Background 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. Methods 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. Results 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. Conclusions 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.

中文翻译：

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静脉注射2019冠状病毒病（COVID-19）mRNA疫苗可诱发小鼠模型急性心肌心包炎


背景 接种 2019 年冠状病毒病 (COVID-19) 信使 RNA (mRNA) 疫苗后，有报道出现接种后心肌心包炎。无意中静脉注射这种疫苗对心脏的影响尚不清楚。方法 比较Balb/c小鼠静脉（IV）或肌内（IM）注射生理盐水（NS）疫苗后不同时间点的临床表现、组织病理学变化、组织mRNA表达量以及血清细胞因子/趋化因子和肌钙蛋白水平。控制。结果 虽然注射后1-2天（dpi）IM组体重明显减轻，血清细胞因子/趋化因子水平升高，但只有IV组出现心肌心包炎的组织病理学改变，表现为心肌细胞变性、凋亡和坏死，并伴有邻近炎症。尽管没有冠状动脉或其他心脏病的证据，但脏层心包上有细胞浸润和钙化沉积。 IV组血清肌钙蛋白水平显着升高。免疫染色偶尔会在心脏或注射部位的浸润性免疫细胞、心肌细胞和心内血管内皮细胞中发现严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 尖峰抗原表达，但在骨骼肌细胞中则不然。第一次 IV 预冲剂量后心肌心包炎的组织学变化持续 2 周，第二次 IM 或 IV 加强剂量后明显加剧。 IV组心肌组织中白细胞介素(IL)-1β、干扰素(IFN)-β、IL-6和肿瘤坏死因子(TNF)-α的mRNA表达从1dpi到2dpi显着增加，但IM组没有显着增加。与 IV 组中存在心肌心包炎相一致。 在 IV 组中始终发现肝细胞气球样变性。所有其他器官均显示正常。结论 本研究提供了体内证据，表明无意中静脉注射 COVID-19 mRNA 疫苗可能诱发心肌心包炎。短暂抽出注射器柱塞以排除血液吸入可能是降低此类风险的一种可能方法。