Objective To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines. Design International network cohort study. Setting Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US. Participants Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021. Main outcome measures Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses. Results Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2. Conclusions In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development. Patient level data cannot be shared without approval from data custodians owing to local information governance and data protection regulations. The analytical code is available at: . Additional correspondence and requests for materials should be addressed to the corresponding author (EB).

中文翻译：

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与不同 covid-19 疫苗相关的血栓形成与血小板减少综合征或血栓栓塞事件的比较风险：来自五个欧洲国家和美国的国际网络队列研究

目的 量化与使用基于腺病毒的 covid-19 疫苗与基于 mRNA 的 covid-19 疫苗相关的血栓形成伴血小板减少综合征或血栓栓塞事件的比较风险。设计国际网络队列研究。设置 从法国、德国、荷兰、西班牙、英国和美国的贡献数据集中定期收集健康数据。参与者 成人（年龄≥18 岁）在任何贡献数据库中注册并接受了至少一剂 covid-19 疫苗（ChAdOx1-S（Oxford-AstraZeneca）、BNT162b2（Pfizer-BioNTech）、mRNA-1273（Moderna）、或 Ad26.COV2.S (Janssen/Johnson & Johnson)），从 2020 年 12 月到 2021 年年中。主要结果测量 covid-19 疫苗接种后 28 天内血栓形成伴血小板减少综合征或静脉或动脉血栓栓塞事件。在倾向得分匹配后估计发病率比率，并使用阴性对照结果进行校准。通过使用随机效应荟萃分析汇总了特定于数据库的估计值。结果总体而言，3 829 822 名首剂 ChAdOx1-S 接受者中的 1 332 719 名与来自德国和英国的 2 149 679 名 BNT162b2 接受者中的 2 124 339 名匹配。此外，在德国、西班牙和美国，接受 Ad26.COV2.S 的 772 678 人中有 762 517 人与接受 BNT162b2 的 7 606 693 人中有 2 851 976 人相匹配。来自美国的所有 628 164 名 Ad26.COV2.S 受体均与 3 923 371 名 mRNA-1273 受体中的 2 230 157 名相匹配。在来自德国和英国的匹配的首剂 ChAdOx1-S 受体中，共观察到 862 起血小板减少事件，在首剂 BNT162b2 后观察到 520 起事件。将 ChAdOx1-S 与第一剂 BNT162b2 进行比较显示血小板减少症的风险增加（合并校准发病率比 1.33（95% 置信区间 1.18 至 1.50）和校准发病率差异为每 1000 人年 1.18（0.57 至 1.8））。此外，与 BNT162b2 相比，Ad26.COV2.S 与血小板减少综合征的静脉血栓形成的合并校准发病率比为 2.26（0.93 至 5.52）。结论 在这项多国研究中，观察到首剂 ChAdOx1-S 疫苗后血小板减少症的风险增加 30%，与 BNT162b2 相比，Ad26.COV2.S 后血小板减少症综合征的静脉血栓形成风险增加的趋势. 虽然很少见，在规划进一步的免疫接种活动和未来的疫苗开发时，应考虑使用基于腺病毒的疫苗后观察到的风险。由于当地信息治理和数据保护法规，未经数据保管人批准，不能共享患者级别的数据。分析代码可在以下位置获得：. 其他通信和材料请求应发送给通讯作者 (EB)。