Intravenous Injection of Coronavirus Disease 2019 (COVID-19) mRNA Vaccine Can Induce Acute Myopericarditis in Mouse Model.

Intravenous Injection of Coronavirus Disease 2019 (COVID-19) mRNA Vaccine Can Induce Acute Myopericarditis in Mouse Model.
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静脉注射冠状病毒疾病2019(COVID-19)mRNA疫苗可在小鼠模型中诱导急性肌肉炎。

DOI:
10.1093/cid/ciab707
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发表时间:
2022-06-10
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
--
通讯作者:
Yuen KY
Yuen KY
中科院分区:
其他
文献类型:
--
作者:
Li C;Chen Y;Zhao Y;Lung DC;Ye Z;Song W;Liu FF;Cai JP;Wong WM;Yip CC;Chan JF;To KK;Sridhar S;Hung IF;Chu H;Kok KH;Jin DY;Zhang AJ;Yuen KY

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据报道,接种后的肌包炎是在接种了2019年冠状病毒病(新冠肺炎)信使核糖核酸疫苗后发生的。无意中静脉注射这种疫苗对心脏的影响尚不清楚。我们比较了Balb/c小鼠静脉注射(IV)和肌肉注射(IM)疫苗后不同时间点的临床表现、组织病理学变化、组织mRNA表达以及细胞因子/趋化因子和肌钙蛋白的水平。注射后1~2天,IM组大鼠体重明显减轻,血清细胞因子/趋化因子水平明显升高,但仅IV组出现心肌细胞变性、凋亡、坏死等心肌组织病理学改变,并伴有邻近的炎细胞浸润和内脏心包钙化沉积,但未见冠状动脉或其他心脏病理改变。静脉注射组血清肌钙蛋白水平明显高于对照组。严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)免疫组织化学染色发现,在心脏或注射部位的免疫细胞、心肌细胞和心内血管内皮细胞中偶见SARS-CoV-2刺突抗原的表达,但骨骼肌细胞中未见表达。肌包炎在第一次静脉注射后的组织学改变持续了2周,第二次肌注或静脉注射明显加重。IL-1β、干扰素-β、IL-6和肿瘤坏死因子-α在静脉注射组大鼠心肌组织中的表达在1dpi至2dpi时显著升高,而IM组则无明显变化,与静脉注射组心包炎的存在相一致。静脉注射组持续可见肝细胞气球样变性。其他器官看起来都正常。本研究提供了无意中静脉注射新冠肺炎基因疫苗可诱发心肌心包炎的体内证据。短暂撤除注射器柱塞以排除抽血可能是降低此类风险的一种可能方法。静脉注射冠状病毒病2019(新冠肺炎)信使核糖核酸疫苗可诱导BALB/c小鼠急性心包炎的大体和组织病理学改变。
Post-vaccination myopericarditis is reported after immunization with coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. The effect of inadvertent intravenous injection of this vaccine on the heart is unknown. We compared the clinical manifestations, histopathological changes, tissue mRNA expression, and serum levels of cytokine/chemokine and troponin in Balb/c mice at different time points after intravenous (IV) or intramuscular (IM) vaccine injection with normal saline (NS) control. Although significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1–2 days post-injection (dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis, and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, although evidence of coronary artery or other cardiac pathologies was absent. Serum troponin level was significantly higher in IV group. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of interleukin (IL)-1β, interferon (IFN)-β, IL-6, and tumor necrosis factor (TNF)-α increased significantly from 1 dpi to 2 dpi in the IV group but not the IM group, compatible with presence of myopericarditis in the IV group. Ballooning degeneration of hepatocytes was consistently found in the IV group. All other organs appeared normal. This study provided in vivo evidence that inadvertent intravenous injection of COVID-19 mRNA vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk. Intravenous injection of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine may induce gross and histopathological changes of acute myopericarditis in Balb/c mice.
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