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.

BACKGROUND:On 7 March 2024, the Chicago Department of Public Health was notified of a positive measles test in a resident of a shelter housing >2100 persons. We estimated the effectiveness of measles-mumps-rubella vaccine (MMR) administered during the outbreak to guide its use as an acute intervention. METHODS:We used Pearson χ2 tests to compare unadjusted attack rates (ARs) by age group, number of days exposed, and sex. We estimated adjusted hazard ratios (aHRs) using time-dependent Cox proportional hazards regression models to assess the association between time-varying MMR dose status and the outcome of laboratory-confirmed measles; the final model was adjusted for time-varying exposure to measles virus and age group. We estimated risk-adjusted vaccine effectiveness (VE) as VE = (1 - aHR) × 100. RESULTS:Measles was diagnosed in 52 of 2243 (2.3%) residents who resided in the shelter for ≥1 day during 22 February-4 April 2024. ARs were highest among children aged <6 months (57.1%) and 6-11 months (55.6%) and among residents who were exposed for 8-13 days (10.1%). ARs did not differ by sex. Estimated 1-dose VE was 70% (95% confidence interval [CI], 28%-88%) and estimated ≥2-dose VE was 72% (95% CI, 21%-90%). CONCLUSIONS:This study provided a unique opportunity to evaluate MMR VE in a contemporary outbreak setting with a high force of infection and could guide future responses in similar congregate settings. MMR was effective at preventing measles among shelter residents. Public health efforts that prioritize vaccinating persons without ≥2 MMR doses remain critical for limiting transmission.

We evaluated effectiveness of respiratory syncytial virus (RSV) vaccines against RSV-associated thromboembolic events among community-dwelling Medicare fee-for-service beneficiaries >65 years of age in the United States enrolled during October 1, 2023-March 30, 2024. RSV vaccines protected against RSV-associated thromboembolic events (effectiveness 79% [95% CI 74%-83%]) in the same season as vaccine receipt.

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:Vaccine effectiveness (VE) estimates are needed to determine the effectiveness of respiratory syncytial virus (RSV) vaccinations during their first season of availability among populations at high risk for severe RSV. Objective:To assess RSV VE against RSV-associated outcomes for nursing home residents. Design, Setting, and Participants:This retrospective cohort study of Medicare fee-for-service beneficiaries used electronic medical claims data from September 10, 2023, to March 30, 2024. A cohort was created for each outcome: an RSV-associated hospitalization cohort; an RSV-associated death cohort; a severe RSV-associated outcome cohort; and an RSV-associated thromboembolic event cohort. To be eligible for inclusion in a cohort, a Medicare fee-for-service beneficiary must be aged 65 years or older, reside in a US nursing home during the study period for at least 1 day, have continuous enrollment in Medicare Parts A and B (365 days prior to the index date), and have continuous enrollment in Part D (beginning on June 21, 2023). Exposure:RSV vaccination. Main Outcomes and Measures:Outcomes were RSV-associated hospitalization, RSV-associated death, severe RSV-associated outcomes (intensive care unit or critical care unit admission, medical ventilator use, or RSV-associated death), and RSV-associated thromboembolic event. RSV diagnoses and outcome definitions were based on claims with relevant International Classification of Diseases and Related Health Problems, Tenth Revision codes. RSV vaccine doses were determined from Medicare Part D claims using the National Drug Code Directory. Hazard ratios (HRs) from multivariable Cox proportional hazards models compared the times to first outcomes among RSV vaccinated beneficiaries and unvaccinated beneficiaries. VE was calculated as (1-HR) × 100%. Results:Of 597 430 included Medicare beneficiaries (66% female; median age, 82 [IQR, 75-88] years), RSV VE against RSV-associated hospitalizations was 73% (95% CI, 65%-79%). Among beneficiaries aged 65 to 74 years VE was 60% (95% CI, 35%-76%), 75% (95% CI, 67%-82%) among beneficiaries 75 years or older, 67% (95% CI, 55%-76%) among short-stay residents (<100 cumulative days), and 80% (95% CI, 68%-87%) among long-stay residents (≥100 cumulative days). VE against RSV-associated death was 56% (95% CI, 39%-69%), VE against severe RSV-associated outcomes was 59% (95% CI, 44%-70%), and VE against RSV-associated thromboembolic events was 66% (95% CI, 44%-79%). Conclusions and Relevance:In this study, in the first season of availability, RSV vaccines were associated with improved RSV-associated outcomes among US Medicare beneficiaries residing in nursing homes.

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)

Since June 2024, CDC’s Advisory Committee on Immunization Practices (ACIP) has recommended a single dose of RSV vaccination for all adults aged ≥75 years and for adults aged 60–74 years who are at increased risk of severe RSV disease. RSV vaccines are effective in preventing RSV-associated hospitalization, with the potential to prevent tens of thousands of annual hospitalizations and deaths in older adults. However, certain adults aged < 60 years are also at increased risk of severe illness caused by RSV. In considering RSV vaccination for adults aged 50–59 years, ACIP reviewed risk of RSV-associated hospitalization among adults with and without chronic medical conditions, differential risk by race and ethnicity, duration of vaccine protection and potential need for revaccination, risk of Guillain-Barre syndrome (GBS) associated with subunit RSV vaccines, national vaccine uptake, societal costs of the vaccination program, complexity of changes to the immunization schedule, and challenges in implementing a risk-based recommendation in retail pharmacies, where most older adults have received RSV vaccination. ACIP members discussed variability in individual-level risk of severe RSV disease in persons with specific chronic conditions and the balance of benefits and risks of RSV vaccination in adults aged < 60 years, who generally experience lower risk of severe outcomes from RSV infection compared with older adults. Members were concerned about the disproportionate burden of severe RSV disease and higher prevalence of chronic medical conditions among Black adults in the U.S., particularly in the 50–59-year age group. Members expressed a need for more data to inform optimal timing of revaccination after vaccine-induced immunity wanes, which is particularly important for younger adults with longer remaining life expectancy. Overall, Committee members thought that the public health benefits of RSV vaccination outweighed risks for adults aged 50–59 years with certain chronic medical conditions. On April 16, 2025, ACIP recommended a single dose of RSV vaccine for these adults using the same qualifying risk conditions used for adults aged 60–74 years. ACIP plans to consider RSV vaccine recommendations for adults aged 18–49 years at a future public meeting. Helen Y. Chu, MD, MPH, Roche: Advisor/Consultant|Vir: Advisor/Consultant

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)

OBJECTIVE:In 2023, 2 products, a long-acting monoclonal antibody (nirsevimab) and maternal respiratory syncytial virus (RSV) vaccination, were recommended in the United States to prevent severe RSV disease among infants in their first RSV season. Low uptake during the 2023 to 2024 RSV season limited effectiveness estimates. We estimated nirsevimab and maternal RSV vaccine effectiveness against RSV-associated emergency department (ED) encounters and hospitalization among US infants during the 2024 to 2025 RSV season, when uptake was higher. METHODS:We used electronic health record data from 5 health care systems in test-negative analyses of ED encounters and hospitalizations with RSV-like illness during October 1, 2024 to March 31, 2025, among infants in their first RSV season. Nirsevimab and maternal RSV vaccine effectiveness were estimated by comparing RSV-positive with RSV-negative encounters with respect to immunization status in separate logistic regression models adjusted for age, race and ethnicity, sex, calendar day, and geographic region. RESULTS:Among 3531 ED encounters and 470 hospitalizations included in the nirsevimab analyses, nirsevimab effectiveness against RSV-associated ED encounters and hospitalization was 62% (95% CI: 54-68) and 77% (95% CI: 61-87), respectively. Among 810 ED encounters and 187 hospitalizations included in the maternal RSV vaccine analyses, vaccine effectiveness against RSV-associated ED encounters and hospitalization was 49% (95% CI: 26-65) and 82% (95% CI: 54-93), respectively. CONCLUSION:Nirsevimab and maternal RSV vaccination were effective against RSV-associated ED encounters and hospitalization among infants in their first RSV season. As uptake increases and additional products are recommended, monitoring infant RSV immunization effectiveness remains important.

IntroductionElectronic health record (EHR)-based research often relies on structured data elements, such as ICD-10-CM and CPT codes, to identify clinical diagnoses and procedures. However, some information, such as the administration of immunizations, may be captured more reliably in the text-based narrative sections of the patient's record. We developed a rule-based natural language processing (NLP) algorithm to identify the administration of immunizations for COVID-19, influenza, and RSV using a combination of synthetic and publicly available data.MethodsAfter applying standard NLP processing techniques to clean and standardize the text, we implemented a multi-stage, rule-based algorithm. We applied a dictionary of general keywords to identify potential immunizations, and a set of specific keywords, which leveraged grammatical dependencies in the text, to increase accuracy. We implemented additional rules to account for negation and immunization recommendations. The algorithm was applied to a sample of 20,000 patients from the study population. We measured performance by conducting a manual review of 400 individual notes and assessing concurrence with structured data, using precision and recall as evaluation metrics.ResultsIn the first evaluation, which compared the performance of the algorithm with an independent test dataset using manual clinical review, precision was 71% and recall was 97% for COVID-19 immunization; 91% and 92% for Influenza; and 57% and 96% for RSV. In a second evaluation using structured data as the gold standard (i.e., ICD-10-CM, CPT, and CVX codes), precision was 72% and recall was 9% for COVID-19 immunization; 71% and 12% for Influenza; and for RSV, precision was 78% and recall was 10%.DiscussionWe demonstrated the effectiveness of NLP methods in identifying immunizations from EHR. High precision and recall for COVID-19 and influenza immunizations suggest that the algorithm can effectively identify immunization references when they are present in the text; however, low recall when compared to the structured data suggests that there are many more immunizations in the structured data not present in the text. Thus, the algorithm has specialized utility for augmenting immunization records using text data from individual notes; however, the algorithm's extensibility and generalizability can serve as a framework for future EHR-based research.

During the 2023-2024 and 2024-2025 respiratory virus seasons, two products, a maternal vaccine (Abrysvo, by Pfizer) and an infant monoclonal antibody (nirsevimab), were recommended in the United States to protect infants against severe respiratory syncytial virus (RSV) disease during their first RSV season. We estimated product effectiveness (PE) against RSV-associated emergency department (ED) encounters and hospitalizations among infants in their first RSV season during these seasons.Table 1.Nirsevimab effectiveness against RSV-associated ED encounters and hospitalization among infants in their first RSV season, VISION, 2023-2024 and 2024-2025 RSV seasonsRSV = respiratory syncytial virus; ED = emergency department; IQR = interquartile range; CI = confidence interval; Ref = reference group; PE = product effectiveness; VISION = Virtual SARS-CoV-2, Influenza, and Other respiratory viruses Network*Encounters included those among infants aged <8 months as of October 1 with a diagnosis of RSV-like illness (RLI), excluding infants with evidence of maternal RSV vaccination and infants who received nirsevimab <7 days prior to the index date for the encounter. RLI was defined as ≥1 International Classification of Disease 10th Revision discharge diagnosis code corresponding to one or more of the following: COVID-19 pneumonia, influenza pneumonia, other viral pneumonia, influenza disease, bacterial pneumonia, acute respiratory distress syndrome, asthma exacerbation, respiratory failure, other acute lower respiratory tract infection, sinusitis, acute upper respiratory tract infections, acute respiratory illness signs and symptoms, viral illness not otherwise specified, sepsis, respiratory failure, irritable/fussy infant, respiratory distress of newborn, congenital pneumonia, interstitial emphysema and related conditions, other respiratory conditions originating in the perinatal period, congenital viral diseases, bacterial sepsis of newborn, or other infections specific to the perinatal period.†Encounters with a positive molecular or antigen RSV test 10 days prior to 3 days after the date of the ED encounter or hospital admission were considered RSV-positive.‡PE was calculated as (1 – adjusted odds ratio) x 100%, with adjusted odds ratio estimated using logistic regression, adjusting for age, race and ethnicity, sex, calendar day, and geographic region.Table 2.Maternal RSV vaccine product effectiveness against RSV-associated ED encounters and hospitalization among infants in their first RSV season, VISION, 2023-2024 and 2024-2025 RSV seasonsRSV = respiratory syncytial virus; ED = emergency department; IQR = interquartile range; CI = confidence interval; Ref = reference group; PE = product effectiveness; VISION = Virtual SARS-CoV-2, Influenza, and Other respiratory viruses Network*Encounters included those among infants in their first RSV season with a diagnosis of RSV-like illness (RLI), excluding infants with evidence of nirsevimab receipt and infants born <14 days after maternal RSV vaccine receipt. RLI was defined as ≥1 International Classification of Disease 10th Revision discharge diagnosis code corresponding to one or more of the following: COVID-19 pneumonia, influenza pneumonia, other viral pneumonia, influenza disease, bacterial pneumonia, acute respiratory distress syndrome, asthma exacerbation, respiratory failure, other acute lower respiratory tract infection, sinusitis, acute upper respiratory tract infections, acute respiratory illness signs and symptoms, viral illness not otherwise specified, sepsis, respiratory failure, irritable/fussy infant, respiratory distress of newborn, congenital pneumonia, interstitial emphysema and related conditions, other respiratory conditions originating in the perinatal period, congenital viral diseases, bacterial sepsis of newborn, or other infections specific to the perinatal period.†Days since maternal vaccination included the number of days between maternal RSV vaccine dose receipt and birth and the number of days since birth.‡Encounters with a positive molecular or antigen RSV test 10 days prior to 3 days after the date of the ED encounter or hospital admission were considered RSV-positive.§PE was calculated as (1 – adjusted odds ratio) x 100%, with adjusted odds ratio estimated using logistic regression, adjusting for age, race and ethnicity, sex, calendar day, and geographic region.¶A minimum of 14 days between maternal vaccination and birth was required; infants aged 0-6 days were excluded from this analysis. VISION includes integrated health record data with linkages to state and local immunization information systems from 127 EDs and 107 hospitals. We conducted a test-negative analysis using data from 6 VISION sites, including children with ED encounters and hospitalizations with a diagnosis of RSV-like illness (RLI) during October 2023–March 2024 and October 2024–March 2025 among infants in their first RSV season. PE was estimated for each product, comparing the odds of immunization versus no immunization among RSV-positive cases and RSV-negative controls, adjusting for age, race and ethnicity, sex, calendar day, and geographic region. Of the 8,404 RLI ED encounters and 1,395 RLI hospitalizations among infants in their first RSV season without exposure to maternal RSV vaccine, 2,981 (35%) and 771 (55%) were RSV-positive and 1,448 (17%) and 208 (15%) had evidence of nirsevimab receipt, respectively. Nirsevimab effectiveness was 67% (95% CI: 61-72%) against RSV-associated ED encounters and 92% (95% CI: 87-95%) against RSV-associated hospitalization (Table 1). In 1,508 RLI ED encounters and 421 RLI hospitalizations among infants in their first RSV season without receipt of nirsevimab, 480 (32%) and 222 (53%) were RSV-positive and 261 (17%) and 62 (15%) had evidence of maternal RSV vaccination, respectively. Maternal RSV vaccine PE was 70% (95% CI: 57-79%) against RSV-associated ED encounters and 79% (95% CI: 58-89%) against RSV-associated hospitalization among infants in their first RSV season (Table 2). Both RSV prevention products were effective in preventing RSV-associated ED encounters and hospitalizations among infants in their first RSV season in the United States. It is important to continue monitoring RSV PE during future RSV seasons. Steph Battan-Wraith, PhD, Novavax, Inc.: Grant/Research Support 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 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 Sean M. Chickery, DHSc, Centers for Disease Control and Prevention: Grant/Research Support Gabriela Vazquez-Benitez, PhD, MSc, AbbVie: research funding not related to this study|Sanofi: Grant funding for other research not related to this study S. Bianca Salas, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Pfizer: Grant/Research Support Cassandra Bezi, MPH, Centers for Disease Control and Prevention: 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 William F. Fadel, PhD, Centers for Disease Control and Prevention: Grant/Research 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 Ryan E. Wiegand, PhD, Merck & Co., Inc.: Stocks/Bonds (Public Company)|Sanofi S.A.: Stocks/Bonds (Public Company)

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.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In June 2023, CDC’s Advisory Committee on Immunization Practices recommended adults aged ≥60 years receive one RSV vaccine dose under shared clinical decision making. The recommendation was updated in June 2024 as follows: adults aged ≥75 years and adults aged 60–74 years at increased risk for severe RSV disease are recommended to receive one RSV vaccine dose. Monitoring RSV vaccine uptake informs vaccine effectiveness studies and the impact of updated vaccine recommendations.Figure 1:Biweekly cumulative RSV vaccination coverage, by age group, community-dwelling Medicare Fee-For-Service beneficiaries aged ≥65 Years and enrolled in a Part D plan, United StatesFee-for-Service: enrolled in Medicare Parts A/B (and not Part C) for 365 days prior to reporting period.*6-week reporting lag; data may be incomplete after December 7, 2024.Figure 2:Biweekly cumulative RSV vaccination coverage, by underlying medical condition*, Community-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years and enrolled in Part D plan, United StatesFee-for-Service: enrolled in Medicare Parts A/B for 365 days prior to reporting period.* Conditions included lung disease, hematologic disease, cardiovascular disease, diabetes associated with organ damage, liver disease, obesity, neurologic disease, end stage kidney disease, and immunocompromising conditions. Presence of underlying medical condition (other than immunocompromising conditions) was defined as ≥1 claim in prior 365 days listing ICD-10 diagnosis code corresponding to condition. Presence of immunocompromising condition was defined as ≥2 encounters in prior 183 days with a diagnosis code. Immunocompromising conditions included hematologic malignancy, solid malignancy, transplant, rheumatologic/inflammatory conditions, other intrinsic immune conditions, or HIV. End stage kidney disease was defined as ≥1 claim for dialysis encounter in prior 90 days (excluding acute kidney injury). | †6-week reporting lag; data may be incomplete after December 7, 2024. RSV vaccine uptake was assessed in biweekly periods during June 2023 through January 2025. All Medicare beneficiaries aged ≥65 years, enrolled in Medicare Part D since June 21, 2023, through the last Saturday of a biweekly period, and continuously enrolled in Parts A and B in the 365 days prior to the first day of a biweekly period were included. Vaccination status was determined through Medicare Part D. Beneficiaries who received an RSV vaccine prior to June 21, 2023, were excluded. Vaccine uptake was assessed by age group, nursing home residence, and underlying medical condition (UMC) status.Figure 3:Biweekly cumulative RSV vaccination coverage, by community-dwelling or nursing home-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years and enrolled in Part D plan, United StatesFee-for-Service: enrolled in Medicare Parts A/B for 365 days prior to reporting period.*6-week reporting lag; data may be incomplete after December 7, 2024. | †Regardless of age or underlying medical condition status. An average of 16,176,382 Medicare Fee-For-Service beneficiaries were included in each biweekly period. RSV vaccine uptake sharply increased during June 2023 to January 2024 (19%); uptake was slower during June 2024 to January 2025 (5%) (Figure 1). By January 5–18, 2025, 27% of eligible beneficiaries had received the RSV vaccine. Uptake was higher among those aged ≥75 years (31%) compared to those aged 65-74 years old (24%). RSV vaccine uptake varied by UMC category, with beneficiaries with lung disease having the highest uptake (34%) and beneficiaries with end stage kidney disease having the lowest uptake (18%) (Figure 2). RSV vaccination coverage was consistently lower among nursing home residents compared with community-dwelling beneficiaries (Figure 3). RSV vaccine uptake among Medicare Fee-For-Service beneficiaries aged ≥65 years was modest after updated RSV vaccine recommendations. Differences in RSV vaccine uptake were observed by age group, nursing home residence, and UMCs. Ryan E. Wiegand, PhD, Merck & Co., Inc.: Stocks/Bonds (Public Company)|Sanofi S.A.: Stocks/Bonds (Public Company)

Pregnant women are at higher risk of severe coronavirus disease 2019 (COVID-19) compared with nonpregnant women of reproductive age. During 2023-2024, the Centers for Disease Control and Prevention recommended COVID-19 vaccination for everyone aged 6 months or older, including pregnant women. Using a test-negative design, we assessed the effectiveness of 2023-2024 COVID-19 vaccines against COVID-19-associated emergency department (ED) and urgent care setting encounters among pregnant women aged 18-45 years presenting for care with COVID-19 symptoms from September 2023 to August 2024. Vaccine effectiveness against COVID-19-associated ED and urgent care encounters of one 2023-2024 COVID-19 vaccine dose was 58% (95% CI, 24-77%) among pregnant women and 37% (95% CI, 29-44%) among nonpregnant women of the same age. The 2023-2024 COVID-19 vaccines were associated with a decrease in COVID-19-associated ED and urgent care encounters among pregnant women and nonpregnant women of reproductive age.

Influenza vaccination is particularly important for pregnant women. Using a test-negative, case-control design, we estimated the effectiveness of 2023-2024 seasonal influenza vaccination against influenza-associated emergency department and urgent care (ED/UC) encounters among pregnant and non-pregnant women of reproductive age using data from seven healthcare systems. Eligible encounters were among individuals aged 18-49 years with documented female sex. Vaccine effectiveness (VE) was estimated by comparing the odds of vaccination among influenza-positive cases versus influenza-negative controls, adjusting for site, age, race/ethnicity, calendar time, and gestational age at encounter (in pregnant women). Among pregnant women (N = 3539), VE against influenza-associated ED/UC encounters was 46 % (95 % CI: 36-55) and did not differ by gestational age at vaccination. Among non-pregnant women (N = 57,709), VE against influenza-associated ED/UC encounters was 54 % (95 % CI: 51-56). Influenza vaccination during the 2023-2024 season was similarly effective in both pregnant and non-pregnant women and by timing of vaccine receipt during pregnancy.

Abstract Background In September 2023, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccines for use in persons ≥6 months for prevention of COVID-19, including severe disease. Understanding how well updated COVID-19 vaccines work in the context of high population immunity due to prior infection, vaccination, or both, is important for future vaccine policy decisions, as well as informing patient/provider discussions, and increasing vaccine confidence. Effectiveness of updated (2023-2024) COVID-19 vaccination against laboratory-confirmed COVID-19-associated emergency department/urgent care encounters and hospitalization among immunocompetent adults aged ≥18 years — VISION Network, September 2023–March 2024 Methods VISION, an electronic health record (EHR)-based network including emergency departments/urgent care clinics (ED/UCs) and hospitals including 6 health systems, uses clinician-ordered testing data to estimate vaccine effectiveness (VE) for respiratory viruses. COVID-19 VE was estimated using the test-negative design, comparing the odds of vaccination with a single updated 2023-2024 COVID-19 vaccine dose between patients who tested positive versus those who tested negative for SARS-CoV-2 by molecular assay, adjusting for potential confounders. Effectiveness of updated 2023–2024 (monovalent XBB.1.5) COVID-19 vaccination against laboratory-confirmed COVID-19–associated hospitalization among immunocompromised adults aged ≥18 years — VISION network, September 2023–March 2024 Results A total of 198,345 ED/UC encounters and 59,777 hospitalizations between September 2023-March 2024 among immunocompetent adults ≥18 years with symptoms of COVID-19 were included. VE against COVID-19-associated ED/UC encounters comparing receipt of an updated dose to no receipt of an updated dose was 50% (95% CI: 46-53%) in the 7-59 days and 0 (95% CI: -14 to 12) in the 120-179 days after receipt of an updated dose (Table 1). VE against COVID-19-associated hospitalization was 50% (95% CI: 44-56%) in the 7-59 days and 23 (95% CI: 2-39) in the 120-179 days after receipt of an updated dose (Table 1). A total of 17,417 hospitalizations among immunocompromised adults ≥18 years with symptoms of COVID-19 were included, with a VE of 38% (95% CI: 23-50%) in the 7-59 days and 14 (95% CI: -33 to 44) in the 120-179 days after receipt of an updated dose after an updated dose (Table 2). Conclusion Receipt of an updated COVID-19 vaccine dose provided protection against COVID-19-associated ED/UC encounters and hospitalizations among immunocompetent and immunocompromised adults, although waning was evident. Disclosures Nicola P. Klein, MD, PhD, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Toan Ong, PhD, Patent Title: Systems and Methods For Record Linkage: PCT/US2018/047961 Patent Title: Systems and Methods For Record Linkage|PCORI: Travel support to attend the PCORI Annual meeting in Washington DC, 2023|Regenstrief Institute: Advisor/Consultant|Regenstrief Institute: Travel support to attend the OHIE 23 meeting in Malawi. Brian E. Dixon, PhD, Elsevier: Honoraria

Abstract Background Persons with end stage renal disease (ESRD) on maintenance dialysis are at high risk for severe COVID-19 disease. On September 12, 2023, updated 2023-2024 COVID-19 vaccination was recommended in the United States for all persons aged ≥6 months. Due to the innate immune dysfunction and high prevalence of additional underlying conditions, including immunocompromising conditions (ICs), among individuals with ESRD, there is concern about reduced vaccine effectiveness (VE). Understanding the VE of updated doses among persons with ESRD will inform the need for additional doses in this population. Table 1 Characteristics of Medicare fee-for-service beneficiaries aged ≥18 years with end stage renal disease receiving dialysis1, by presence of additional immunocompromising conditions — United States, September 2023–December 2023 Methods A retrospective cohort study was conducted among Medicare fee-for-service beneficiaries aged ≥18 years with ESRD receiving dialysis using Medicare enrollment and claims records. Follow-up began on September 17, 2023, and continued until the earliest occurrence of a censoring event, COVID-19–associated outcome (medically attended COVID-19 or COVID-19-associated hospitalization), or study end. A marginal structural Cox model was used to estimate VE (calculated as [1 – hazard ratio]*100%), interpreted as the benefit of an updated COVID-19 vaccine dose compared with no updated dose, by presence of additional ICs. Table 2 Vaccine effectiveness1 of updated 2023–2024 (monovalent XBB.1.5) COVID-19 vaccination against medically attended COVID-19 and COVID-19-associated hospitalizations among Medicare fee-for-service beneficiaries aged ≥18 years with end stage renal disease receiving dialysis2, by presence of additional immunocompromising conditions and age group — United States, September 2023–December 2023 Results During September 17 – December 30, 2023, 14,921/112,186 (15%) Medicare beneficiaries aged ≥18 years with ESRD without additional ICs and 5,667/33,957 (17%) beneficiaries aged ≥18 years with ESRD and additional ICs received an updated 2023-2024 COVID-19 vaccine dose (Table 1). Among those with ESRD without additional ICs, VE against medically attended COVID-19 was 47% (95% confidence interval [CI]: 36% - 56%) and against COVID-19-associated hospitalization was 49% (95% CI: 34% - 61%). Among those with ESRD and additional ICs, VE against medically attended COVID-19 was 40% (95% CI: 23% - 53%) and against COVID-19-associated hospitalization was 50% (95% CI: 29% - 64%)(Table 2). Conclusion VE among adults with ESRD was similar to published updated 2023-2024 COVID-19 VE estimates among the general adult population. These data support the recommendation that adults with ESRD get an updated COVID-19 vaccine, especially people 65 years or older and people with ICs, who are eligible for additional doses. Disclosures Ryan E. Wiegand, PhD, Merck & Co, Inc.: Stocks/Bonds (Public Company)|Sanofi ADR: Stocks/Bonds (Public Company) Heng-Ming Sung, MPH, CDC: Author is an employee of Acumen LLC. This study was funded through an inter-agency agreement between CDC and CMS for which Acumen is a contractor. Yue Zhang, MS, CDC: Author is an employee of Acumen LLC. This study was funded through an inter-agency agreement between CDC and CMS for which Acumen is a contractor. Bradley Lufkin, MPA, CDC: Author is an employee of Acumen LLC. This study was funded through an inter-agency agreement between CDC and CMS for which Acumen is a contractor. Yoganand Chillarige, MPA, CDC: Author is an employee of Acumen LLC. This study was funded through an inter-agency agreement between CDC and CMS for which Acumen is a contractor.

COVID-19 vaccination averted approximately 68,000 hospitalizations during the 2023-24 respiratory season. In June 2024, CDC and the Advisory Committee on Immunization Practices (ACIP) recommended that all persons aged ≥6 months receive a 2024-2025 COVID-19 vaccine, which targets Omicron JN.1 and JN.1-derived sublineages. Interim effectiveness of 2024-2025 COVID-19 vaccines was estimated against COVID-19-associated emergency department (ED) or urgent care (UC) visits during September 2024-January 2025 among adults aged ≥18 years in one CDC-funded vaccine effectiveness (VE) network, against COVID-19-associated hospitalization in immunocompetent adults aged ≥65 years in two networks, and against COVID-19-associated hospitalization among adults aged ≥65 years with immunocompromising conditions in one network. Among adults aged ≥18 years, VE against COVID-19-associated ED/UC visits was 33% (95% CI = 28%-38%) during the first 7-119 days after vaccination. Among immunocompetent adults aged ≥65 years from two CDC networks, VE estimates against COVID-19-associated hospitalization were 45% (95% CI = 36%-53%) and 46% (95% CI = 26%-60%) during the first 7-119 days after vaccination. Among adults aged ≥65 years with immunocompromising conditions in one network, VE was 40% (95% CI = 21%-54%) during the first 7-119 days after vaccination. These findings demonstrate that vaccination with a 2024-2025 COVID-19 vaccine dose provides additional protection against COVID-19-associated ED/UC encounters and hospitalizations compared with not receiving a 2024-2025 dose and support current CDC and ACIP recommendations that all persons aged ≥6 months receive a 2024-2025 COVID-19 vaccine dose.

Importance:SARS-CoV-2 continues to evolve, population immunity changes, and COVID-19 vaccine formulas have been updated, necessitating ongoing COVID-19 vaccine effectiveness (VE) monitoring. Objectives:To evaluate the VE of 2023-2024 COVID-19 vaccines against COVID-19-associated emergency department (ED) and urgent care (UC) encounters, hospitalizations, and critical illness, including during XBB- and JN.1-predominant periods. Design, Setting, and Participants:This test-negative design VE case-control study was conducted using data from September 21, 2023, to August 22, 2024, from EDs, UC centers, and hospitals in 6 US health care systems. Eligible adults 18 years or older with COVID-19-like illness and molecular or antigen testing for SARS-CoV-2 were studied. Case patients were those with a positive molecular or antigen test result; control patients were those with a negative molecular test result. Exposure:Receipt of 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination with products approved or authorized for use in the US. Main Outcomes and Measures:Main outcomes were COVID-19-associated ED and UC encounters, hospitalizations, and critical illness (admission to the intensive care unit or in-hospital death). VE was estimated comparing the odds of receipt of the 2023-2024 COVID-19 vaccine with no receipt among case and control patients. Results:Among 345 639 eligible ED and UC encounters in immunocompetent adults 18 years or older with COVID-19-like illness and available test results (median [IQR] age, 53 [34-71] years; 209 087 [60%] female), 37 096 (11%) had a positive SARS-CoV-2 test result. VE against COVID-19-associated ED and UC encounters was 24% (95% CI, 21%-26%) during 7 to 299 days after vaccination. Among 111 931 eligible hospitalizations in immunocompetent adults 18 years or older with COVID-19-like illness and available test results (median [IQR] age, 71 [58-81] years), 10 380 (9%) had a positive SARS-CoV-2 test result. During 7 to 299 days after vaccination, VE was 29% (95% CI, 25%-33%) against COVID-19-associated hospitalization and 48% (95% CI, 40%-55%) against COVID-19-associated critical illness. VE was highest 7 to 59 days after vaccination (VE against ED and UC encounters 49%; 95% CI, 46%-52%; hospitalization, 51%; 95% CI, 46%-56%; critical illness, 68%; 95% CI, 56%-76%) and then waned (VE 180-299 days after vaccination against ED and UC encounters, -7% [95% CI, -13% to -2%]; hospitalization, -4% [95% CI, -14% to 5%]; and critical illness, 16% [95% CI, -6 to 34%]). Conclusions and Relevance:In this case-control study of VE, 2023-2024 COVID-19 vaccines were estimated to provide additional effectiveness against medically attended COVID-19, with the highest and most sustained estimates against critical illness. These results highlight the importance of receiving recommended COVID-19 vaccination for adults 18 years or older.