BACKGROUND. Circadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness. METHODS. We retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19–associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800–1159 hours), afternoon (1200–1559 hours), or evening hours (1600–1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities. RESULTS. Breakthrough infections differed based on vaccination time, with lowest the rates associated with late morning to early afternoon and highest rates associated with evening vaccination. Vaccination timing remained significant after adjustment for patient age, sex, and comorbidities. Results were consistent in patients who received the basic 2-dose series and who received booster doses. The relationship between COVID-19 immunization time and breakthrough infections was sinusoidal, consistent with a biological rhythm that modifies vaccine effectiveness by 8.6%–25%. The benefits of daytime vaccination were concentrated in younger (50 years old). COVID-19–related hospitalizations varied significantly with the timing of the second booster dose, an intervention reserved for older and immunosuppressed patients (HR = 0.64, morning vs. evening; 95% CI, 0.43–0.97; P = 0.038). CONCLUSION. We report a significant association between the time of COVID-19 vaccination and its effectiveness. This has implications for mass vaccination programs. FUNDING. NIH.

The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, an important clinical realization of immune function. Finally, we discuss practical steps to translate circadian immunity to the patient’s bedside.

Background: Inherited metabolic disorders (IMDs) are group of rare monogenic diseases, usually derived from reduced or absent activity in a single metabolic pathway. Most of the IMDs are inherited in an autosomal recessive manner. The incidence of IMDs varies from country to country and within different ethnic groups, but data is still scarce. Consanguinity rate among populations is highly contributor factor for IMDs incidence. There are no reports comparing the incidence of IMD in consanguineous and non-consanguineous populations from the same geographic region with the same diagnostic capabilities. Our study objective is to compare the incidence of IMDs between between the relatively low consanguineous Jewish population and the consanguineous Bedouin population, both living in the southern of Israel. Results: During 1990–2017 there were 393,772 live births in the Negev district, of Southern of Israel. Among them 187,049 were of Jewish origin while 206,723 were of Bedouin-Muslim origin. A total of 223 children were diagnosed in this study period with IMDs. Among those 223 children with IMD, 33 were of Jewish origin while the other 190 children were of Bedouin-Muslim origin. The overall incidence for IMDs of the overall Negev population was 56.6/100,000 live birth. The incidence for IMD's among the Bedouin population was significantly higher than among Jewish population. Conclusions: IMDs are extremely more common in the consanguineous Bedouin compared with the relatively non-consanguineous Jewish population of Southern Israel. Health policy makers should consider these data and prepare educational and genetic counselling problems accordingly.

Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma outcomes remains unclear. This study compares asthma-related healthcare utilization in preschool children born prematurely between those who received Palivizumab (the Prophylaxis (+) group) and those who did not (the Prophylaxis (–) group). Methods: This nationwide, population-based retrospective cohort study utilized data from Clalit Healthcare Services in Israel. The study included children born between 32 + 6 and 34 + 6 weeks of gestational age from 2011 to 2018. Descriptive analysis, univariate analysis, and multivariate logistic regression were performed to compare the Prophylaxis (+) and the Prophylaxis (–) groups. Results: In total, 4503 children were included, with 3287 in the Prophylaxis (+) group and 1216 in the Prophylaxis (–) group. Palivizumab administration was associated with reduced hospitalizations for RSV bronchiolitis (1.8% vs. 3.3%, p = 0.003). However, no significant differences were observed in multivariate analysis for long-term asthma outcomes, including asthma diagnosis (OR = 1.04, CI = 0.84–1.30, p = 0.7) or emergency department visits for asthma (OR = 0.79, CI = 0.54–1.17, p = 0.2). Similarly, Palivizumab administration was not associated with the purchase of short-acting beta-agonists (OR = 1.14, 95% CI 0.98–1.32, p = 0.084), inhaled corticosteroids (OR = 1.1, CI = 0.93–1.32, p = 0.3), or oral corticosteroids (OR = 1.09, CI = 0.94–1.26, p = 0.3). Conclusions: While Palivizumab effectively reduces RSV acute bronchiolitis in preterm infants, it does not significantly impact long-term preschool asthma-related healthcare utilization.