Diurnal rhythms in varicella vaccine effectiveness

BACKGROUND: Immune processes are influenced by circadian rhythms. We evaluate the association between varicella vaccine administration time of day and vaccine effectiveness. METHODS: A national cohort, children younger than 6 years, were enrolled between January 2002 and December 2023. We compared children vaccinated during morning (7:00–10:59), late morning to afternoon (11:00–15:59), or evening hours (16:00–19:59). A Cox proportional hazards regression model was used to adjust for ethnicity, sex, and comorbidities. The first varicella infection occurring at least 14 days after vaccination and a second dose administration were treated as terminal events. RESULTS: Of 251,141 vaccinated children, 4,501 (1.8%) experienced breakthrough infections. Infection rates differed based on vaccination time, with the lowest rates associated with late morning to afternoon (11:00–15:59), HR 0.88, 95% CI 0.82–0.95, P < 0.001, and the highest rates with evening vaccination (16:00–19:59), HR 1.41, 95% CI 1.32–1.52, P < 0.001. Vaccination timing remained significant after adjustment for ethnicity, sex, and comorbidities. The association between immunization time and infection risk followed a sinusoidal pattern, consistent with a diurnal rhythm in vaccine effectiveness. CONCLUSION: We report a significant association between the time of varicella vaccination and its clinical effectiveness. Similar association was observed with the COVID-19 vaccine, providing proof of concept consistent with a diurnal rhythm in vaccine effectiveness.