3.2 Hamster Model:
Golden Syrian hamsters are rodents that belong to the hamster subfamily and are widely used in research related to human diseases, accounting for 19% of research in the U.S (”The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents,” 2012). These hamsters showed productive viral replication as well as pathological signs in lungs and disease pathogenesis when challenged with SARS-CoV. However, despite the fact that lung pathology looked similar to that in humans, hamsters did not recapitulate clinical disease or mortality in SARS-CoV infection (Roberts et al., 2006). Many other studies used different strains Urbani, HKU-39849, Frankfurt 1, and a recombinant clone GD03T0013 but failed to recapitulate the SARS-CoV-2 mediated fatality in hamsters (Roberts et al., 2008). Collectively, these studies demonstrate that the hamster represents a suitable model for SARS-CoV infection but is not suitable to model severe disease that is at times fatal in the human.
Hamsters support SARS-CoV-2 infections (J. F. Chan et al., 2020) as shown recently. In a study from Hong Kong, 8 hamsters were infected with a viral isolate purified from the nasopharyngeal aspirate specimen of a laboratory-confirmed COVID-19 patient. Clinical signs included weight loss, ruffled furs, and stressed breathing with high viral loads in the hamster’s lungs and intestines. Histopathology examination revealed patches of inflammation and inflammatory cells with pleural invaginations in lung tissues (J. F. Chan et al., 2020) (Table 1) . Another study used hamsters as a model to understand the mechanism of intra-species transmission (Sia SF, 2020). In this study, nine hamsters were infected intranasally with BetaCoV/Hong Kong/VM20001061/2020 virus where peak viral load was attained at day 2 post-infection in nasal washes, lungs, and fecal samples. Histopathological changes like consolidation and infiltration in lungs, kidneys, and intestines were detectable 7 days post-infection. At 24 hours post-inoculation, 3 of the experimentally infected animals were group housed with 3 naïve hamsters and after remaining in full contact for one day; they successfully transmitted the infection to naïve hamsters with substantial viral loads in nasal swabs, and clinical signs including weight loss and breathing distress (Table 1) . At Day-13 post-contact, both donors and contact hamsters had developed neutralizing antibodies against SARS-CoV-2 (Sia SF, 2020). These studies clearly suggest that hamsters can be used to better understand the transmissibility of the virus.
The sequence of hamster ACE2 revealed the presence of asparagine (N) at position 82, which contrasts with human ACE2 that has lysine (K) at this position. Although hamsters were permissible for SARS-CoV and SARS-CoV-2 infections, they did not show severe fatal disease as seen in the human, which may be due to the amino acid change at position 82. Also, there is a lack of sequence data and other tools needed to carry out experiments in hamsters. Despite these shortcomings, hamsters may be used as models for SARS-CoV-2 transmission and consequently immunoprophylaxis studies because of their permissiveness to infection.