A new study published in JAMA Network Open found that the hour of day when a patient receives an influenza vaccine has no clinically meaningful bearing on how well that vaccine protects them. The analysis included data from over 23 million vaccinations administered to nearly 15.9 million individuals between August 2023 and January 2026.
The idea that time of day could influence vaccine performance isn’t new, as circadian rhythms are known to modulate immune function. Several small studies have shown differences in antibody response depending on whether vaccination occurred in the morning or afternoon.
Study Design and Methodology
Researchers Karen K. Wong, MD, MPH, of Epic Systems, and Anupam B. Jena, MD, PhD, of Harvard Medical School, used de-identified electronic health record data from Cosmos, a network spanning more than 300 health systems. The analysis included adults 18 years and older who received a single dose of influenza vaccine between 7 am and 5 pm.
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To account for potential confounders, the investigators ran a within-person analysis, comparing the same individual’s outcomes when vaccinated at different hours across different years, controlling for age and person-level fixed effects.
Key Findings
Vaccination volume peaked between 8 am and 10 am, with a smaller second peak between noon and 2 pm. The study found that hour of vaccination showed no significant association with influenza-related hospitalization risk.
While the biological plausibility of a circadian effect on immune response remains supported by mechanistic and small-cohort data, that effect does not appear to translate into a real-world difference in whether patients ultimately get sick with flu.
The findings arrive against a backdrop of a 2025-2026 flu season with lower-than-usual vaccine effectiveness, driven largely by a drifted influenza A(H3N2) subclade circulating this year. Interim CDC estimates place vaccine effectiveness against medically attended illness in a more modest range than in recent seasons.
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In practice, this means that pharmacists can focus on maximizing vaccine uptake and matching antigenic strains, rather than optimizing appointment scheduling. The study authors suggest that clinical effort is better spent understanding whether appointment time affects the likelihood that a patient shows up for vaccination at all, rather than how well the vaccine works once administered.
The study’s results are reassuring for pharmacists, indicating that there is no evidence-based reason to steer patients toward morning appointments or to worry that an afternoon or evening walk-in vaccination is inferior. This matters operationally, since pharmacy-based immunization scheduling already has to balance patient convenience, walk-in volume, and staffing.
As the flu season continues, the priority now shifts to understanding how to improve vaccine uptake and effectiveness, rather than optimizing appointment scheduling. The study’s findings provide valuable insights for healthcare professionals and patients alike, highlighting the importance of maximizing vaccine uptake and matching antigenic strains.
