Sleep and circadian rhythms are closely involved in the immune system and its regulation. Here, we describe this relationship and provide recommendations regarding the influence of sleep and circadian rhythms on vaccination success. We review studies investigating how viral susceptibility is influenced by changes in immunological parameters as a consequence of sleep deprivation. Short sleep duration and poor sleep efficiency both appear to be strong factors leading to greater vulnerability. In addition, both sleep duration and the time of day of the vaccination seem to be associated with the magnitude of the antibody response after vaccination. Based on these findings, a recommendation would consist of a sleep duration of 7 h or more every night to both reduce the risk of infection and to optimize the efficacy of vaccination with respect to circadian timing. Improving sleep quality and its circadian timing can potentially play a role in preventing infection and in vaccination benefits. In conclusion, sufficient (or longer) sleep duration is important in both reducing susceptibility to infection and increasing antibody response after vaccination.

Summary: This protocol describes an innovative study to investigate the relationship between sleep, shift work and the immune response to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2; coronavirus disease 2019 [COVID‐19]) vaccination. As the COVID‐19 pandemic is a global crisis with devastating health, social and economic impacts, there is a pressing need for effective vaccination programmes. Previous influenza and hepatitis vaccination studies suggest that lack of sleep can negatively alter immune responsiveness, while circadian misalignment most likely may also play an important role in the immune response to vaccination. Our present study will be the first to address this question in actual shift workers and in relation to COVID‐19 vaccination. We hypothesise that the occurrence of recent night shifts and diminished sleep will negatively alter the immune response to vaccination in shift workers compared to dayworkers. We aim to recruit 50 shift workers and 50 dayworkers. Participants will receive an mRNA‐based vaccination, through the Dutch vaccination programme. To assess immune responsiveness, blood will be drawn at baseline (before first vaccination), 10 days after first vaccination, the day prior to the second vaccination; and 28 days, 6 and 12 months after the second vaccination. Actigraphy and daily sleep e‐diaries will be implemented for 7 days around each vaccination to assess sleep. The Pittsburgh Sleep Quality Index will be used to monitor sleep in the long term. Optimising the efficacy of the COVID‐19 vaccines is of outmost importance and results of this study could provide insights to develop sleep and circadian‐based interventions to enhance vaccination immunity, and thereby improve global health.

This study aimed to examine prospectively whether individual nighttime sleep characteristics at baseline (prior to shift‐work exposure) are related to parameters of daytime sleep after commencing shift work. A longitudinal field study was carried out with novice police officers of the Dutch Police Force. A total of 26 subjects were examined at baseline before they entered shift work and re‐examined during follow‐up sessions after four and twelve months of shift‐work exposure. Wrist actigraphy and sleep diaries were used to study nocturnal sleep at baseline and daytime sleep after night shifts during follow‐up sessions. As outcome variables, estimated total sleep time, sleep efficiency, and subjective sleep quality were analyzed. Daytime total sleep time showed a 66 min decline during the first year of shift‐work exposure. Systematic inter‐individual differences were observed for daytime total sleep time and subjective sleep quality (explaining 53% and 38% of the variance, respectively), suggesting potential predictability of these sleep parameters. Although no predictors were found for daytime total sleep time, the subjective quality of nighttime sleep before the onset of shift work predicted 40% of the variance in the subjective quality of daytime sleep after commencing shift work. Follow‐up studies may reveal whether the subjective quality of baseline nighttime sleep also predicts long‐term overall tolerance for shift work.

Circadian misalignment remains a distinct challenge for night shift workers. Variability in individual sleep-wake/light-dark patterns might contribute to individual differences in circadian alignment in night shift workers. In this simulation study, we compared the predicted phase shift from a mathematical model of the effect of light on the human circadian pacemaker to the observed melatonin phase shift among individuals who completed one of four interventions during simulated night shift work. Two inputs to the model were used to simulate circadian phase: sleep-wake/light-dark patterns measured from a wrist monitor (Simulation 1) and sleep-wake/light-dark patterns measured from a wrist monitor enhanced by known light levels measured at the level of the eye during simulated night shifts (Simulation 2). The estimated phase shift from the model was within 2 hours of the observed phase shift in ~80% of night shift workers for both simulations; none of the model-predicted phase shifts was more than ~3 hours from the observed phase shift. Overall, the root-mean-square error between observed and predicted phase shifts was better for Simulation 1. The light input from the wrist monitor informed by actual light level measured at the eye performed better in the sub-group exposed to bright light during their night shifts. The findings from this simulation study suggest that using a mathematical model combined with sleep-wake and light exposure data from a wrist monitor can facilitate the design of shift work schedules to enhance circadian alignment, which is expected to improve sleep, alertness, and performance.