Impact of sleep duration on the response to vaccination: A meta-analysis

ABSTRACT

Introduction: The SARS-COV-2 pandemic has resulted in over than 5 millions confirmed deaths. Although vaccination is a major strategy to control this pandemic, to date, only 54% of the world population has received at least one dose of a COVID-19 vaccine. Booster inoculations are increasingly recommended. Thus, the vaccination effort may need to continue for several years before the epidemic can be considered as contained. Although antibody response is just one facet of the adaptive immune system’s response to vaccination, it is considered to be a clinically significant biomarker of protection. The role of insufficient sleep duration in individual differences in antibody responses to vaccination against influenza or hepatitis has been examined in a number of studies, with somewhat mixed results. In order to summarize and clarify these findings, we have used a meta-analytical approach to determine whether the current body of evidence suggests that optimizing sleep duration may be an easily modifiable behavior that could increase the efficacy of anti-viral vaccination. Materials and Methods: The PubMed database was searched with the combination “sleep*” and “vaccin*” keywords. Studies were selected if they met the following criteria (1) were performed on healthy human adults;(2) assessed vaccine efficacy by antibody titers or protection status;(3) performed subjective (survey items, questionnaire, sleep diary, interview) and/or objective (actigraphy, polysomnography) measures of sleep duration;(4) were laboratory-conducted studies of manipulation of sleep duration over 1 or more nights;(5) were cohort studies;(6) were peer reviewed original research papers. Since the number of available studies was small, we have engaged in a collaborative effort with the authors of all publications to obtain the information needed to optimize the estimation of the pooled effect size (ES) and the 95% confidence intervals log transformed data when non parametric testing was used;calculation of separate ES for men and women;analyses corrected for age and overweight/obesity status whenever appropriate;sleep data no more than one week apart from inoculation. Number of participants, mean, beta or odd ratio and their respective dispersion were collected. The ES was interpreted as small when ≤0.20, moderate when >0.50 - ≤ 0.80 or large when >0.80. Results: No relationship was observed between self-reported short sleep and vaccine efficacy (n=504;overall ES=0.16 [-0.12, 0.44]). In contrast, when studies that used objective measures of sleep were examined, a robust adverse impact of short sleep on vaccine efficacy was detected (n=282;overall ES=0.96 [0.15, 1.78]). The pooled ES for experimental studies (n=111) was 0.84 [0.20, 1.49] and 1.08 [0.10, 2.06] for prospective studies (n=171). The meta-analysis did not find significant differences in ES between women and men. Conclusions: When assessed objectively, short sleep duration was associated with a clinically relevant decrease in efficacy of anti-viral vaccination. These findings suggest that achieving adequate amount of sleep during the time window surrounding the time of inoculation may increase the efficacy of vaccines against diverse strains of viruses, possibly including strains of SARS-CoV-2. Acknowledgements Collectively, the authors acknowledge the support of their respective institutions in these challenging times.