2024-2025 COVID-19 Vaccines Provided Moderate Protection Against JN.1 Variants

COVID-19 vaccination showed effectiveness in reducing hospitalizations and severe disease outcomes associated with the SARS-CoV-2 JN.1 lineage, according to a recent study published in JAMA Network Open.¹

COVID-19 is still a public threat and health concern. Between 2024 and 2025, an estimated 380,000 to 540,000 patients were hospitalized and between 44,000 and 63,000 deaths occurred due to the virus in the US. The uptick in COVID-19 cases was primarily due to the newer variant of the virus, shifting from XBB to JN.1 lineages. In response to the shift, in 2024, the FDA approved updated vaccines from Moderna and Pfizer based on the KP.2 lineage and an updated Novavax vaccine based on the JN.1 lineage. The SARS-CoV-2 JN.1 lineage descendants continued to evolve throughout the 2024-2025 season, thus encouraging researchers to reevaluate the efficacy of the COVID-19 vaccine. In the current study, researchers estimated the vaccine effectiveness of the SARS-CoV-2 JN.1 lineage descendants and their impact on related hospitalizations and severe in-hospital outcomes.

The case-controlled study prospectively enrolled patients 18 years and older who were admitted to hospitals in the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network multicenter surveillance consortium between September 1, 2024, and April 30, 2025. There were 8493 patients enrolled in the study; 1888 had COVID-19 and the remaining 6605 were control patients. Overall, the median age of patients was 66 years; of them, 51.1% were female and 48.9% were male.

Patient demographics showed that 1061 (12.5%) identified as Hispanic or Latino ethnicity, 1905 (22.4%) as non-Hispanic Black, 4883 (57.5%) as non-Hispanic White, 434 (5.1%) as non-Hispanic other race, and 210 (2.5%) as unknown race and ethnicity. COVID-19 case patients were younger compared with control patients (median [IQR] age, 65 years [53-75] vs 71 [59-80] years; P < .001) and had a lower Charlson Comorbidity Index (median [IQR], 4 [2-6] vs 5 [3-7]; P < .001).

Of the 1888 case patients, only 216 (11.4%) received a 2024-2025 COVID-19 vaccine compared with 1224 (18.5%) of 6605 control patients. Among the 6131 immunocompetent adults, the overall effectiveness of the 2024-2025 COVID-19 vaccines against COVID-19–associated hospitalization was 40% (95% CI, 27%-51%), with a median (IQR) time since dose receipt of 80 days (43-137) among case patients and 108 days (66-151) among control patients.

The vaccine effectiveness was 34% (95% CI, 14%-49%) at 7 to 89 days after vaccination and 52% (95% CI, 34%-65%) at 90 to 179 days after vaccination. In immunocompetent adults 65 years or older, vaccine effectiveness was 45% (95% CI, 31%-56%) overall, 44% (95% CI, 25%-59%) at 7 to 89 days after vaccination, and 51% (95% CI, 31%-66%) at 90 to 179 days after vaccination.

Prior studies have shown that vaccination against COVID-19 reduced the risk of long COVID by 36% in adolescents aged 12 to 17 years.²

This analysis was limited by declining hospitalization numbers, which hindered long-term effectiveness estimates, and the study did not account for prior infections or vaccinations that could affect vaccine effectiveness. Additionally, incomplete sequencing, potential lack of national generalizability, and residual confounding may limit the findings.

“During a season without major antigenic changes to circulating SARS-CoV-2 viruses, we found sustained protection from COVID-19 vaccines through at least 90 to 179 days after vaccination,” the study authors concluded. “Monitoring COVID-19 [vaccine effectiveness], including stratifying by SARS-CoV-2 lineage and spike protein mutations, remains important to guide COVID-19 vaccine composition and recommendations.”

References

1. Ma KC, Webber A, Lauring AS, et al. Estimated effectiveness of 2024-2025 COVID-19 vaccination against severe COVID-19. JAMA Netw Open. 2026;9(2):e2557415. doi:10.1001/jamanetworkopen.2025.57415

2. McCormick B. COVID-19 vaccination linked to lower risk of long COVID in adolescents. AJMC^®. November 3, 2025. Accessed February 18, 2026. https://www.ajmc.com/view/covid-19-vaccination-linked-to-lower-risk-of-long-covid-in-adolescents