Abstract [275 words] Background: Seasonal disease outbreaks are perennial features of human infectious disease but the factors generating these patterns are unclear. In animal studies, seasonal and circadian (daily) rhythms in immune function generate periodicity in vulnerability to disease, although it is not known whether the same applies to humans. Making use of extensive data from the UK Biobank cohort, we investigate seasonal and daytime variability in multiple immune parameters (inflammatory markers, white blood cell counts and antibody titres), and test for associations with a wide range of environmental and lifestyle factors. Methods and Findings: Markers of inflammation (CRP), and white blood cell counts were measured between 8am and 7pm over a 4-year time period in 329,261 participants in UK Biobank. Individual-level data were linked to other factors that vary over seasonal and daily cycles, including changes in day length, outdoor temperature and vitamin D at the time the blood sample was collected. Analyses were further adjusted for potentially confounding lifestyle factors. Seasonal patterns were evident in lymphocyte and neutrophil counts, and CRP, but not monocytes, and these were independent of lifestyle, demographic and environmental factors. All the immune parameters assessed demonstrated significant daytime variation that was independent of confounding factors. Conclusions: At a population level, human immune parameters vary across season and across time of day, independent of multiple confounding factors. Both season and time of day are fundamental dimensions of immune function that should be considered in all studies of immuno-prophylaxis and disease transmission. Strategic alignment of human activities to seasons and times of the day when we are less susceptible to infection could be an important additional tool for limiting population-level impacts of infectious diseases.
Seasonal and Daytime Variation in Multiple Immune Parameters in Humans: Evidence from 329,261 Participants of the UK Biobank Cohort