Table 1.

Summary of the Pathological Changes in Heart and Liver After IV or IM Administration of mRNA Vaccine

	Pathology a	mRNA Vaccine Injection (Second Dose Given 14 days After First Dose)
	Changes (Related Figures)	2 dpi First IV Dose n = 13 (%)	2 dpi First IM Dose n = 6 (%)	NS 2dpi n = 12 (%)	2 dpi Second IV Dose n = 9 (%)	2 dpi Second IMDosen = 6 (%)
Heart	Grossly visible white patches on visceral pericardium (Fig 1C, 1D)	5/13 (38.5%)†	0/6	0/12	3/9 (33.3%)	1/6 (16.7%)
	Pericardial calcific deposit (Fig. 2A, 2D)	5/13 (38.5%)†	0/6	0/12	4/9 (44.4%)†	2/6 (33.3%)
	Pericardial WBC infiltration (Fig. 2C)	9/13 (69.2%)* ,†††	0/6	0/12	5/9 (55.6%)††	2/6 (33.3%)
	Myocardial WBC infiltration (Fig. 2C, 2G)	8/13 (61.5%)* ,†††	0/6	0/12	9/9 (100%)†††	6/6 (100%)†††
	Cardiomyocytes degeneration Fig. 2E)	8/13 (61.5%)††	2/6 (33.3%)	0/12	9/9 (100%)†††	6/6 (100%)†††
	Cardiomyocytes necrosis (Fig. 2F)	4/13 (30.8%)	0/6	0/12	9/9 (100%)†††	6/6 (100%)†††
	Cardiomyocytes apoptosis (Fig. 3B)	5/13 (38.5%)†	0/6	0/12	ND	ND
	Spike RBD expression b (Fig. 4A, 4B)	3/8 (37.5%)†	0/6	0/12	ND	ND
	Serum troponin (pg/mL)c	1328.2 ± 325.8**** ,††††	237.5 ± 121.2	215 ± 115.9	ND	ND
Liver	Grossly visible change at autopsy	0/6	0/6	0/6	0/9	0/6
	Hepatocytes ballooning degeneration (Fig. 8A)	6/6 (100%)††	3/6 (50%)	0/6	ND	ND
	Hepatocytes necrosis	2/6 (50%)	0/6	0/6	ND	ND

Abbreviations: dpi, days post-injection; IM, intramuscular; IV, intravenous; ND, not done; NS, normal saline; RBD, receptor binding domain; WBC, white blood cells.

^a Presented as the number and percentage of mice with positive gross or histological changes in the heart and liver.

^b Number heart sections showed RBD positive cells at 1 dpi.

^c Serum troponin concentration in mouse serum were determined by Enzyme Immunoassay using Mouse CTNI (Cardiac troponin-I) ELISA Kit (Mybiosource, San Diego, California, USA).

* P < .05,**** P < .0001 when compared to IM group at the same time point.

† P < .05, ††P < .01, †††P < .001, ††††P < .0001 when compared to NS 2 dpi group.