza A(H3N2)-associated hospitalization was 38%. VE against influenza B outpatient visits ranged from 45%-71% among children and adolescents and was 63% among adults. Other estimates of VE were not statistically significant or were not reportable. Although interim influenza VE is lower during the 2025-26 influenza season than it was during recent influenza seasons, these findings demonstrate that influenza vaccination still provides protection against influenza. CDC recommends influenza vaccination; U.S. influenza vaccines remain available for persons aged ≥6 months.

BACKGROUND:Rotavirus vaccines (RVs) are coadministered in the United States with diphtheria-tetanus-acellular pertussis (DTaP) vaccines but have age restrictions for the first and last doses. We examined how delays in preventive care visits for vaccination affected RV initiation and series completion. METHODS:We compared the timeliness of DTaP vaccination relative to RV in children born January 1, 2018 to June 30, 2023 across 8 US health systems. Adjusted risk ratios (aRRs) were estimated using modified Poisson regression to identify risk factors for delayed DTaP vaccination and no RV vaccination. RESULTS:Among 391 892 children who initiated DTaP, 12 546 (3.2%) did not initiate RV. Of these, 7721 (61.5%) children had delayed DTaP initiation and were age-ineligible for RV at the time of DTaP initiation. Children who became eligible for RV during the early stage of the COVID-19 pandemic (March to May 2020) had a higher risk of delayed DTaP and no RV initiation (aRR = 2.20; 95% CI, 1.98-2.45), as did children with fewer than 5 primary care visits within the first year of life (aRR = 4.03; 95% CI, 3.81-4.26), and Medicaid recipients (aRR = 2.34; 95% CI, 2.23-2.45). Similar factors were associated with failure to complete the RV series due to age restrictions. CONCLUSIONS:Age restrictions may have contributed to lack of RV initiation and series completion in this cohort. Public health strategies tailored to populations at risk for delayed vaccination may be needed to promote timely administration of RV.

Importance:Vaccine effectiveness (VE) estimates are needed to monitor the effect of updated COVID-19 vaccinations. Objective:To assess the effectiveness of 2024-2025 COVID-19 vaccines against medically attended COVID-19 among adults 18 years and older in the US. Design, Setting, and Participants:This case-control study with a test-negative design included patient encounters with a COVID-19-like illness discharge diagnosis code and a molecular or antigen SARS-CoV-2 test within 10 days before to 3 days after the encounter date, from September 5, 2024, to September 2, 2025. Encounters were captured in VISION (Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network), a multisite, electronic medical record-based network of health care systems, including 381 emergency department/urgent care (ED/UC) departments and 246 hospitals in 6 states. Exposure:Vaccination with a 2024-2025 COVID-19 vaccine formulation (approved by the US Food and Drug Administration in August 2024) in the previous 7 to 299 days. Main Outcomes and Measures:Outcomes were COVID-19-associated ED/UC encounters, COVID-19-associated hospitalization, and COVID-19-associated critical illness (hospitalization with an intensive care unit admission or in-hospital death). Encounters with a positive molecular or antigen SARS-CoV-2 test result were classified as cases, and encounters with a negative molecular SARS-CoV-2 test result were classified as controls. The odds of 2024-2025 COVID-19 vaccination were compared among cases and controls, adjusting for confounders, with estimated VE calculated as (1 - adjusted odds ratio) × 100%. Results:In 333 262 eligible ED/UC encounters (median [IQR] age of patients, 54 [35-72] years; 60% female) and 97 663 eligible hospitalizations among immunocompetent adults 18 years and older (median [IQR] age of patients, 72 [59-81] years; 53% female), estimated VE was 26% (95% CI, 23%-29%) against COVID-19-associated ED/UC encounters, 35% (95% CI, 30%-40%) against COVID-19-associated hospitalization, and 41% (95% CI, 28%-51%) against COVID-19-associated critical illness 7 to 299 days after vaccination. Among immunocompetent adults 65 years and older (122 663 ED/UC encounters and 63 958 hospitalizations), estimated VE was 26% (95% CI, 22%-30%) against COVID-19-associated ED/UC encounters, 35% (95% CI, 29%-40%) against COVID-19-associated hospitalization, and 41% (95% CI, 28%-52%) against COVID-19-associated critical illness 7 to 299 days after vaccination. Among 32 629 hospitalizations in immunocompromised adults 18 years and older, estimated VE against COVID-19-associated hospitalization was 24% (95% CI, 13%-34%). VE estimates waned with more time since vaccination. Conclusions and Relevance:In this test-negative case-control study, 2024-2025 COVID-19 vaccination was associated with reduced likelihood of medically attended COVID-19-associated outcomes among immunocompetent and immunocompromised adults, highlighting the importance of adults receiving recommended COVID-19 vaccinations.