Autoimmunity elicited by the chemokine response to adenovirus vector vaccines may underlie vaccine-induced immune thrombotic thrombocytopaenia: a hypothesis.
Autoimmunity elicited by the chemokine response to adenovirus vector vaccines may underlie vaccine-induced immune thrombotic thrombocytopaenia: a hypothesis.
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DOI：
10.1002/cti2.1349
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发表时间：
2021
影响因子：
5.8
通讯作者：
French M
中科院分区：
文献类型：
--
作者：
McLean-Tooke A;Lucas M;French M
COVID-19（冠状病毒 19）是一种全球性流行病，在世界各地造成严重的发病率和死亡率。与许多其他传染病一样，疫苗接种已成为预防严重疾病和死亡的公共卫生应对措施的重要组成部分，目前国际上已批准多种不同的疫苗。两种利用改良非复制腺病毒载体的疫苗（阿斯利康牛津疫苗中的黑猩猩 ChAdOx1 和强生疫苗中的人类 Ad26.Cov2.S）已经开发出来并获得临床使用许可。 2021 年 3 月，由于疫苗安全信号引起了担忧，表明与阿斯利康疫苗暂时相关的不寻常血栓事件有所增加。多个小组同时鉴定出先前健康的患者，在阿斯利康疫苗接种后 21 天内出现非典型血栓事件（包括脑窦静脉窦和内脏静脉血栓形成）和血小板减少症的组合。 1-3 就诊时，患者表现出 D-二聚体水平升高、不同程度的通常严重的血小板减少症和纤维蛋白原水平低。尽管没有患者在出现该综合征前几天接受过肝素治疗，但在患者血清中发现了抗血小板因子 4 (PF4)-肝素复合物的抗体，该复合物先前与肝素诱导的血小板减少症 (HIT) 有关。鉴于临床和血清学与 HIT 相似，该病症被命名为疫苗诱导的免疫性血栓性血小板减少症 (VITT)。 2 随后，发现与接种强生疫苗相关的血栓形成和血小板减少症病例与与阿斯利康疫苗接种相关的 VITT 病例具有惊人的相似性。 4 VITT 的确切发病率仍不清楚，但据报道为每 26 500 例阿斯利康疫苗第一剂中 1 例到每 127 300 例阿斯利康疫苗中 1 例之间。 5 截至 2021 年 8 月 18 日，英国药品和保健品监管局（MHRA）已收到与阿斯利康疫苗相关的 417 例伴有血小板减少的血栓事件报告（其中 149 例中心静脉窦血栓形成和 268 例其他血栓栓塞事件）。 6 大多数病例 (89%) 发生在第一剂疫苗接种后，第一剂疫苗接种后的发病率为 15.0%，第二剂接种后降至 1.8%。这些数据还显示了不同年龄的发病率，年轻患者的发病率较高，18-49 岁接种疫苗的发病率为每百万人 20.8 例，而年龄 > 50 岁的疫苗接种率为 10.9 例。总体死亡率高达 17%。截至 2021 年 8 月 19 日，澳大利亚免疫技术咨询小组 (ATAGI) 在接种 810 万剂疫苗后发现了 112 例确诊病例（62 例）或疑似病例（50 例）VITT，预计首剂阿斯利康疫苗后 VITT 发生率为每百万人 29 例
COVID-19 (coronavirus 19) is a global pandemic causing significant morbidity and mortality across the world. As utilised for many other infectious diseases, vaccination has formed the critical component of the public health response for the prevention of severe illness and death with multiple different vaccines now approved internationally. Two vaccinations utilising modified non-replicating adenoviral vectors (Chimpanzee ChAdOx1 in the AstraZeneca Oxford vaccine and Human Ad26. Cov2. S in the Johnson and Johnson vaccine) have been developed and licensed for clinical use. In March 2021, concerns were raised because of vaccine safety signals, suggesting an increase in unusual thrombotic events temporally associated with the AstraZeneca vaccine. Multiple groups simultaneously identified previously well patients presenting within 21 days of an AstraZeneca vaccination with an atypical combination of thrombotic events (including cerebral sinus venous sinus and splanchnic venous thromboses) and thrombocytopaenia. 1–3 At presentation, patients demonstrated elevated D-dimer levels, variable degrees of usually severe thrombocytopaenia and low fibrinogen levels. Antibodies against platelet factor 4 (PF4)-heparin complexes, previously associated with heparininduced thrombocytopaenia (HIT), were identified in patient serum, although none of the patients had received heparin in the days prior to development of the syndrome. Given the clinical and serological resemblance to HIT, the condition was named vaccine-induced immune thrombotic thrombocytopaenia (VITT). 2 Subsequently, cases of thrombosis and thrombocytopaenia related to administration of the Johnson and Johnson vaccine were identified bearing a striking similarity to the VITT cases associated with AstraZeneca vaccination. 4 The exact incidence of VITT remains unknown but is reported to be between 1 case per 26 500 and 1 case per 127 300 first doses of AstraZeneca vaccine. 5 As of 18 August 2021, the Medicine and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom had received reports of 417 thrombotic events with thrombocytopaenia (149 cases of central venous sinus thrombosis and 268 cases of other thromboembolic events) related to the AstraZeneca vaccine. 6 The majority of cases (89%) occurred after the first vaccine dose with an incidence of 15.0 per million after the first dose, dropping to 1.8 per million after the second dose. These data also show different rates with age, with a higher incidence in younger patients with rates of 20.8 per million in vaccines aged 18–49 years versus 10.9 in vaccines aged> 50 years. Overall mortality is high at 17%. As of 19 August 2021, the Australian Technical Advisory Group on Immunisation (ATAGI) had identified 112 cases of confirmed (62 cases) or probable (50 cases) VITT after 8.1 million doses with a rate estimate for VITT after first-dose Astra Zeneca of 29 per million