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 |
| . | 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.
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 |
| . | 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.
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