Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
BMJ. 2022 Jul 13;378:e070483. doi: 10.1136/bmj-2022-070483.
To assess the risk of adverse events associated with heterologous primary (two dose) and booster (three dose) vaccine schedules for covid-19 with Oxford-AstraZeneca's ChAdOx1-S priming followed by mRNA vaccines (Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273) as compared with homologous mRNA vaccine schedules for covid-19.
Nationwide cohort study.
Denmark, 1 January 2021 to 26 March 2022.
Adults aged 18-65 years who received a heterologous vaccine schedule of priming with ChAdOx1-S and one or two mRNA booster doses (with either the BNT162b2 or mRNA-1273 vaccine) were compared with adults who received a homologous BNT162b2 or mRNA-1273 vaccine schedule (ie, two dose two dose, and three dose three dose schedule).
The incidence of hospital contacts for a range of adverse cardiovascular and haemostatic events within 28 days after the second or third vaccine dose, comparing heterologous versus homologous vaccine schedules. Secondary outcomes included additional prioritised adverse events of special interest. Poisson regression was used to estimate incidence rate ratios with adjustment for selected covariates.
Individuals who had had a heterologous primary vaccine (n=137 495) or a homologous vaccine (n=2 688 142) were identified, in addition to those who had had a heterologous booster (n=129 770) or a homologous booster (n=2 197 213). Adjusted incidence rate ratios of adverse cardiovascular and haemostatic events within 28 days for the heterologous primary and booster vaccine schedules in comparison with the homologous mRNA vaccine schedules were 1.22 (95% confidence interval 0.79 to 1.91) and 1.00 (0.58 to 1.72) for ischaemic cardiac events, 0.74 (0.40 to 1.34) and 0.72 (0.37 to 1.42) for cerebrovascular events, 1.12 (0.13 to 9.58) and 4.74 (0.94 to 24.01) for arterial thromboembolisms, 0.79 (0.45 to 1.38) and 1.09 (0.60 to 1.98) for venous thromboembolisms, 0.84 (0.18 to 3.96) and 1.04 (0.60 to 4.55) for myocarditis or pericarditis, 0.97 (0.45 to 2.10) and 0.89 (0.21 to 3.77) for thrombocytopenia and coagulative disorders, and 1.39 (1.01 to 1.91) and 1.02 (0.70 to 1.47) for other bleeding events, respectively. No associations with any of the outcomes were found when restricting to serious adverse events defined as stay in hospital for more than 24 h.
Heterologous primary and booster covid-19 vaccine schedules of ChAdOx1-S priming and mRNA booster doses as both second and third doses were not associated with increased risk of serious adverse events compared with homologous mRNA vaccine schedules. These results are reassuring but given the rarity of some of the adverse events, associations cannot be excluded.
评估与牛津-阿斯利康腺病毒载体 ChAdOx1-S 初免和信使 RNA（mRNA）疫苗加强针（两针或三针）相比，新冠病毒疫苗异源初免和加强免疫方案（两针或三针）与同源 mRNA 疫苗方案相比，与新冠病毒相关的不良事件风险。
全国性队列研究。
丹麦，2021 年 1 月 1 日至 2022 年 3 月 26 日。
18-65 岁的成年人，接受 ChAdOx1-S 初免和一剂或两剂 mRNA 加强针（分别使用 BNT162b2 或 mRNA-1273 疫苗）的异源疫苗方案与接受同源 BNT162b2 或 mRNA-1273 疫苗方案（即两针两针和三针三针方案）的成年人进行比较。
在第二次或第三次疫苗接种后 28 天内，比较异源与同源疫苗方案，评估一系列不良心血管和止血事件的医院接触发生率。次要结局包括其他重点关注的不良事件。使用泊松回归估计调整选定协变量后的发病率比值比。
确定了接受异源初级（n=137495）或同源疫苗（n=2688142）以及接受异源加强针（n=129770）或同源加强针（n=2197213）的个体。与同源 mRNA 疫苗方案相比，异源初级和加强免疫疫苗方案 28 天内不良心血管和止血事件的调整发病率比值比为 1.22（95%置信区间 0.79 至 1.91）和 1.00（0.58 至 1.72），缺血性心脏事件为 0.74（0.40 至 1.34）和 0.72（0.37 至 1.42），脑血管事件为 1.12（0.13 至 9.58）和 4.74（0.94 至 24.01），动脉血栓栓塞事件为 1.12（0.13 至 9.58）和 4.74（0.94 至 24.01），静脉血栓栓塞事件为 0.79（0.45 至 1.38）和 1.09（0.60 至 1.98），心肌炎或心包炎为 0.84（0.18 至 3.96）和 1.04（0.60 至 4.55），血小板减少症和凝血障碍为 0.97（0.45 至 2.10）和 0.89（0.21 至 3.77），其他出血事件为 1.39（1.01 至 1.91）和 1.02（0.70 至 1.47）。当将严重不良事件（定义为住院超过 24 小时）限制为严重不良事件时，与任何结果均无关联。
与同源 mRNA 疫苗方案相比，ChAdOx1-S 初免和 mRNA 加强针（两针或三针）的新冠病毒异源初免和加强免疫方案与新冠病毒相关的不良事件风险无显著增加。这些结果令人放心，但由于某些不良事件的罕见性，仍不能排除关联。
