The study found that influenza vaccine effectiveness in preventing influenza did not meaningfully differ according to the time of day the vaccine was administered. Although the within-person study design helped reduce confounding, residual confounding cannot be completely excluded, representing an important study limitation.
Influenza remains a major public health concern, contributing to considerable illness and deaths each year. While previous research has suggested that factors such as the month of vaccination and the body's circadian rhythm may influence immune responses, evidence linking vaccination timing during the day with real-world clinical outcomes has been limited. To address this gap, researchers led by Karen K. Wong, MD, MPH, MIDS, and Anupam B. Jena evaluated whether receiving an influenza vaccine in the morning or later in the day affected the risk of developing influenza.
The researchers analyzed deidentified electronic health record data from the Cosmos database, comprising more than 300 healthcare organizations using Epic Systems. The study included adults aged 18 years or older who received a single influenza vaccine between 7 a.m. and 5 p.m. during the 2023-2024, 2024-2025, or 2025-2026 influenza seasons.
The primary outcome was a healthcare-confirmed influenza diagnosis occurring at least two weeks after vaccination within the same season, while influenza-related hospitalization was assessed as a secondary outcome. To minimize confounding, the researchers used a within-person analysis comparing individuals vaccinated at different times across multiple seasons.
Overall, 15.9 million adults received more than 23 million influenza vaccinations. The median participant age was 58 years, with women accounting for nearly 60% of the cohort. Vaccinations were most frequently administered between 8 a.m. and 10 a.m., with a second peak between noon and 2 p.m. Among participants who later developed influenza, the median time from vaccination to diagnosis was 98 days.
Key Findings:
- The within-person analysis included more than 5.4 million adults who received influenza vaccinations in at least two different influenza seasons.
- A statistical association was observed between the hour of vaccination and the likelihood of a subsequent influenza diagnosis.
- However, the differences across vaccination times were very small and not clinically meaningful.
- Morning vaccination did not provide a consistent advantage over afternoon vaccination in preventing influenza.
- The time of vaccination was not associated with the risk of influenza-related hospitalization.
The researchers concluded that the effectiveness of influenza vaccination appears to be similar regardless of the time of day it is administered. They noted that future studies could explore whether appointment timing affects the likelihood of getting vaccinated rather than vaccine effectiveness itself.
Reference:
Wong KK, Jena AB. Time of Day of Influenza Vaccination and Subsequent Influenza Risk. JAMA Netw Open. 2026;9(7):e2625267. doi:10.1001/jamanetworkopen.2026.25267
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