Table 1.
Overview of preclinical models of SARS‐CoV‐2
| Virus | Dose, Route | Host strain | Host age | Clinical features | Survival | Reported duration of viral pneumonia | Ref. |
|---|---|---|---|---|---|---|---|
| MHV‐A59 | 5 × 104 PFU, i.n. | C57Bl/6 | 6‐9 weeks | Acute neuroinflammation | 100% survival | n.d. | [37] |
| 1.5 × 104–5 PFU, i.n. | C57Bl/6 | 4 weeks | Acute pneumonia | 97% survival | <11 days (infectious viral particles) | [48] | |
| 5 × 103 PFU, i.n. | A/J | 6‐8 weeks | Acute pneumonia | 20% survival by day 10 | 7 days (infectious viral particles) | [8] | |
| 7 × 102 – 3 PFU, i.n. | C57Bl/6 | 20‐24 months | Pneumonia, weight loss, reduced O2 saturation, and elevated serum proinflammatory cytokines in older mice. | 0% survival in old mice by day 7 | n.d. | [49] | |
| Mouse‐adapted SARS‐CoV‐2 1 | 1.6 × 104 PFU, i.n. | BALB/c | 6 weeks (young), 9 months (old) | Acute pneumonia in young mice, accompanying lung pathology in older mice. No clinical symptoms or weight loss | 60% survival | <4 days (infectious viral particles) | [59] |
| Mouse‐adapted SARS‐CoV‐2 2 | 105 PFU, i.n. | BALB/c | 12 weeks (young), 12 months (old) | Acute pneumonia in young mice, accompanying lung pathology in older mice. Weight loss and impaired viral clearance in older mice. | 100% survival | 7 days (viral RNA) | [60] |
| SARS‐CoV‐2 | 3 × 104 PFU, i.n. | hACE2 transgenic (HFH4 promoter) C3H and C57Bl/6 | 8‐10 weeks | Interstitial pneumonia, lymphopenia in mice with severe disease | 33‐50% survival by day 7 | 7 days (viral RNA) | [54] |
| 105 PFU, i.n. | hACE2 transgenic (mACE2 promoter) ICR | 6‐11 months | Lung pathology, weight loss, and viral titres in lungs | 100% survival | 7 days (viral RNA) | [58] | |
| 4 × 105 PFU, i.n. |
hACE2 (CRISPR/Casp9) C57Bl/6 |
4.5 weeks (young) 30 weeks (old) | Interstitial pneumonia and elevated cytokines in old mice, no clinical symptoms of weight loss in young mice | 100% survival | 6 days (viral RNA) | [56] | |
| 105 PFU, i.n./i.v. | AdV/hACE2 BALB/c | 8‐10 weeks | Lung pathology, weight loss and viral titres in lungs | 100% survival | 10 days (viral RNA) | [55] | |
| 105 PFU, i.n. | Ad5‐hACE2 BALB/c and C57Bl/6 | 6‐8 weeks | Lung pathology, weight loss and viral titres in lungs | 100% survival | 5 days C57Bl/6 6 days BALB/c (infectious viral particles) | [57] |
Ad5, Adenovirus type 5; AdV, Adenovirus; HFH4, hepatocyte nuclear factor 3/forkhead homologue 4; i.n., intranasal; i.v., intravenous; n.d., not determined.
1Six passages in BALB/c mice (MASCp6).
2 Spike Q498T/P499Y mutant binds mACE‐2.