Table 1.

Animal models of SARS-CoV-2.

Sr. No	Animal species	Disease induction (strain and route)	Clinical signs	Advantages	Disadvantages	References
1	Rhesus macaques	SARS-CoV-2, 2.6 × 106 TCID50, IT or IN	Virus shedding in upper, lower respiratory tract and intestinal tract	Useful for pathogenesis, vaccines and therapies studies	Small sample size	Munster et al. (2020)
2	Rhesus macaques	3–5 years old and 15 years old, SARS-CoV-2, 1 × 106 TCID50, IT	Severe interstitial pneumonia and significantly viral replication in respiratory tract in old monkeys than young monkeys	Useful for pathogenesis, vaccines and therapies studies	Clinical signs were transient	Yu et al. (2020)
3	Rhesus macaques	SARS-CoV-2, 4.75 × 106 PFU, IT and IN	Increased body temperature, progressive pulmonary infiltration, high levels of viral genome RNA, showed progressively abnormal chest radiograph	Suitable for vaccines and therapeutics studies against SARS-CoV-2	Availability, housing cost	Lu et al. (2020)
4	Macaca fascicularis	SARS-CoV-2, 4.75 × 106 PFU, IT and IN	Progressive pulmonary infiltration, abnormal chest radiograph; swab samples collected on 2 dpi from M. fascicularis showed surprisingly high levels of viral genome	Mimic pathogenesis closer to clinical disease	Lower level of viral RNA, costly, limited size availability	Lu et al. (2020)
5	Common marmoset	SARS-CoV-2, 1.0 × 106 PFU, IT and IN	One-third of common marmoset had a slightly elevated body temperature, higher viral load in blood, lower levels of viral RNA were detected in swab samples from C. jacchus	–	Not showed severe histopathological changes in lung as pneumonia, relatively resistant to SARS-CoV-2 infection	Lu et al. (2020)
6	African green monkeys	SARS-CoV-2, 5.0 × 105 PFU, IT or IN	Pulmonary consolidation with hemorrhage, pronounced viral pneumonia, release of inflammatory mediators with similar immune signatures as human cases	Considered gold standard model for infectious pathogens	Did not develop overt, debilitating clinical illness; not easy to handle and costly	Woolsey et al. (2020)
7	Cynomolgus monkeys	SARS-CoV-2, 2 × 105 TCID50, IT or IN	Diffuse alveolar damage in lungs and viral titer in upper and lower respiratory tract	Viral titer remain for long period and histopathological changes in the lungs	No overt clinical signs	Rockx et al. (2020)
8	Transgenic hACE2 mice	SARS-CoV-2 (HB-01), 105 TCID50/50 μL, IN	Weight loss and increase in virus replication in the lung and interstitial pneumonia also macrophages accumulation alveolar cavities	Fulfilled Koch's postulates; helpful in development of therapeutics and vaccines	Short supply and high cost of hACE2-transgenic mice; mild inflammatory responses and lung damage	Bao et al. (2020)
9	BALB/c mice	SARS-CoV-2 (MACSp6), 7.2 × 105 PFU, IN	Infected all ages of mice; acute inflammatory responses closely related to the damage of lung tissues; levels of chemokines increased significantly in the aged mice as comparison to younger mice	Easy handling breeding, convenient, economical, and effectively used for evaluation of in vivo evaluation of vaccines and therapeutics	Exhibited moderate inflammatory responses	Gu et al. (2020)
10	BALB/c mice	10-week old and 12 month-old SARS-CoV-2 MA, 105 PFU, IN	Age-related increase in pathogenesis	Useful for pathogenesis, vaccine immunogenicity and therapeutic efficacy studies	–	Dinnon et al. (2020)
11	Transgenic hACE2 mice HFH4-hACE2 in C3B6 mice)	SARS-CoV-2, 3 × 104 TCID50 (for naïve infection) or 7 × 105 TCID50 (for the viral challenge), IN	Weight loss, interstitial pneumonia, lymphopenia, gender susceptibility, viral titer in eye, heart & brain apart from lungs	Partially simulated COVID-19 pathology	LD50 of the model is not determined; lethal encephalitis	Jiang et al. (2020)
12	hACE2 mice	SARS-CoV-2 4 × 105 PFU-IN, 4 × 106 PFU-IG	High viral titre in lung, brain and trachea; interstitial pneumonia; increase cytokines levels	Helpful in study of transmission, pathogenesis, evaluating of vaccines and therapeutic efficacy	-	Sun et al.2020b
13	Ad5-hACE2-transduced mice	SARS-CoV-2 1 × 105 PFU-IN	Weight loss, high virus titer in lungs, severe pulmonary pathology	Useful for the study of pathogenesis and testing for antiviral therapeutics and vaccines	Absence of critical condition and extra-pulmonary manifestations of infection	Sun et al.2020a
14	HACE2-transduced mice	SARS-CoV-2 1 × 105 FFU- IN & IV	Weight loss, high viral loads in lung, severe lung pathology	Helpful to study pathogenesis, vaccines and therapeutics	Mouse to mouse variation in expression of hACE2, tissue distribution and mild bronchial	Hassan et al.2020
15	Golden Syrian hamster	SARS-CoV-2, 105–107 TCID50, IN	Rapid breathing, loss of weight, diffuse alveolar damage and high lung viral load was observed	Readily available, physiological, and highly similarity with COVID-19 useful for study of pathogenesis, therapeutics and vaccines	There was a different outcomes in this study as comparison to previous study of SARS-CoV, not tested protein expression only tested mRNA of the hamsters cytokine profiles	Chan et al. (2020)
16	Golden Syrian hamster	SARS-CoV-2, Beta-CoV/Hong Kong/VM20001061/2020 virus, 8 × 104 TCID50, IN	Weight loss, significant viral replication, transmission of infection via aerosols	Useful for immunological studies for vaccine development	Rapid viral clearance on 7 dpi	Sia et al. (2020)
17	Ferrets	SARS-CoV-2, 105.5 TCID50, IN	Showed increased body temperatures and high virus titers in upper respiratory tracts	Viral infection and transmission	Low viral titer in lungs	Kim et al. (2020)

SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; IN, intranasal; IT, intratracheal; IG, intragastric; TCID₅₀, 50% Median Tissue Culture Infectious Dose; PFU, Plaque forming units; dpi, day post infection