Interim Estimates of 2024–2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years — VISION and IVY Networks, September 2024–January 2025

Abstract

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.

Introduction

During September 24, 2023–August 11, 2024, approximately 800,000 COVID-19–associated hospitalizations occurred in the United States (1); adults aged ≥65 years accounted for 70% of these hospitalizations (2). During 2024, the SARS-CoV-2 Omicron JN.1 and JN.1-derived lineages predominated and were genomically divergent from the XBB lineages on which the 2023–2024 COVID-19 vaccines were based. On June 27, 2024, CDC’s Advisory Committee on Immunization Practices (ACIP) recommended 2024–2025 COVID-19 vaccination with a Food and Drug Administration (FDA)–authorized or approved vaccine for all persons aged ≥6 months (3). In August 2024, FDA approved monovalent 2024–2025 COVID-19 vaccines by Moderna* and Pfizer-BioNTech^† (based on the SARS-CoV-2 Omicron KP.2 lineage) and authorized a monovalent 2024–2025 COVID-19 vaccine by Novavax^§ (based on the SARS-CoV-2 Omicron JN.1 lineage), for persons aged ≥12 years. For a majority of adults, 1 2024–2025 vaccine dose is recommended, although persons with moderate or severe immunocompromise and adults aged ≥65 years are recommended to receive additional doses, depending on their vaccination history and time since receipt of their most recent dose.^¶

This analysis estimated 2024–2025 COVID-19 vaccine effectiveness (VE) against COVID-19–associated emergency department (ED) or urgent care (UC) visits in one CDC-funded VE network and VE against COVID-19–associated hospitalization in two CDC-funded VE networks during September 2024–January 2025** among adults aged ≥18 years.

Methods

Data Source

Methods for VE analyses in the Virtual SARS-CoV-2, Influenza, and Other respiratory viruses Network (VISION) and Investigating Respiratory Viruses in the Acutely Ill (IVY) network have been reported (4,5). VISION is a multisite, electronic health care records (EHR)–based network including 373 ED/UCs and 241 hospitals in eight states.^†† Eligible patients are those who have received molecular (e.g., real-time reverse transcription–polymerase chain reaction [RT-PCR]) or antigen testing for SARS-CoV-2 during the 10 days preceding or ≤72 hours after an eligible ED/UC encounter or hospital admission.^§§ COVID-19 vaccination history is ascertained from state or jurisdictional registries, EHRs and, in a subset of sites, medical claims data.^¶¶

IVY is a multicenter, inpatient network of 26 hospitals in 20 U.S. states*** and prospectively enrolls adults aged ≥18 years with COVID-19–like illness^††† who receive molecular or antigen testing for SARS-CoV-2 within 10 days of illness onset and within 3 days of hospital admission. Nasal swabs are collected at enrollment for central RT-PCR testing for SARS-CoV-2 at Vanderbilt University Medical Center (Nashville, Tennessee); SARS-CoV-2–positive specimens are sent to the University of Michigan (Ann Arbor, Michigan) for whole genome sequencing to identify SARS-CoV-2 lineages. Demographic and clinical data are collected through EHR review and patient or proxy interview. COVID-19 vaccination history is ascertained from state or jurisdictional registries, EHRs, and plausible self-report based on known location and dates of vaccination.

In both analyses, persons who had received the 2024–2025 COVID-19 vaccine ≥7 days before the encounter index date (VISION) or illness onset date (IVY) were considered vaccinated. Those who had not received the 2024–2025 COVID-19 vaccine (regardless of previous COVID-19 vaccination or infection history) were considered not vaccinated and served as comparators.

Data Analysis

The VISION and IVY networks conducted separate VE analyses using test-negative designs (4,5). In both analyses, adults aged ≥18 years with COVID-19–like illness who 1) had a medical encounter at an ED/UC (VISION only) or 2) were hospitalized (VISION and IVY) at a participating facility were included. Case-patients were those who received a positive SARS-CoV-2 molecular or antigen test result, and control patients were those who received a negative SARS-CoV-2 molecular test result. Participants were excluded if they 1) had received a 2024–2025 COVID-19 vaccine <7 days or ≥120 days before their eligible ED/UC encounter or hospitalization, 2) had received a 2024–2025 COVID-19 vaccine dose <2 months after receiving a previous COVID-19 vaccine dose, or 3) were immunocompetent persons who had received more than 1 2024–2025 COVID-19 vaccine dose. COVID-19 case-patients were also excluded if they were co-infected with influenza or respiratory syncytial virus (RSV) at the time of their COVID-19–like illness encounter. Because of potential confounding from correlated vaccination behaviors, control patients with a positive or indeterminant influenza test result (adults ≥18 years) or a positive RSV test result (adults ≥60 years) were excluded from the primary analysis (6,7). Previous SARS-CoV-2 infections are incompletely documented in medical records; therefore, patients were included regardless of prior SARS-CoV-2 infections.

Odds ratios (OR) and 95% CIs were estimated using multivariable logistic regression, comparing persons who received a 2024–2025 COVID-19 vaccine dose with those who did not among case- and control patients, regardless of previous COVID-19 vaccination. VE models were adjusted a priori for age, sex, race and ethnicity, calendar time, and geographic region.^§§§ VE was calculated as (1 − adjusted OR) x 100% during the first 7–119 days since receipt of a 2024–2025 COVID-19 vaccine dose and separately during the first 7–59 days and 60–119 days since receipt of a dose. For ED/UC encounters, VE was estimated for persons aged ≥18 years, 18–64 years, and ≥65 years (Supplementary Table 1, https://stacks.cdc.gov/view/cdc/176586). Statistical power to estimate VE against hospitalization was limited in adults aged 18–64 years; therefore, VE against hospitalization was only estimated for adults aged ≥65 years in both networks. In the IVY network, VE against hospitalization was estimated in immunocompetent adults due to limited statistical power to assess VE for immunocompromised adults; in VISION, VE was estimated for all adults in the ED/UC setting and separately for adults with and without immunocompromising conditions in the hospital setting.^¶¶¶ The distribution of case- and control patients aged 5–17 years was explored in VISION; however, statistical power was limited in both the ED/UC and hospital settings, so frequencies are described without VE estimation (Supplementary Table 2; https://stacks.cdc.gov/view/cdc/176592).

Analyses were conducted using R software (version 4.3.2; R Foundation) for the VISION analysis and R software (version 4.4.0; R Foundation) for the IVY network analysis. This activity was reviewed by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy.****

Results

2024–2025 COVID-19 VE Against COVID-19–associated ED/UC Visits, VISION

Among adults aged ≥18 years in VISION, 137,543 ED/UC encounters met criteria for inclusion in the analyses, including 10,459 (8%) case-patients and 127,084 (92%) control patients (Table 1). Effectiveness of a 2024–2025 COVID-19 vaccination against a COVID-19–associated ED/UC visit was 33% (95% CI = 28%–38%) during the first 7–119 days after vaccination, 36% (95% CI = 29%–42%) during the first 7–59 days after vaccination, and 30% (95% CI = 22%–37%) during the 60–119 days after vaccination (Table 2).

2024–2025 COVID-19 VE Against COVID-19–associated Hospitalization, VISION and IVY Networks Among Older Adults

Among adults aged ≥65 years without immunocompromising conditions in VISION, 26,219 hospitalizations met criteria for inclusion in analyses, including 2,248 (9%) case-patients and 23,971 (91%) control patients. VE of a 2024–2025 COVID-19 vaccine dose against COVID-19–associated hospitalization was 45% (95% CI = 36%–53%) a median interval of 53 days since receipt of a 2024–2025 COVID-19 vaccine dose (Table 3). Among adults aged ≥65 years with immunocompromising conditions in VISION, 8,192 hospitalizations met criteria for inclusion in analyses, including 598 (7%) case-patients and 7,594 (93%) control patients. VE was 40% (95% CI = 21%–54%), a median interval of 53 days after receipt of a 2024–2025 COVID-19 vaccination. Among adults aged ≥65 years without immunocompromising conditions in the IVY network, 1,929 met inclusion criteria, including 683 (35%) case-patients and 1,246 (65%) control patients. VE against COVID-19–associated hospitalization was 46% (95% CI = 26%–60%), a median of 60 days after receipt of a 2024–2025 COVID-19 vaccine dose.

Whole Genome Sequencing of SARS-CoV-2 Specimens, IVY Network

Among adults aged ≥18 years in the IVY network, 653 SARS-CoV-2–positive specimens collected during September 1, 2024–December 31, 2024 were successfully sequenced; 55 (8.4%) had JN.1-like spike proteins, 92 (14.1%) had KP.2-like proteins, 340 (52.1%) had KP.3-like proteins, 126 (19.3%) had XEC-like proteins, and 40 (6.1%) had other spike proteins.^†††† Similarly, among 6,491 SARS-CoV-2–positive specimens collected during the same period and sequenced by CDC as part of national genomic surveillance,^§§§§ 928 (14.3%) had JN.1-like spike proteins, 982 (15.1%) had KP.2-like proteins, 3,430 (52.8%) had KP.3-like proteins, 894 (13.8%) XEC-like proteins, and 257 (4.0%) had other spike proteins.

Discussion

During September 2024–January 2025, 2024–2025 COVID-19 vaccination provided additional protection against COVID-19–associated ED/UC encounters and hospitalizations among adults with and without immunocompromising conditions, compared with not receiving a 2024–2025 COVID-19 vaccine dose. These results support current CDC recommendations for 2024–2025 COVID-19 vaccination, irrespective of previous COVID-19 vaccination and infection history, and represent the added benefit of 2024–2025 COVID-19 vaccination above existing protection from previous vaccination or infection (3).

During the analytic period, the primary circulating SARS-CoV-2 lineages were descendants of the Omicron JN.1 lineage, including KP.2, KP.3, and XEC.^¶¶¶¶ XEC is closely related to the KP.2 and JN.1 strains in the 2024–2025 COVID-19 vaccines, which might account for the sustained protection from COVID-19 vaccination observed during the analysis period, despite the emergence and increasing prevalence of XEC. Starting in January 2025, prevalence of LP.8.1 (a JN.1 and KP.1.1 descendent) began to increase, accounting for 31% of sequences in CDC’s national genomic surveillance as of February 15, 2025. The pace and frequency with which new SARS-CoV-2 lineages have become predominant underscores the need for ongoing monitoring of COVID-19 VE and genomic surveillance.

COVID-19–associated hospitalization rates during the time frame of this analysis were relatively low compared with those during previous years, precluding estimation of VE against critical illness (i.e., intensive care unit admission, invasive mechanical ventilation, or death); VE against these outcomes has historically been higher and more sustained than that against less severe outcomes (4,5,8). Because of both lower hospitalization rates and lower vaccination rates,***** VE could not be estimated for children and adolescents aged 5–17 years for either outcome or for adults aged 18–64 years against hospitalization. Analyses from previous years have indicated that COVID-19 vaccines provide similar protection across age groups. For the 2023–2024 COVID-19 vaccines, VE against ED/UC encounters during the first 60–179 days after vaccination was 24% (95% CI = -31% to 56%) for children aged 9 months–4 years, 50% (95% CI = 22%–68%) for children and adolescents aged 5 years–17 years, 24% (95% CI = 17%–31%) for adults aged 18–64 years, and 25% (95% CI = 20%–30%) for adults aged ≥65 years.^{†††††}

Previous SARS-CoV-2 infection contributes protection against future disease, although protection wanes over time (9). An increase in SARS-CoV-2 circulation in the United States during late summer 2024, just before the 2024–2025 COVID-19 vaccines were approved and authorized, might have resulted in higher population-level immunity against JN.1-lineage strains, which could have resulted in lower measured VE than would have been detected in a population with less recent infection. Analyses did not account for previous SARS-CoV-2 infection or previous COVID-19 vaccination (e.g., original monovalent, bivalent, or 2023–2024 doses). VE should therefore be interpreted as the added benefit of 2024–2025 COVID-19 vaccination in a population with high levels of infection-induced immunity, vaccine-induced immunity, or both.

Limitations

The findings in this report are subject to at least four limitations. First, although case-patients were those who met a COVID-19–like illness definition and had a positive SARS-CoV-2 test result, they might have visited ED/UCs or been hospitalized for reasons other than COVID-19, which might have lowered VE estimates. Second, misclassification of vaccination status was possible, which would likely result in underestimation of VE if the misclassification was nondifferential. Third, lack of statistical power prevented estimation of VE in some strata, including younger age groups. Finally, although analyses were adjusted for some relevant confounders, residual confounding from other factors, such as behavioral modifications to prevent SARS-CoV-2 exposure and outpatient antiviral treatment for COVID-19, might remain.

Implications for Public Health Practice

In this analysis, receipt of a 2024–2025 COVID-19 vaccine dose provided additional protection against COVID-19–associated ED/UC visits and hospitalization among adults with and without immunocompromise. These results support CDC and ACIP recommendations for 2024–2025 COVID-19 vaccination (3). CDC continues to monitor VE of 2024–2025 COVID-19 vaccines.

CDC COVID-19 Vaccine Effectiveness Collaborators

Joshua Acidera, University of Washington/Harborview; Laura Aguilar Marquez, University of Colorado; Omobosola Akinsete, HealthPartners Institute; Harith Ali, Johns Hopkins University; Erika Alor, University of Colorado; Ike Appleton, University of Iowa; Julie Arndorfer, Intermountain Health; Olivia Arter, Washington University School of Medicine; Sarah W. Ball, Westat, Inc; Jaskiran Bansal, Henry Ford Health; Anna Barrow, University of Colorado; Leonard Basobas, Stanford University; Adrienne Baughman, Vanderbilt University Medical Center; Paul W. Blair, Vanderbilt University Medical Center; Lawrence Block, Kaiser Permanente Northern California; Bryce Bosworth, University of Utah; Noah Brazer, Yale School of Medicine; Genesis Briceno, Oregon Health & Science University; Daniel Bride, Intermountain Health; Samuel M. Brown, Stanford University; Sydney Buehrig, Baylor Scott & White Health, Baylor University Medical Center, Dallas; Ashley Bychkowski, Baylor Scott & White Health, Baylor University Medical Center, Dallas; Sukantha Chandresakaran, University of California Los Angeles; Steven Y. Chang, University of California Los Angeles; Catia Chavez, University of Colorado School of Medicine; Dylan Clark, University of Washington/Harborview; Sydney A. Cornelison, Vanderbilt University Medical Center; Jonathan M. Davis, Westat, Inc.; Brian E. Dixon, Regenstrief Institute Center for Biomedical Informatics and Richard M Fairbanks School of Public Health; Thomas J. Duszynski, Regenstrief Institute Center for Biomedical Informatics and Richard M Fairbanks School of Public Health; Inih Essien, HealthPartners Institute; Yvette Evans, University of Colorado; William F. Fadel, Regenstrief Institute Center for Biomedical Informatics and Richard M Fairbanks School of Public Health; Cathy Fairfield, University of Iowa; Courtney Feitsam, University of Iowa; Samantha Ferguson, Stanford University; Tammy Fisher, Baylor Scott & White Health, Baylor University Medical Center, Dallas; Omai Garner, University of California Los Angeles; Sheila Gasparek, Baylor Scott & White Health, Baylor University Medical Center, Dallas; Heath Gibbs, University of Iowa; Daniela Gonzalez, Baylor Scott & White Health, Baylor University Medical Center, Dallas; Alexandra June Gordon, Stanford University; Anirudh Goyal, Yale School of Medicine; Carlos G. Grijalva, Vanderbilt University Medical Center; Sydney Guthrie-Baker, Stanford University; Jacob Hampton, University of Iowa; John Hansen, Kaiser Permanente Northern California; Ebaad Haq, Oregon Health & Science University; Adrian Hernandez-Frausto, Oregon Health & Science University; Kinsley Hubel, Oregon Health & Science University; Mariana Hurutado-Rodriguez, Baylor Scott & White Health, Baylor University Medical Center, Dallas; Cameron Hypes, University of Arizona; Karen B. Jacobson, Kaiser Permanente Northern California; Milad Karami Jouzestani, Oregon Health & Science University; Sindhuja Koneru, Henry Ford Health; Padma Koppolu, Kaiser Permanente Center for Health Research; Olivia Krol, Oregon Health & Science University; Lily Lau, Stanford University; Jenna Lumpkin, Stanford University; Karen Lutrick, University of Arizona; Cara T. Lwin, Vanderbilt University Medical Center; Kevin Ma, CDC; Kimberly Manchester, Yale School of Medicine; Denisse Mariscal, Baylor Scott & White Health, Baylor University Medical Center, Dallas; Amanda Martinez, University of Colorado; David Mayer, University of Colorado School of Medicine; Rylie McBride, University of Utah; David McDonald, Washington University School of Medicine; Maile McKeown, University of Washington/Harborview; Sachina Mensah, Washington University School of Medicine; Nicholas Mohr, University of Iowa; Paul Nassar, University of Iowa; Caroline O’Neil, Washington University School of Medicine; Josh Van Otterloo, Intermountain Health; Elianora Ovchiyan, Washington University School of Medicine; Bijal Parikh, Washington University School of Medicine; Jose Pena, Oregon Health & Science University; Cynthia Perez, Stanford University; Gabriela Perez, Baylor Scott & White Health, Baylor University Medical Center, Dallas; Vanessa Pitre, Stanford University; Edvinas Pocius, Oregon Health & Science University; Jacob Rademacher, University of Colorado; Mayur Ramesh, Henry Ford Health; Caitlin Ray, CDC and Goldbelt Professional Services LLC; Carolina Rivas, University of Miami; Safa Saeed, Johns Hopkins University; Akshay Saluja, Washington University School of Medicine; Elizabeth Salvagio Campbell, University of Arizona; Carleigh Samuels, Washington University School of Medicine; Maria Santana-Garces, Henry Ford Health; Tanisha Shack, Henry Ford Health; Samantha Simon, University of Colorado; Ine Sohn, Vanderbilt University Medical Center; Vasisht Srinivasan, University of Washington/Harborview; Hannah Strait, Wake Forest University; Amy Sullivan, University of Colorado; H. Keipp Talbot, Vanderbilt University Medical Center; Grace Kyin-ye Tam, Stanford University; Shruti Tirumala, Henry Ford Health; Cody Tran, University of California Los Angeles; Emily Tribbett, Oregon Health & Science University; Alyssa Valencia, Washington University School of Medicine; Ivan Valesquez, Yale School of Medicine; Lucy Vogt, Washington University School of Medicine; Kim Vu, Washington University School of Medicine; Francesca Yerbic, Washington University School of Medicine; Arda Yigitkanli, Yale School of Medicine; Anne Zepeski, University of Iowa