Table 1:
Experimental infection of SARS-CoV-2 in animals.
| Animals | SARS-CoV-2 strain | Dose | Inoculation route | Symptoms | Findings | References |
|---|---|---|---|---|---|---|
| HFH4-hACE2 C3B6 mice | SARS-CoV-2 (IVCAS 6.7512) |
Primary infection: 3 × 104 TCID50 Challenge: 7 × 105 TCID50 |
Intranasal | No visible clinical signs up to 3 DPI; respiratory distress and recovery; some show rapid weight loss | Interstitial pneumonia; virus replication in lungs, brain. Some animals showed death with neurological symptoms. Pre-exposure to virus protects mice from high-dose virus challenge | 32 |
| Mice expressing hACE2 by CRISPR/Cas9 knock-in | SARS-CoV-2 strain (BetaCoV/Wuhan/AMMS01/2020) | 4 × 105 PFU | Intranasal | Interstitial pneumonia | Virus replication in lungs trachea and brain. Intragastric route led to respiratory tract infection | 33 |
| 4 × 106 PFU | Intragastric | – | ||||
| Transgenic mice expressing hACE2 | SARS-CoV-2 strain HB-01 | 105 TCID50 | Intranasal | Weight loss | Virus replication in lungs. interstitial pneumonia and infiltration of macrophages and lymphocytes | 28 |
| Mice (BALB/c) | SARS-CoV-2 MA10 (SARS-CoV-2 MA passaged ten times in mice to obtain) | 102,103,104 and 105 PFU | Intranasal | Dose-dependent increase in morbidity and mortality | Mortality rates of 20% for 104 PFU dose and 60% for 105 PFU dose | 27 |
| Mice (BALB/c) | SARS-CoV-2 MA (Recombinant SARS-CoV-2 with designed spike for mouse adaptation) | 105 PFU | Intranasal | Mild to moderate disease | Virus replication high in lung tissue on 2 DPI but was cleared by 4 DPI | 29 |
| Mice transduced with adeno-associated virus 9 encoding hACE2 (5 × 109 genomic copies/ animal, intratracheal) | SARS-CoV-2 isolate USA-WA1/2020 | 106 PFU | Intranasal | – | No significant difference between viral RNA or viral titre between IFN-α receptor–deficient B6/J mice, IFN regulatory factor 3/7 double knockout B6/J, and wild type B6/J AAV-hACE2–infected mice. Antibody response observed between 4 and 7 DPI which increased till 14 DPI | 36 |
| BALB/c Mice transduced with adenovirus 5 expressing hACE2 (2.5 × 108 PFU/animal, intranasally) | SARS-CoV-2 strain 2019 n-CoV/USA_WA1/2020 | 105 Focus Forming Unit | Intranasal or Intranasal and intravenous | Weight loss | High level of viral RNA detected in lung. Viral RNA not detected in kidney, gastrointestinal tract tissues, or in serum | 35 |
| Mice (HFH4-hACE2) | SARS-CoV-2 | 105 PFU | Intranasal | – | 40% of infected mice died. Virus detected in lungs on 2 and 5 DPI. It was also detected in brain on 5 DPI | 29 |
| Mice (K18-hACE2 mice) | SARS-CoV-2 (strain 2019n-CoV/USA_WA1/2020) | 2.5 × 104 PFU | Intranasal | Weight loss | Highly susceptible, succumb to disease by 7 DPI. High levels of virus and viral RNA detected in the lungs | 31 |
| Mice (HFH4-hACE2) | Recombinant SARS-CoV-2 virus with D614G mutation in spike derived from WA1 strain | 103 PFU | Intranasal | Minimum body weight loss | High viral titres in lungs and brain tissue. Similar susceptibility to wild-type and D614G variant | 30 |
| Syrian Hamster | SARS-CoV-2 isolated from Honk Kong patient | 105 PFU | Intranasal | Weight loss, rapid breathing | Animal-to-animal transmission demonstrated through direct contact. On 14 DPI, all infected hamsters had neutralizing antibody titres ≥ 1:427 | 37 |
| Syrian Hamster | SARS-CoV-2/UT-NCGM02/Human/2020/Tokyo and SARS-CoV-2/UW-001/Human/2020/Wisconsin | 105.6 or 103 PFU | Intranasal and intraocular | Weight loss | High susceptibility | 38 |
| Syrian Hamster | Recombinant SARS-CoV-2 virus with D614G mutation in spike derived from WA1 strain | 103 PFU | Intranasal | Weight loss | High susceptibility for D614G variant with significantly faster spread between hamsters through aerosol and droplets | 30 |
| Mink | SARS-CoV-2/HRB25/human/2020/CHN (HRB25, GISAID access no. EPI_ISL_467430) | 5 × 106 PFU | Intranasal | Weight loss between 10 and 20% at around 8 DPI; 5% in in-contact animals | Highly susceptible. Upper and lower respiratory tract infection. Viral RNA and infectious virus detected in most of the respiratory tract samples, with severe lung pathology. Virus transmission through droplet observed | 39 |
| Ferrets | SARS-CoV-2/F13/environment/2020/Wuhan or SARS-CoV-2/CTan/human/2020/Wuhan | 105 PFU | Intranasal | Fever and loss of appetite | Viral RNA and infectious virus detected in the nasal turbinate, soft palate, and tonsils of infected ferrets. Virus replication in upper respiratory tract up to 8 days without causing severe disease or death | 40 |
| Ferrets | SARS-CoV-2 isolate from South Korea (NMC-nCoV02) | 105.5 TCID50 | Intranasal | Fever, acute bronchiolitis | Highest infectious virus and viral RNA detected in nasal washes of infected ferrets on 4 DPI. Virus also shed in saliva, urine and faeces. Viral RNA detected in nasal washes and faeces of contact animals. Ferret-to-ferret transmission detected | 41 |
| Ferrets | SARS-CoV-2 (isolate BetaCoV/Munich/BavPat1/2020) | 6 × 105 TCID50 | Intranasal | Not defined | Ferret-to-ferret transmission demonstrated through direct contact and indirect contact through respiratory droplets. Infectious titre ranged between 0.75 and 2.75 log10 TCID50/ml in the donor ferrets, from 0.75 to 3.5 log10 TCID50/ml in the direct contact ferrets from 0.75 to 4.25 log10 TCID50/ml in the indirect contact ferrets. Infected ferrets in all groups seroconverted by 21 DPI or exposure | 42 |
| Cats | SARS-CoV-2 isolate UT-NCGM02/Human/2020/Tokyo | 5.2 × 105 PFU | Combination of intranasal, intratracheal, oral and ocular | – | Virus detected in all inoculated cats by 3 DPI. Virus detected in co-housed animals by 5 DPI | 44 |
| Cats | SARS-CoV-2/CTan/human/2020/Wuhan | 105 PFU | Intranasal | – | Viral RNA detected in nasal turbinates, soft palates, tonsils, trachea, or small intestine. Viral RNA not detected in lungs. Virus detected in the upper respiratory tract, tonsils, tracheas, and lungs but not in the small intestines. Younger cats more susceptible than older cats. Cat-to-cat transmission detected | 40 |
| Cats | SARS-CoV-2 virus strain WA1/2020WY96 | 3 X 105 PFU | Intranasal | No clinical signs | Virus shed up to 5 DPI. Contact cat shed virus up to 7 DPI. Seroconversion by 7 DPI. Neutralizing antibody titres ≥ 1:2560 by 14 DPI. Virus shedding not detected in challenged cats | 45 |
| Rhesus macaques | SARS-CoV-2 isolate nCoV-WA1–2020 | 2 × 105 TCID50 | Intranasal | Initial weight loss, irregular respiratory pattern and piloerection, reduced appetite, hunched posture, pale appearance, dehydration | High susceptibility. Virus shedding highest in nose, throat and bronchioalveolar lavage (BAL). Virus isolated from nose and BAL on 1 and 3 DPI. Pulmonary infiltrates visible in lung radiographs | 106 |
| 4 × 105 TCID50 | Oral | |||||
| 16 × 105 TCID50 | Intratracheal | |||||
| 2 × 105 TCID50 | Ocular | |||||
| Rhesus macaques | SARS-CoV-2/WH-09/human/2020/CHN |
Primary infection on day 0: 106 TCID50/mL Reinfection on day 28: 106 TCID50/mL |
Intratracheal | Interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts | Initial infection with SARS-CoV-2 protects against reinfection during early recovery phase. Reinfection increased neutralizing antibodies | 107 |
| Rhesus macaques | SARS-CoV-2 USA-WA1/2020 |
Primary infection: 1.1 × 104 or 1.1 × 105 or 1.1 × 106 PFU Reinfection on 35 days: doses same as primary infection |
Intranasal and Intratracheal | Interstitial pneumonia | High viral loads in the upper and lower respiratory tract. Primary infection with SARS-CoV-2 protects against rechallenge on 35 DPI. Up on reinfection, median viral load reduced by 5 log10 in BAL and nasal mucosa | 108 |
| Rhesus macaques | SARS-CoV-2 USA-WA1/2020 | 1.05 × 106 PFU | Ocular, intratracheal and intranasal | Acute respiratory distress. Mild-to-moderate pneumonia | Old and young age groups recover in two weeks. T cell memory and bystander cytokine production. Lower titres of specific IgG antibodies in old animals | 49 |
| Cynomolgus macaques | SARS-CoV-2 (isolate BetaCoV/Munich/BavPat1/2020) | 106 TCID50 | Intranasal and Intratracheal | No clinical sign | Virus shedding from nose and throat. SARS-CoV-2 antigen detected in type I and II pneumocytes in affected lung and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae | 50 |
| Baboons | SARS-CoV-2 USA-WA1/2020 | 1.05 × 106 PFU | Ocular, intratracheal and intranasal | Acute respiratory distress, severe pneumonia | Infectious virus detected on 3 DPI. Highest viral load in rectal swab | 49 |
| Marmosets | SARS-CoV-2 USA-WA1/2020 | 1.05 × 106 PFU | Ocular, intratracheal and intranasal | Mild infection | Viral RNA peaked at 3 DPI | 49 |
| White-tailed deer | SARS-CoV-2 TGR/NY/20 (isolated from infected tiger) | 5 × 106.3 TCID50 | Intranasal | Subclinical infection | Virus shedding detected in nasal secretions from all inoculated and contact animals | 51 |
| White-tailed deer | SARS-CoV-2/human/USA/WA1/2020 lineage A | 2 ml dose of 1 × 106 TCID50 per animal (1:1 titre ratio of both viruses) | Intranasal and oral | Subclinical infection | Virus shedding through nasal and oral secretions of infected animals and contact animals. B.1.1.7 isolate sequence more than the lineage A WA1 isolate sequence. Virus transmission through direct contact and vertically from doe to foetus | 52 |
| SARS-CoV-2/human/USA/CA_CDC_5574/2020 lineage B.1.1.7 VOC | ||||||
| Sheep | SARS-CoV-2/human/USA/WA1/2020 lineage A | 2 ml dose of 1 × 106 TCID50 per animal (1:10 titre ratio of lineage A: lineage B) | Intranasal and oral | Mild infection | Oral and nasal swab positive on 1 DPI. Viral RNA detected in respiratory tract and lymphoid tissues at 4 and 8 DPI. Virus transmission to naïve animals were limited | 53 |
| SARS-CoV-2/human/USA/CA_CDC_5574/2020 lineage B.1.1.7 | ||||||
| Dogs | SARS-CoV-2 virus strain WA1/2020WY96 | 1.4 × 105 PFU | Intranasal | No clinical signs | Virus shedding not detected. Neutralizing antibody titres between 1:40 and 1:80 at 14 to 21 DPI | 45 |
| Dogs | SARS-CoV-2/CTan/human/2020/Wuhan | 105 PFU | Intranasal | No clinical signs | Low susceptibility. 2 out of 4 dogs seroconverted. Dog-to-dog transmission not detected | 40 |
| Racoon dogs | SARS-CoV-2 2019_nCoV Muc-IMB-1 | 105 TCID50 | Intranasal | No clinical signs | Virus detected in nasal and oropharyngeal swab samples on days 2–4. 66.6% of the contact animals infected | 43 |
| Cattle | SARS-CoV-2 strain Muc-IMB-1 | 105 TCID50 | Intranasal | No clinical signs | Virus replication and seroconversion in 2 or 6 animals. Cattle-to-cattle transmission not detected | 47 |
| Tree shrews | SARS-CoV-2 (strain not defined) | 106 PFU | Intranasal | Fever in young and old than adult animals | Low susceptibility. Highest viral load in pancreas in one animal | 48 |
| Bank voles | SARS-CoV-2 strain Muc-IMB-1 | 105 TCID50 | Intranasal | No clinical signs | Seroconversion within 8 days and viral RNA detected in nasal tissue for up to 21 days. Transmission to contact animals not detected | 46 |
| Pigs, chickens and ducks | SARS-CoV-2/CTan/human/2020/Wuhan | 105 PFU | Intranasal | No clinical signs | Not susceptible | 40 |
DPI days post-infection, PFU plaque-forming units, TCID50 50% tissue culture infective dose