Estimated 2023-2024 COVID-19 Vaccine Effectiveness in Adults

Link-Gelles R, Rowley EAK, Irving SA, et al.. JAMA Netw Open - Published Online: June 25, 2025;8;(6):e2517402. doi:10.1001/jamanetworkopen.2025.17402

Key Points

Question  What is the vaccine effectiveness (VE) of 2023-2024 COVID-19 vaccines against medically attended COVID-19, including during Omicron XBB and JN.1 sublineage predominance?

Findings  This test-negative case-control study included 345 955 emergency department and urgent care encounters and 111 931 hospitalizations among adults with COVID-19–like illness. During 7 to 299 days after 2023-2024 COVID-19 vaccination, VE was 29% against COVID-19–associated emergency department and urgent care encounters, 30% against COVID-19–associated hospitalization, and 48% against COVID-19–associated critical illness, with VE being the highest 7 to 59 days after vaccination and waning against all outcomes.

Meaning  In this study, the 2023-2024 COVID-19 vaccines were associated with fewer cases of medically attended COVID-19, with more robust outcomes for critical illness; however, VE waned over time, supporting recommendations for all adults to receive 2024 to 2025 COVID-19 vaccination.

Abstract

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.

Vaccine Effectiveness Among Adults 18 Years or Older Without
Documented Immunocompromise, September 2023- August 2024

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.

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