Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility

Abstract

Background A physiological small animal model that resembles COVID-19 with low mortality is lacking. Methods Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian hamster is an option. Virus challenge, contact transmission, and passive immunoprophylaxis were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titre, chemokine/cytokine assay, and neutralising antibody titre. Results The Syrian hamster could be consistently infected by SARS-CoV-2. Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with virus nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked cytokine activation were observed within the first week of virus challenge. The lung virus titre was between 105-107 TCID50/g. Challenged index hamsters consistently infected naïve contact hamsters housed within the same cage, resulting in similar pathology but not weight loss. All infected hamsters recovered and developed mean serum neutralising antibody titre ≥1:427 fourteen days post-challenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent non-synonymous adaptive mutation of the spike was found in viruses isolated from infected hamsters. Conclusions Besides satisfying the Koch’s postulates, this readily available hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.

ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study

“…This allowed the authors to predict that hamsters could be infected, which was experimentally confirmed -underlining the reliability of in silico modeling-and could be subsequently at the origin of inter-animal transmission. However, hamsters, although developing clinical signs of the infection and relative histopathological changes, did not die 50 : we speculate that lethality may be related to Spike/ACE2 affinity. On the other hand, the lower affinity in bat could explain -besides a better immune control-why these animals are carriers without dying.…”

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

“…Non-human primate models have proven to be highly valuable for other infectious diseases, but are expensive to maintain and numbers of experimental animals are limited. Our results provide an extended list of potential species that might be useful as animal models for SARS-CoV-2 infection and pathogenesis, including Chinese hamster and Syrian/Golden hamster (49) , and large animals maintained for biomedical and agricultural research (e.g., domesticated…”

“…Data on susceptibility of wild animals to SARS-CoV-2 is still very limited. It has been reported that a captive Malayan tiger was infected by SARS-CoV-2(9) and that domestic cats, ferrets(47) , rhesus macaques(48) and Syrian golden hamsters(49) are susceptible to experimental infection by SARS-CoV-2. These results agree with our predictions of ACE2 binding ability to SARS-CoV-2 S(Fig.…”

Comparison of SARS-CoV-2 infections among 3 species of non-human primates

“…Since December of 2019, scientists all over the world have been working to establish animal model of COVID-19. So far there are several models reported in preprinted journals or peer-reviewed published journals, including two small murine models (hACE2 transgenic mouse 14 and Gold Syrian hamster 15 ), one ferret model 16 Retrospective studies of clinical features of COVID-19 show that older patients have more severe diseases, which may be associated with comorbidities, including tumor, diabetes, obesity, hypertension, heart diseases and so on [18][19][20] . These underlying diseases may make senior patients more susceptible to SARS-CoV-2 infection and worsen COVID-19.…”