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JAMA Netw Open . Interim Estimated Effectiveness of 2025-2026 COVID-19 Vaccines in Adults Using a Test-Negative Design

tetano

Editor, Senior Moderator
JAMA Netw Open


. 2026 Jun 1;9(6):e2625152.
doi: 10.1001/jamanetworkopen.2026.25152.
Interim Estimated Effectiveness of 2025-2026 COVID-19 Vaccines in Adults Using a Test-Negative Design

Ryan E Wiegand[SUP] 1 [/SUP], Sean Chickery[SUP] 2 [/SUP], Duck-Hye Yang[SUP] 2 [/SUP], Sarah W Ball[SUP] 2 [/SUP], Malini B DeSilva[SUP] 3 [/SUP], Kristin Dascomb[SUP] 4 [/SUP], Stephanie A Irving[SUP] 5 [/SUP], Karthik Natarajan[SUP] 6 [/SUP], Nicola P Klein[SUP] 7 [/SUP], Shaun J Grannis[SUP] 8 9 [/SUP], Toan C Ong[SUP] 10 [/SUP], Elizabeth A K Rowley[SUP] 2 [/SUP], Adam Yates[SUP] 2 [/SUP], Yan Zhuang[SUP] 2 [/SUP], Sarah Wilson[SUP] 2 [/SUP], Charlene E McEvoy[SUP] 3 [/SUP], Inih J Essien[SUP] 3 [/SUP], Omobosola O Akinsete[SUP] 3 [/SUP], Allison L Naleway[SUP] 5 [/SUP], Padma Koppolu[SUP] 5 [/SUP], Ousseny Zerbo[SUP] 7 [/SUP], John R Hansen[SUP] 7 [/SUP], Karen B Jacobson[SUP] 7 [/SUP], Lawrence Block[SUP] 7 [/SUP], Brian E Dixon[SUP] 8 11 [/SUP], Thomas Duszynski[SUP] 8 12 [/SUP], Colin Rogerson[SUP] 8 13 [/SUP], Michelle A Barron[SUP] 10 [/SUP], Catia Chavez[SUP] 10 [/SUP], Josephine Mak[SUP] 1 [/SUP], Allison Avrich Ciesla[SUP] 1 14 [/SUP], Monica Godfrey[SUP] 1 [/SUP], Amber Kautz[SUP] 1 15 [/SUP], Morgan Najdowski[SUP] 1 14 [/SUP], Ruth Link-Gelles[SUP] 1 16 [/SUP], Jennifer DeCuir[SUP] 1 [/SUP], Amanda B Payne[SUP] 1 [/SUP]


Affiliations
Free article Abstract

Importance: The 2025-2026 COVID-19 vaccine, targeting JN.1 and JN.1-derived sublineages, became available in the US in September 2025.
Objective: To assess the estimated interim effectiveness of 2025-2026 COVID-19 vaccines against medically attended COVID-19 among immunocompetent adults aged 18 years or older in the US.
Design, setting, and participants: This case-control study used a test-negative design to investigate patient encounters captured in the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network, an electronic medical record-based network of health care systems (253 emergency departments/urgent cares [ED/UCs] and 179 hospitals in 7 states) from September 3, 2025, to December 31, 2025. Patient encounters with COVID-19-like illness and a molecular or antigen SARS-CoV-2 test 10 days before to 3 days after the encounter date were included.
Exposure: 2025-2026 COVID-19 vaccination regardless of prior COVID-19 vaccination.
Main outcomes and measures: The main outcomes were COVID-19-associated ED/UC encounters and COVID-19-associated hospitalizations. Cases were defined as encounters with a positive molecular or antigen SARS-CoV-2 test and controls as encounters with a negative molecular SARS-CoV-2 test. The odds of 2025-2026 COVID-19 vaccination among cases and controls, adjusting for confounders, were compared and used to estimate vaccine effectiveness (VE) as (1 - adjusted odds ratio) × 100%.
Results: In 85 725 ED/UC encounters among adults aged 18 years and older (51 841 [60%] aged 18-64 years; 51 775 female [60%]), 206 of 3941 cases (5%) and 9453 of 81 784 controls (12%) received a 2025-2026 COVID-19 vaccination. Estimated VE against COVID-19-associated ED/UC encounters was 50% (95% CI, 42%-57%; median [IQR] time since 2025-2026 COVID-19 vaccine dose receipt, 47 [27-69] days). In 26 073 hospitalizations with a COVID-19-like illness (17 530 [67%] aged ≥65 years; 13 985 female [54%]), 60 of 1022 cases (6%) received a 2025-2026 COVID-19 vaccination compared with 3080 of 25 051 controls (12%). Estimated VE against COVID-19-associated hospitalization was 55% (95% CI, 41%-66%; median [IQR] time since 2025-2026 COVID-19 vaccine dose receipt, 46 [26-68] days). Among patients aged 65 years or older, estimated VE against ED/UC encounters was 48% (95% CI, 37%-56%; median [IQR] time since dose receipt, 48 [27-69] days; 33 884 encounters) and against hospitalization was 53% (95% CI, 37%-65%; median [IQR] time since dose receipt, 46 [26-69] days; 17 530 hospitalizations).
Conclusions and relevance: In this study, receipt of 2025-2026 COVID-19 vaccination was associated with additional protection beyond existing immunity in adults against medically attended COVID-19, including ED/UC encounters and hospitalizations, compared with no receipt of a 2025-2026 vaccine dose. These findings suggest that adults can reduce their likelihood of severe COVID-19-associated outcomes by obtaining a 2025-2026 COVID-19 vaccination.


 
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