From: Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review
Species (ref) | Number age (gender) | Virus strain dose* (inoculation route)† | Clinical signs & observation duration (DPI) § | Viral replication‡ (DPI) | Pathology & sacrificing date (DPI) | Immune response | Seroconversion (DPI) | Outcome Measures |
---|---|---|---|---|---|---|---|---|
Mice | WT-BALB/c, n = 3 | 2 × 105 TCID50 of P 4†† or 2 × 106 of P 6†† (IN) | NA | Lung (3) | Mild lung pathology (2) | Mild inflammatory response | NA | Interferon response to SARS-CoV-2 infection |
BALB/c: | SCID, n = 3 | (14) | No difference in viral load WT vs. SCID | No difference in lung pathology WT vs. SCID (2, 4, 7, 14) | ||||
WT¶ | ||||||||
SCID|| | 6–8 weeks (F) | |||||||
C57BL/6: | C57BL/6 n = 5 | 2 × 105 TCID50 of P 4 or 2 × 106 of P 6 (IN) | NA (14) | Lung (3) | Greater intra-alveolar hemorrhage and peribronchiolar inflammation in IFNar1−/− mice than WT and IL28r−/− mice (3) | Higher inflammatory response in IFNar1−/− vs. WT and IL28r−/− mice | NA | |
WT | IFNar1−/−¶¶ n = 14 | |||||||
Ifnar1−/− | Higher viral replication in IFNar1−/− mice vs. WT and IL28r−/− mice | (2, 4, 7, 14) | ||||||
Il28r−/− | 6–8 weeks (F) | |||||||
Boudewijns et al. (2020) [56] | C57BL/6, n = 5 | 2 × 105 TCID50 of P 4 or 2 × 106 of P 6 (IN) | NA (14) | Lung (3) | Mild lung pathology (3) | Mild inflammatory response | NA | |
IL28r−/−, n = 5 | No difference in viral load between WT and IL28r−/− | (2, 4, 7, 14) | ||||||
6–8 weeks (F) | ||||||||
Mice | hACE2 mice | SARS-CoV-2 (BetaCoV/Wuhan/IVDC-HB-01/2020|EPI_ISL_402119) | Slight | Highest viral load | Moderate interstitial pneumonia | MAC2, CD3+ T and CD19+ B cells in alveolar septum | IgG antibody response against SARS-CoV-2 (21) | Pathogenesis of COVID-19 |
hACE2‖‖ transgenic mice | (ACE2-HB-01) | Bristles | In lung (3) | Thickened alveolar septa | ||||
Weight loss | Intestine (1) | |||||||
n = 19 | 105 TCID50 (IN) | Arched back (14) | Alveolar macrophage, and alveolar epithelia (3) | Lymphocytes, macrophages, and monocytes infiltrates in the interstitial and alveolar space | ||||
6–11 months (M/F) | ||||||||
Bronchioles degeneration (3) | ||||||||
No pathology in intestine, spleen, heart, liver, kidney, brain, and testis | ||||||||
(1, 3, 5, 7) | ||||||||
Bao et al. (2020) [50] | WT-HB-01 (n = 15) | SARS-CoV-2 (BetaCoV/Wuhan/IVDC-HB-01/2020|EPI_ISL_402119) 105 TCID50 (IN) | No (14) | No viral RNA detectable in lung or intestine (1) | No (1, 3, 5, 7) | No | No | |
6–11 months (M/F) | ||||||||
Mock-treated hACE2 mice (n = 15) | PBS 50 μl (IN) | No (14) | No viral RNA detectable in lung or intestine | No (1, 3, 5, 7) | No | No | ||
6–11 months (M/F) | ||||||||
Mice | n = 5 6–8 weeks (M) | SARS-CoV-2 (BetaCoV/Hong Kong/VM20001061/2020 [KH1]) | NA | NA | NA | NA | IgG antibody response against SARS-CoV and SARS-CoV-2 spike protein and RBD | Cross-reactivity of antibodies against SARS-CoV and SARS-CoV-2 |
Infection | SARS-CoV (HK39849, SCoV) | |||||||
105 PFU (IN) | ||||||||
BALB/c: | n = 5 | Immunization with heat-inactivated plasma from SARS-CoV and SARS-CoV-2 (IP) | NA | NA | NA | NA | Cross-reactive antibody binding responses SARS-CoV-2 and SARS-CoV No cross-neutralization SARS-CoV-2 and SARS-CoV | |
WT | 6–8 weeks (M) | |||||||
Lv et al. (2020) [53] | Immunization | |||||||
n = 6 | Vehicle (IN) | NA | NA | NA | NA | |||
6–8 weeks (M) control | ||||||||
Transgenic mice | n = 7 | SARS1/SARS2-RdRp §§ | Improvement of pulmonary function | reduced lung viral load 102 PFU/lobe (5) | Decreased lung hemorrhage (5) (5) | NA | NA | Antiviral therapy testing |
C57BL/6***: | 17 weeks (F) | 103 PFU (IN) | (5) | |||||
Ces1c−/− | Remdesivir given at 1dpi | |||||||
Pruijssers et al. (2020) [55] | Remdesivir | |||||||
n = 7 | SARS1/SARS2-RdRp | Reduced pulmonary function by WPH††† (5) | Lung viral load | Lung hemorrhage (5) (5) | NA | NA | ||
17 weeks (F) | 103 PFU (IN) | 105 PFU/lobe (5) | ||||||
Control | Vehicle | |||||||
n = 3 | Mouse-adapted SARS-CoV-2 (BetaCoV/Wuhan/AMMS01/2020) | Weight loss old mice (5) (7) | Trachea, lung, heart, liver, and intestine, pneumocytes Type II | Thickened alveolar septa | Increased TNF-α, IL-1β, IL-6, and IL-5, MCP-1, G-CSF, and GM-CSF (3) | NA | Establishment of mouse-adapted SARSCoV-2 model of COVID19 | |
Young, 6 weeks (F) | Alveolar damage and focal exudation | |||||||
Hemorrhage, | ||||||||
n = 3 | 7.2 × 105 PFU (IN) | Viral replication similar in old vs. young cells (3) | Inflammatory cell infiltration | Higher and sustained cytokines levels in aged mice vs. young | ||||
Denaturation of endothelial tissues (3) | ||||||||
Mice | Old, 9 months (F) | Lung pathology similar in old vs. young mice (3, 5, 7) | ||||||
BALB/c: | ||||||||
WT | Control mice | NA | No weight loss | No viral protein | NO | NO | Evaluation of candidates vaccine | |
Gu et al. (2020) [54] | NA | |||||||
n = 10 | Immunization day 1, 14 | NA | No viral replication detectable in lungs (5) | No | NA | Higher IgG antibody response against SARS-CoV-2 (14) | ||
6–8 weeks | Challenged with mouse adapted SARS-CoV-2 | |||||||
Immunized with SARS-CoV-2 RBD-Fc protein | (IN), 4 weeks after second immunization | |||||||
PBS control with aluminum adjuvant | High viral load in the trachea and lungs (5) | Focal perivascular and peribronchiolar inflammation Thickened alveolar septa | NA | NA | ||||
Mice | n = 5 | SARS-CoV-2 | No (2) | No viral replication detectable in lung (2) | NA | NA | IgG1 ab1 protects hACE2 transgenic mice from SARS-CoV-2 infection. (2) | Evaluation of prophylaxis with monoclonal antibody |
6–9 weeks (F) | 105 PFU (IN) | |||||||
C3B6: hACE2 mice | ||||||||
Immunization | Human monoclonal IgG1 antibody (12 h) | |||||||
C3B6: | Prior the virus challenges (IP) | |||||||
hACE2 transgenic mice | n = 6 | SARS-CoV-2 | No (2) | Viral replication 103 PFU per lung (2) | NA | NA | No | |
6–9 weeks (F) | 105 PFU (IN) | |||||||
C3B6: hACE2 mice | ||||||||
BALB/c mice | Control | IgG1 m336 (no activity in vitro) | ||||||
Li et al. (2020) [51] | Balb/c, n = 5 | Mouse ACE2 adapted SARS-CoV-2‡‡ | No (2) | No viral replication detectable in lung lobe at different dosages (2) | NA | NA | IgG1 ab1 protected mice SARS-CoV-2 challenge (2) | |
10–12 months (F) | ||||||||
105 PFU (IN) | ||||||||
Human monoclonal IgG1 ab1 antibody (12 h) | ||||||||
Prior the virus challenges (IP) | ||||||||
Mice | hACE2 mice | SARS-CoV-2 | Weight loss | Lung (2), brain (5) | NA (2, 5) | NA | NA | Evaluation of vaccine and therapy in mouse-adapted SARS-CoV-2 model |
BALB/c: And hACE2 | NA | 105 PFU (IN) | Mortality 40% (5) (5) | |||||
Transgenic mice | BALB/c mice | SARS-CoV-2MA§ | Pulmonary obstruction (WBP)††† | Upper airway | NA | NA | ||
Dinnon et al. (2020) [52] | n = 33 | 105 PFU (IN) | Lung (2,4) | Greater lung inflammation and hemorrhage in old vs. young mice (2,4) | ||||
Young 12 weeks | ||||||||
BALB/c mice | Greater | Higher replication in old vs. young mice | ||||||
n = 34 | Weight and pulmonary | |||||||
12 months | Function loss in old vs. young mice | |||||||
Vaccination | SARS-CoV-2 spike (S) or nucleocapsid (N) | NA | Vaccine with spike S reduced lung and nasal turbinate titer (2) | NA | NA | NA | ||
n = 8–10 | ||||||||
10 weeks | Challenged 4 weeks post-inoculation with SARS-CoV-2 MA | |||||||
BALB/c | 105 PFU (IN) | |||||||
Prophylaxis | Subcutaneous administration interferon (IFN) lambda-1a 2 μg | Reduced SARS-CoV-2 MA replication in the lung (2) | NA | NA | NA | |||
Therapy | 18 h prior or 12 h after | |||||||
BALB/c | SARS-CoV-2 MA | |||||||
12 weeks | 105 PFU (IN) | |||||||
n = NA |