Biological rhythms in COVID-19 vaccine effectiveness in an observational cohort study of 1.5 million patients.
Biological rhythms in COVID-19 vaccine effectiveness in an observational cohort study of 1.5 million patients.
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DOI：
10.1172/jci167339
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发表时间：
2023-06-01
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昼夜节律在基本免疫过程中很明显，但尚不清楚疫苗保护等临床终点是否存在节律。在这里，我们研究了 COVID-19 疫苗接种时机和有效性之间的关联。我们回顾性分析了一个接种了带有时间戳的 COVID-19 疫苗的以色列大型队列（n = 1,515,754 名 12 岁以上患者，其中 99.2% 接受了 BNT162b2）。终点包括 COVID-19 突破性感染以及与 COVID-19 相关的急诊科就诊和住院治疗。我们的主要比较是在早上（800-1159 小时）、下午（1200-1559 小时）或晚上（1600-1959 小时）接种疫苗的患者。我们采用 Cox 回归来调整年龄、性别和合并症的差异。突破性感染因疫苗接种时间而异，上午晚些时候至下午早些时候的感染率最低，而晚上疫苗接种的感染率最高。在调整患者年龄、性别和合并症后，疫苗接种时机仍然很重要。接受基础 2 剂系列治疗和接受加强剂量治疗的患者的结果是一致的。 COVID-19 免疫时间与突破性感染之间呈正弦关系，与使疫苗有效性改变 8.6%–25% 的生物节律一致。日间疫苗接种的益处集中在年轻患者（<20 岁）和老年患者（>50 岁）中。 COVID-19 相关住院治疗随第二次加强剂量的时间安排存在显着差异，这是一种针对老年和免疫抑制患者的干预措施（HR = 0.64，早上与晚上；95% CI，0.43–0.97；P = 0.038）。我们报告了 COVID-19 疫苗接种时间与其有效性之间存在显着关联。这对大规模疫苗接种计划具有影响。 NIH。
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. 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. 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 (<20 years old) and older patients (>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). We report a significant association between the time of COVID-19 vaccination and its effectiveness. This has implications for mass vaccination programs. NIH.
DOI：
10.3390/v14081728
发表时间：
2022-08-05
期刊：
Viruses
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