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

Abstract

Background Post-vaccination myopericarditis is reported after immunization with COVID-19 mRNA-vaccines. The effect of accidental 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 in Balb/c mice at different time points after intravenous(IV) or intramuscular(IM) vaccine injection with normal saline(NS) control. Results Though significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1 to 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, while evidence of coronary artery or other cardiac pathologies was absent. 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 IL-1β, IFN-β, IL-6 and TNF-α increased significantly from 1dpi to 2dpi in IV but not IM group, compatible with presence of myopericarditis in IV group. Ballooning degeneration of hepatocytes was consistently found in 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.

Carditis After COVID-19 Vaccination With a Messenger RNA Vaccine and an Inactivated Virus Vaccine

“…The potential mechanism underlying this observed association between BNT162b2 and carditis is unclear. Of note, a recent animal experiment using a mouse model suggested in vivo evidence that inadvertent intravenous injection of COVID-19 mRNA vaccines may induce carditis ( 39 ). Although the extrapolation of animal research to humans warrants great caution, this finding plausibly suggests the possibility that unintended intravenous injection may be 1 potential mechanism to explain the association.…”

“…Although the extrapolation of animal research to humans warrants great caution, this finding plausibly suggests the possibility that unintended intravenous injection may be 1 potential mechanism to explain the association. This is because no histopathologic changes of carditis were seen in mice randomly allocated to receive intramuscular BNT162b2 injection ( 39 ). Further research is warranted to identify the physiologic response triggered by COVID-19 vaccination in relation to carditis and inform further hypothesis-driven studies.…”

Age-associated SARS-CoV-2 breakthrough infection and changes in immune response in a mouse model

“…A two-dose regimen of vaccination with COVID-19 mRNA Vaccine (BNT162b2, lot number 1B004A, BioNTech, Germany) at a 14-day interval was given by the intramuscular injection of 5 µg/per dose in 50 µl volume [ 12 ]. Control groups were injected with the same volume of normal saline.…”

The histologic and molecular correlates of liver disease in fatal COVID-19 including with alcohol use disorder

“…Although the specific mechanism of spike presentation in the liver needs to be elucidated, once endocytosed by ACE2 positive sinusoidal macrophages, including hepatic stellate cells in the AUD cases, the spike protein induced a pro-inflammatory and hypercoagulable state that would cause hepatocyte dysfunction. Importantly, spike protein alone has been shown to be cytotoxic by multiple groups including in the liver [11] , [24] , [25] . This is not to say that circulating cytokines do not also play a role in hepatic dysfunction, but rather that in situ production of these cytokines clearly is a feature of hepatic dysfunction in severe COVID-19.…”