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Objectives:  Shift work may be associated with an increased incidence of respiratory infections. However, underlying mechanisms are unclear. Therefore, our aim was to examine the mediating role of sleep, physical activity, and diet in the association between shift work and respiratory infections.    Methods:  This prospective cohort study included 396 shift and non-shift workers employed in hospitals. At baseline, sleep duration and physical activity were measured using actigraphy and sleep/activity diaries, sleep quality was reported, and frequency of meal and snack consumption was measured using food diaries. In the following six months, participants used a smartphone application to report their influenza-like illness/acute respiratory infection (ILI/ARI) symptoms daily. Mediation analysis of sleep, physical activity, and diet as potential mediators of the effect of shift work on ILI/ARI incidence rate was performed using structural equation modeling with negative binomial and logistic regression.    Results:  Shift workers had a 23% [incidence rate ratio (IRR) 1.23, 95% CI 1.01–1.49] higher incidence rate of ILI/ARI than non-shift workers. After adding the potential mediators to the model, this reduced to 15% (IRR 1.15, 95% CI 0.94–1.40). The largest mediating (ie, indirect) effect was found for poor sleep quality, with shift workers having 29% more ILI/ARI episodes via the pathway of poorer sleep quality (IRR 1.29, 95% CI 1.02–1.95).    Conclusions:  Compared to non-shift workers, shift workers had a higher incidence rate of ILI/ARI that was partly mediated by poorer sleep quality. Therefore, it may be relevant for future research to focus on perceived sleep quality as an underlying mechanism in the relation between shift work and increased infection susceptibility.

The mediating role of sleep, physical activity, and diet in the association between shift work and respiratory infections