Table 2.
Recommended Animal Models for Specific Stages of Human COVID-19 Disease
| COVID-19 Medical Need | Disease aspect | Recommended model(s) | Advantages | Limitations |
|---|---|---|---|---|
| Drugs and immunomodulators | Lung lesions, Interstitial pneumonia | Mouse models | Ease of handling; availability for statistical significance | May not be reflective of human pharmacokinetics; may not metabolize antiviral prodrugs as humans |
| Syrian Golden hamsters | Ease of handling; availability for statistical significance; historically used by coronavirus researchers due to natural ACE2 permissiveness & tissue distribution | May not be reflective of human pharmacokinetics; may not metabolize antiviral prodrugs as humans | ||
| AGMs, Aged AGMs | Immune modulators can be tested | Availability of animals | ||
| Rhesus macaque | Pharmacokinetics similar to humans | Limited supply to test drugs; narrow window for treatment | ||
| Cough, fever | Ferret | Symptoms seen in humans | Disease is mild | |
| Cytokine storm | Aged AGMs | Cytokine response well characterized; Immune modulators can be tested | Availability of aged animals | |
| K18-ACE2 mice | Cytokine response well characterized; Immune modulators can be tested | – | ||
| ARDS | Aged AGMs | Immune modulators can be tested | Availability of aged animals | |
| K18-ACE2 mice | Drugs could show promise; disease presentation resembles ARDS | Not true ARDS; Narrow treatment window | ||
| Coagulation | None to date | – | – | |
| Post-exposure prophylaxis with mAbs | Limit viremia | Rhesus or cynomolgus macaques | PK similar and valuable information about dosing; reagents available | Anti-drug antibody may develop |
| Mouse models | Potential for quick screens to choose cocktails | May not be reflective of human dosing or efficacy | ||
| Syrian Golden hamsters | Potential for quick screens to choose cocktails | May not be reflective of human dosing or efficacy | ||
| Vaccines designed to generate neutralizing antibodies | Limit viremia; Prevent infection; reduced pathology | Mouse, Syrian golden hamster | Proof of concept, required prior to NHP studies; multiple models are equivalent | – |
| Rhesus macaque, cynomolgus macaque | B cell responses similar to humans; can quantify correlates of protection; reagents available | Low level of viremia may be easier to clear than humans | ||
| Antibody-dependent enhancement | None to date | – | – | |
| Vaccines designed to generate T cell response | Limit viremia or peak of viremia; reduced pathology | Rhesus macaque, cynomolgus macaque | T cell responses similar to humans and can be studied in depth; identify correlates; reagents available | T cell ‘only’ vaccines unlikely to protect from infection but can test concept |
Within each medical need, the disease aspects are presented in order of increasing complexity, while animal models are presented in the order in which they should be approached. Advantages and limitations are also presented to help in the selection of the appropriate animal model. AGM, African green monkey; ARDS, acute respiratory distress syndrome; mAbs, monoclonal antibodies; NHP, non-human primates; PK, pharmacokinetics