CDC-Led Study Affirms Robust Effectiveness of 2023-2024 COVID-19 Vaccines in Reducing Illness Severity, Mortality

The 2023-2024 COVID-19 vaccines provided significant additional protection—on top of innate immunity and prior vaccination—towards medically attained COVID-19, with heightened effectiveness in preventing severe illness, including during the predominance of Omicron XBB and JN.1 variants, according to results from a large, multisite electronic health record-based collaboration between the CDC and health care systems.^1,2

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Importance of Timely Assessments of COVID-19 Vaccination

Spanning more than 345,000 emergency department (ED)/urgent care (UC) encounters and over 111,000 hospitalizations in 230 hospitals and 362 EDs and UCs across the United States, the study found that, despite strong vaccine effectiveness (VE) against critical illness in a variety of subgroups—including immunocompromised individuals—protection waned over time for mild or moderate illness. This observation emphasizes the importance of receiving routine, updated COVID-19 vaccinations that protect against currently circulating variants.^1,2

Since COVID-19 vaccines were first introduced, manufacturers have produced yearly updated vaccines against new strains of the virus. Accordingly, the CDC, through the Advisory Committee on Immunization Practices (ACIP), recommends the COVID-19 vaccine for use in specific age groups. The 2023-2024 COVID-19 vaccines, designed to protect against the XBB.1.5 Omicron variant, were recommended by the ACIP and CDC for use in those ages 6 months and older.^1,3

In the years since that respiratory season, new vaccines that included JN.1 and KP.2 were developed for the 2024-2025 season, and subsequent vaccines are in development by manufacturers for the 2025-2026 respiratory season. What remains clear is that SARS-CoV-2 continues to evolve at a rapid pace, necessitating timely assessments of VE among the population. Critically, VE estimates are interpreted as additional benefit provided by vaccination above existing protection from prior infection and/or vaccination.^1,2

Health Records Indicate Broad, Strong Added Protection With COVID-19 Vaccines

Through the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (VISION), which is a collaboration between the CDC and numerous health systems in 6 states, the investigators examined electronic health record data, as well as vaccination and laboratory records, for individuals ages 18 years and older who did and did not receive one of the 2023-2024 monovalent XBB.1.5 COVID-19 vaccines. The study period was from September 21, 2023, to August 22, 2024.¹

A total of 345,639 eligible ED and UC encounters were included in the analysis, of which 37,096 had a positive SARS-CoV-2 test result. Among these, 5929 (16%) received the vaccine, compared with 59,977 vaccinated control encounters with a negative test result. Against COVID-19-associated ED and UC encounters, VE was 24% (95% CI, 21%–26%) in the 7 to 299 days after vaccination. In the 7 to 59 days following vaccination, VE was 49% (95% CI, 45%–52%), though it decreased to –7% (95% CI, –13% to –2%) in the 180 to 299 days following vaccination. VE remained significant during XBB predominance (50% [95% CI, 46%–54%).¹

Regarding hospitalizations, VE against COVID-19-associated hospitalizations was 29% (95% CI, 25%–33%) during 7 to 299 days post-vaccination. In the 7 to 59 days after vaccination, VE was 51% (95% CI, 46%–56%) and decreased to –4% (95% CI, –14% to 5%). Contrasting with the ED and UC setting, which found similar effectiveness across age groups, VE estimates against hospitalization were generally higher among those ages 65 years or older versus those ages 18 to 64 years, according to the investigators. VE was especially robust during XBB predominance.¹

As the investigators noted in their discussion, waning protection was evident in the analysis. They discussed how higher rates of prior infection with SARS-CoV-2 in the comparator population (those without 2023-2024 COVID-19 vaccines) early in the study period may have, in turn, reduced the measured VE due to a greater amount of time since the last dose.^1,2

They also explained how the results from this analysis do not control for prior infection, lending credence to the hypothesis that measured VE in the analysis is a likely underestimate of the true protection elicited from vaccination. Furthermore, the results underscore the importance of patients staying up to date on CDC-recommended COVID-19 vaccination, especially for adults 65 years and older, for whom vaccination is especially efficacious.^1,2

REFERENCES

1. Link-Gelles R, Rowley EAK, Irving SA, et al. Estimated 2023-2024 COVID-19 vaccine effectiveness in adults. JAMA Netw Open. 2025;8(6):e2517402. doi:10.1001/jamanetworkopen.2025.17402

2. Regenstrief Institute. COVID vaccine reduces severity of illness, death for adults, especially among at-risk populations. EurekAlert! News Release. Released June 25, 2025. Accessed July 16, 2025. https://www.eurekalert.org/news-releases/1088755

3. Gallagher A. CDC’s ACIP votes in favor of universal recommendation for 2023-2024 monovalent COVID-19 vaccines. Pharmacy Times. Published September 13, 2025. Accessed July 16, 2025. https://www.pharmacytimes.com/view/cdc-s-acip-votes-in-favor-of-universal-recommendation-for-2023-2024-monovalent-covid-19-vaccines