Table 2.
Animal challenge models for SARS-Cov-2 infection
| Species | Challenge dose and route | Pathology | Viral dynamics | Lethal vs non-lethal | Ref. |
|---|---|---|---|---|---|
| Mouse hACE2 (mouse Ace2 promoter) |
IN: 105 TCID50 BetaCoV/Wuhan/IVDC-HB-01/2020 |
Lung pathology peaked 5 dpi | vRNA and infectious titre peaked in the lungs 1–3 and 3 dpi, respectively (102.44 TCID50 in 100 μl) | Non-lethal | 52 |
| Mouse hACE2 (Hfh4 promoter) |
IN: 3 × 104 TCID50 IN: 7 × 105 TCID50 (re-exposure) SARS-CoV-2 isolate USA-WA1/2020 |
Lethal infection with respiratory distress and neurological symptoms Pulmonary lesions peaked 3–5 dpi |
vRNA and infectious titre peaked in the lungs 5 dpi vRNA also detected in the eyes, heart and brain |
Lethal | 45 |
| Mouse hACE2 (K18 promoter) |
IN and IV: 2.5 × 104 PFU 2019n-CoV/USA_WA1/2020 |
Lung pathology peaked 7 dpi Histopathology revealed abnormalities in the brain, heart, liver and kidney of infected mice |
Infectious titre and vRNA load peaked in the lungs 2–4 and 2–7 dpi, respectively | Non-lethal | 63 |
| Mouse hACE2 (adenoviral vector) |
IN: 105 FFU IN or IV: 105 FFU 2019n-CoV/USA_WA1/2020 |
Lung pathology peaked 8 dpi Histopathology consistent with severe viral pneumonia found in patients with COVID-19 |
vRNA load peaked in the lungs 1–4 dpi and was detected in the heart, brain, liver, spleen, kidney, serum and gastrointestinal tract Infectious virus was detected in the lungs 4 dpi (∼106 PFU/g) |
Non-lethal | 64 |
| Mouse hACE2 (CRISPR–Cas9 knock-in) |
IN: 4 × 105 PFU BetaCoV/Wuhan/AMMS01/2020 |
Young and aged mice developed interstitial pneumonia 6 dpi |
No longitudinal viral load data available vRNA detected in the lungs, trachea and brain 6 dpi |
Non-lethal | 65 |
| Golden Syrian hamster |
IN: 8 × 104 TCID50 BetaCoV/Hong Kong/VM20001061/2020 |
Lung consolidation peaked 7 dpi Transmission from infected animals to naive animals via direct and indirect contact |
vRNA and infectious titre peaked in the lungs 2–5 and 2 dpi, respectively | Non-lethal | 28 |
| Syrian hamster |
IN: 105 PFU Hong Kong isolate |
Lung pathology and consolidation peaked 7 dpi Transmission from infected animals to naive animals in direct contact |
vRNA and infectious titre peaked in the lungs and nasal turbinate 2–4 dpi | Non-lethal | 29 |
| Syrian hamster |
IN or ocular: 103–105.3PFU SARS-CoV-2/UT-NCGM02/Human/2020/Tokyo |
Lung pathology peaked 6–8 dpi for low-dose and high-dose infected animals High-dose infected animals had higher severity scores (by CT scan) |
Infectious virus titre peaked in the lungs, nasal turbinate and brain 3 dpi | Non-lethal | 66 |
| Ferret |
IN: 105.5 TCID50 NMC-nCoV02 |
No longitudinal lung pathology data available Acute bronchiolitis 4 dpi Transmission from infected animals to naive animals in direct and indirect contact |
vRNA and infectious titre peaked in nasal turbinate and lungs 4 dpi | Non-lethal | 27 |
| Ferret |
IN or IT: 105 PFU SARS-CoV-2/CTan/human/2020/ Wuhan SARS-CoV2/F13/environment/ 2020/Wuhan |
No longitudinal lung pathology data available Severe lymphoplasmacytic perivasculitis and vasculitis in the lungs 13 dpi |
vRNA and infectious titre peaked in nasal wash 6 and 4 dpi, respectively vRNA and infectious virus were not detected in the lower respiratory tract |
Non-lethal | 67 |
| Rhesus macaque |
IT: 1 × 106 TCID50 SARS-CoV-2/WH-09/human/2020/CHN |
Mild-to-moderate interstitial infiltration in animals with pneumonia | vRNA load peaked in nasal swabs 3 dpi (106.5 RNA copies/ml) | Non-lethal | 68 |
| Rhesus macaque |
IN and IT: 1.1 × 104–1.1 × 106 PFU SARS-CoV-2 isolate USA-WA1/2020 |
Peak lung inflammation and pneumonia 2 dpi, diminished by 4 dpi | vRNA load peaked in nasal swabs and BAL 2 dpi | Non-lethal | 26 |
| Rhesus macaque |
IN, IT, ocular and oral: 2.6 × 106 TCID50 SARS-CoV-2 isolate USA-WA1/2020 |
Radiograph scores peaked 3–5 dpi |
vRNA load peaked in nasal swabs 1–3 dpi and BAL 1 dpi Infectious virus isolated in nasal swabs, BAL and throat swabs 1–3 dpi |
Non-lethal | 46 |
| Cynomolgus macaque |
IN and IT: 1 × 106 TCID50 BetaCoV/Munich/BavPat1/2020 |
Histopathological changes characteristic of acute and advanced diffuse alveolar damage 4 dpi | vRNA load peaked 2 dpi in young animals and 4 dpi in old animals | Non-lethal | 69 |
| Cynomolgus macaque |
IB: 3.65 × 106 PFU 2019-nCoV USA-WA1-A12/2020 |
Percent change in lung hyperdensity peaked 2–8 dpi CT lung scores peaked 2–6 dpi |
vRNA load peaked in nasal, rectal and oral swabs 2 dpi | Non-lethal | 70 |
| African green monkey |
Aerosol: 2–2.5 × 103 PFU IT, IN, oral and CJ: 3.61 × 106 PFU SARS-CoV-2 isolate USA-WA1/2020 |
2 of 4 animals (16 years) developed pneumonia, ARDS and a cytokine storm Animals euthanized 8 and 22 dpi owing to rapidly declining clinical condition |
vRNA load peaked in nasal and pharyngeal swabs 3–7 dpi | Lethal | 71 |
| African green monkey |
IT and IN: 5 × 105 PFU SARS-CoV-2/INMI1-Isolate/2020/Italy |
Thoracic radiographs inconclusive 2–5 dpi Necropsy of 3 animals 5 dpi showed varying degrees of pulmonary consolidation with hyperaemia and multifocal lesions with evidence of diffuse alveolar damage |
vRNA load peaked in nasal swabs 2–4 dpi and in BAL 3–5 dpi Infectious titre peaked in nasal swabs 2 dpi and in BAL 3–5 dpi vRNA and infectious titre peaked in oral swabs 3 dpi |
Non-lethal | 72 |
| African green monkey |
Aerosol: 103–104 PFU IN, IT, oral and ocular: 106 PFU SARS-CoV-2/München-1.1/2020/929 |
Peak lung inflammation and pathology (in PET or CT scan) 4 dpi, lesions resolved by 11 dpi |
vRNA load peaked in oral, nasal and conjunctival swabs 2–7 dpi Infectious virus isolated from oral, nasal, rectal and ocular swabs 2–4 dpi |
Non-lethal | 47 |
| Baboon |
IN, IT and ocular: 1.05 × 106 PFU SARS-CoV-2 isolate USA-WA1/2020 |
Bronchitis observed 14–17 dpi No longitudinal lung pathology data available |
vRNA load peaked in nasopharyngeal swabs and BAL 3 dpi | Non-lethal | 73 |
| Marmoset |
IN, IT and ocular: 1.05 × 106 PFU SARS-CoV-2 isolate USA-WA1/2020 |
Very mild pathology No longitudinal lung pathology data available |
vRNA load peaked in nasal wash samples 3 dpi | Non-lethal | 73 |
ARDS, acute respiratory distress syndrome; BAL, bronchoalveolar lavage; CJ, conjunctival; COVID-19, coronavirus disease 19; CT, computed tomography; dpi, days post inoculation; FFU, focus forming units; hACE2, human angiotensin-converting enzyme 2; IB, intrabronchial; IN, intranasal; IT, intratracheal; IV, intravenous; PET, positron emission tomography; PFU, plaque forming units; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TCID50, 50% tissue culture infectious dose; vRNA, viral RNA.