First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales.
First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales.
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DOI：
10.1371/journal.pmed.1003927
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发表时间：
2022-03
期刊：
影响因子：
15.8
通讯作者：
Sheikh A
中科院分区：
文献类型：
--
作者：
Kerr S;Joy M;Torabi F;Bedston S;Akbari A;Agrawal U;Beggs J;Bradley D;Chuter A;Docherty AB;Ford D;Hobbs R;Katikireddi SV;Lowthian E;de Lusignan S;Lyons R;Marple J;McCowan C;McGagh D;McMenamin J;Moore E;Murray JK;Owen RK;Pan J;Ritchie L;Shah SA;Shi T;Stock S;Tsang RSM;Vasileiou E;Woolhouse M;Simpson CR;Robertson C;Sheikh A
2021年，几个国家将ChAdOx 1的给药限制在老年人群中，原因是病例报告和观察与预期分析表明可能与脑静脉窦血栓形成（CVST）相关的安全性问题。由于2019冠状病毒病（COVID-19）疫苗接种和CVST事件的极端罕见性，需要大型数据集来精确估计两者之间的关联。我们的目标是通过结合英格兰、苏格兰和威尔士的国家数据来实现这一目标。我们创建了数据平台，包括英格兰、苏格兰和威尔士的相关初级保健、二级保健、死亡率和病毒学检测数据，合并队列11，637，157人，随访6，808，293人年。队列开始日期为2020年12月8日，结束日期为2021年6月30日。我们检查的结果指标是记录在初级或二级保健记录中的CVST事件。我们对首次接种ChAdOx 1和BNT 162 b2疫苗后的结果进行了自身对照病例系列（SCCS）分析。观察期包括最初的90天参考期，随后是疫苗接种前2周的风险前期和疫苗接种后4周的风险期。对每个国家的CVST病例计数进行统计，然后扩展为一个完整的数据集，每个个体和观察时间段各1行。队列中共有201例CVST事件（29.5/百万人年）。在观察期内，在接受第一剂ChAdOx 1的患者中有81例CVST事件（约16.34/百万剂量），在接受第一剂BNT 162 b2的患者中有40例CVST事件（约12.60/百万剂量）。我们拟合条件泊松模型来估计发病率比（IRR）。ChAdOx 1疫苗接种与疫苗接种后28天内CVST事件发生风险升高相关，IRR = 1.93（95%置信区间（CI）1.20 - 3.11）。在接种疫苗后28天内，我们没有发现BNT 162 b2与CVST之间的关联，IRR = 0.78（95%CI 0.34至1.77）。我们的研究有一些局限性。SCCS研究设计隐式控制了观察期内恒定的变量，但也假设结局事件与暴露无关。在CVST的情况下，这一假设可能不满足，首先是因为它是一种严重的不良事件，其次是因为英国的疫苗接种计划优先考虑临床上极其脆弱的人群和具有基础健康状况的人群，这可能对更容易发生CVST的个体产生选择效应。尽管我们汇集了来自几个大型数据集的数据，但事件数量仍然很少，这可能导致我们的估计不精确。在这项研究中，我们观察到接种ChAdOx 1疫苗后CVST事件的风险略有升高，但BNT 162 b2没有。我们的分析汇集了来自英格兰，苏格兰和威尔士的大型数据集的信息。这一证据可能有助于疫苗政策的风险效益分析，并为公众提供与疫苗接种相关的风险量化。在一项汇总的自我对照病例系列研究中，Steven Kerr及其同事评估了英格兰、苏格兰和威尔士首次接种ChAdOx 1和BNT 162 b2 COVID-19疫苗与脑静脉窦血栓形成之间的关联。有迹象表明，2019冠状病毒病（COVID-19）疫苗-特别是牛津/阿斯利康（ChAdOx 1）-与脑静脉窦血栓形成（CVST）之间可能存在关联，CVST是一种罕见的大脑血块。需要关于这一主题的进一步证据，以便为疫苗政策的审议提供信息。我们估计了第一剂疫苗接种后4周内CVST事件的发生率，并与疫苗接种前90天的发生率进行了比较。接种Oxford/AstraZeneca疫苗后4周内的CVST事件发生率约为基线发生率的两倍，这意味着在此期间每百万接种疫苗的人平均额外发生0.25起事件。我们未发现Pfizer-BioNTech（BNT 162 b2）与CVST之间存在关联。我们发现了ChAdOx 1首次接种疫苗后CVST风险略微增加的证据，而不是BNT 162 b2。公共卫生当局在向公众传达与COVID-19疫苗相关的益处和风险时，不妨考虑这些证据。我们的研究有一些局限性。虽然队列很大，但CVST是一种极其罕见的事件，这可能导致我们的估计有些不精确。此外，我们的模型假设也有可能未得到满足。
Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales. We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates. In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk–benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public. In a pooled self-controlled case series study, Steven Kerr and colleagues assess the association between first dose ChAdOx1 and BNT162b2 COVID-19 vaccination with cerebral venous sinus thrombosis in England, Scotland and Wales. There have been indications of a possible association between Coronavirus Disease 2019 (COVID-19) vaccines—in particular, Oxford/AstraZeneca (ChAdOx1)—and cerebral venous sinus thrombosis (CVST), which is a rare type of blood clot in the brain. Further evidence on this topic is required in order to inform vaccine policy deliberations. We estimated the rate of CVST events in the 4 weeks following first dose vaccination compared with a 90-day period prior to vaccination. The rate of CVST events in the 4 weeks following vaccination with Oxford/AstraZeneca was approximately twice as high compared to the baseline rate, implying an additional 0.25 events on average in this period per million people vaccinated. We did not find an association between Pfizer-BioNTech (BNT162b2) and CVST. We found evidence of a slight increased risk of CVST following first dose vaccination with ChAdOx1, but not BNT162b2. Public health authorities may wish to take this evidence into account when communicating the benefits and risks associated with COVID-19 vaccines to the general public. Our study had some limitations. Although the cohort was large, CVST is an extremely rare event, and this may have caused some imprecision in our estimates. In addition, there is a possibility that our model assumptions were not satisfied.
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DOI：
10.1016/s0140-6736(20)32661-1
发表时间：
2021-01-09
期刊：
Lancet (London, England)
影响因子：
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作者：
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影响因子：
120.7
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通讯作者：
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DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
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