Circadian Variation in the Response to Vaccination: A Systematic Review and Evidence Appraisal.

Molecular timing mechanisms known as circadian clocks drive endogenous 24-h rhythmicity in most physiological functions, including innate and adaptive immunity. Consequently, the response to immune challenge such as vaccination might depend on the time of day of exposure. This study assessed whether the time of day of vaccination (TODV) is associated with the subsequent immune and clinical response by conducting a systematic review of previous studies. The Cochrane Library, PubMed, Google, Medline, and Embase were searched for studies that reported TODV and immune and clinical outcomes, yielding 3114 studies, 23 of which met the inclusion criteria. The global severe acute respiratory syndrome coronavirus 2 vaccination program facilitated investigation of TODV and almost half of the studies included reported data collected during the COVID-19 pandemic. There was considerable heterogeneity in the demography of participants and type of vaccine, and most studies were biased by failure to account for immune status prior to vaccination, self-selection of vaccination time, or confounding factors such as sleep, chronotype, and shiftwork. The optimum TODV was concluded to be afternoon (5 studies), morning (5 studies), morning and afternoon (1 study), midday (1 study), and morning or late afternoon (1 study), with the remaining 10 studies reporting no effect. Further research is required to understand the relationship between TODV and subsequent immune outcome and whether any clinical benefit outweighs the potential effect of this intervention on vaccine uptake.

Susceptibility to the common cold virus is associated with day length.

Seasonal rhythms are endogenous timing mechanisms that allow animals living at temperate latitudes to synchronize their physiology to the seasons. Human viral respiratory disease is prevalent in the winter at temperate latitudes, but the role of endogenous mechanisms in these recurring annual patterns is unclear. The Common Cold Project is a repository of data describing the experimental viral challenge of 1,337 participants across the seasons of the year. We report a secondary analysis of these data to investigate if susceptibility to the common cold is associated with day length. The majority of the participants (78%) showed signs of infection but only 32% developed clinical signs of disease, and the probability of infection was significantly higher in longer day lengths (summer), but the disease was more likely in short (winter) day lengths. The persistence of winter disease patterns in experimental conditions supports the role of endogenous seasonality in human susceptibility to viral infection.