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J Infect Dis
. 2026 Mar 2:jiag137.
doi: 10.1093/infdis/jiag137. Online ahead of print.
2024-2025 COVID-19 mRNA Vaccine Effectiveness against Severe Disease
Iromi Jayawardena 1 2 , Natalie E Dean 3 , Brian Witrick 1 2 , Alain H Litwin 4 5 6 , Lior Rennert 1 2
Affiliations
Background: This study evaluated the effectiveness of the 2024-2025 coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine against COVID-19 emergency department (ED) and hospital admissions.
Methods: We used electronic health records in a large South Carolina health system to emulate a target trial comparing individuals aged 18 and older who received versus did not receive the 2024-2025 COVID-19 mRNA vaccine. Individuals who received the vaccine during the study period (9/1/2024-3/15/2025) were risk-set matched with unvaccinated individuals based on demographic and clinical covariates using propensity score matching (1:2). The primary outcomes were time to ED or hospitalization admission between September 01, 2024, to April 16, 2025, analyzed with Cox proportional hazards models.
Results: The participation criteria resulted in 157,988 individuals, of whom 10,041 (6.4%) received the updated 2024-2025 COVID-19 vaccine. The final matched sample included 30,080 individuals, with 10,029 receiving the vaccine. mRNA vaccine protection was 41.3% (95% CI: 17.2-58.4) against ED or more severe care and 46.1% (95% CI: 13.6-66.3) against hospitalization.
Conclusion: These findings demonstrate that the 2024-2025 mRNA COVID-19 vaccine had moderate protection against hospitalization and ED or more severe care, even in a southern US state with a significant rural population and high levels of prior exposure through infection and/or previous vaccination. Given the low vaccine uptake in this population, our results underscore the need for sustained public health efforts to increase vaccination coverage and address the challenges posed by emerging variants, particularly among older adults and those with medical comorbidities.
Keywords: COVID-19; Target trial emulation; Vaccine effectiveness; mRNA vaccine.
. 2026 Mar 2:jiag137.
doi: 10.1093/infdis/jiag137. Online ahead of print.
2024-2025 COVID-19 mRNA Vaccine Effectiveness against Severe Disease
Iromi Jayawardena 1 2 , Natalie E Dean 3 , Brian Witrick 1 2 , Alain H Litwin 4 5 6 , Lior Rennert 1 2
Affiliations
- PMID: 41766610
- DOI: 10.1093/infdis/jiag137
Background: This study evaluated the effectiveness of the 2024-2025 coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine against COVID-19 emergency department (ED) and hospital admissions.
Methods: We used electronic health records in a large South Carolina health system to emulate a target trial comparing individuals aged 18 and older who received versus did not receive the 2024-2025 COVID-19 mRNA vaccine. Individuals who received the vaccine during the study period (9/1/2024-3/15/2025) were risk-set matched with unvaccinated individuals based on demographic and clinical covariates using propensity score matching (1:2). The primary outcomes were time to ED or hospitalization admission between September 01, 2024, to April 16, 2025, analyzed with Cox proportional hazards models.
Results: The participation criteria resulted in 157,988 individuals, of whom 10,041 (6.4%) received the updated 2024-2025 COVID-19 vaccine. The final matched sample included 30,080 individuals, with 10,029 receiving the vaccine. mRNA vaccine protection was 41.3% (95% CI: 17.2-58.4) against ED or more severe care and 46.1% (95% CI: 13.6-66.3) against hospitalization.
Conclusion: These findings demonstrate that the 2024-2025 mRNA COVID-19 vaccine had moderate protection against hospitalization and ED or more severe care, even in a southern US state with a significant rural population and high levels of prior exposure through infection and/or previous vaccination. Given the low vaccine uptake in this population, our results underscore the need for sustained public health efforts to increase vaccination coverage and address the challenges posed by emerging variants, particularly among older adults and those with medical comorbidities.
Keywords: COVID-19; Target trial emulation; Vaccine effectiveness; mRNA vaccine.