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Table 1.

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

Pathology amRNA 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.