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pathologie@vetmed.fu-berlin.de
Early in the dramatic global pandemic of the coronavirus disease 2019 (COVID-19) a suitable animal model was highly needed that would facilitate the development and testing of therapeutic approaches and vaccines. In contrast to other small rodents, hamsters were soon found to be naturally susceptible to the causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Syrian hamster (Mesocricetus auratus) has since been used by many groups as a popular model. It recapitulates several typical features of COVID-19 as seen in patients with a mild, self-limiting course, including specific patterns of respiratory tract inflammation, vascular endothelialitis, age dependence of lesions and full recovery with protective seroconversion. However, it seemingly does not allow to model other specific aspects of the disease including certain immunopathologies as seen in highly susceptible human patients, which are of strongest clinical concern. For this purpose and group of patients, the Roborovski dwarf hamster (Phodopus roborovskii) appears to be a much more suitable model species after infection with SARS-CoV-2. On the other hand, the Chinese hamster and the two dwarf hamster species Roborovski dwarf hamster and Campbell's dwarf hamster showed similar or even milder courses when compared to the Syrian hamster and thus appeared less suitable as models. Still, it will be interesting to explore the genetic and immuno-mechanistic backgrounds of the different susceptibilities of the five closely related hamster species.
Unfortunately, only limited diagnostic tools, including antibodies for immunohistochemistry, and information on immune functions and molecular pathways are available for hamsters when compared to mice. This still somewhat limits mechanistic studies and inference of data derived from hamsters to patients in several aspects. The limitation can, however, be largely overcome by the current technical developments and availabilities of genomic, transcriptomic and proteomic information from SARS-CoV-2 infected hamsters and human patients, allowing for detailed molecular and mechanistic comparisons. As in other animal models, the strengths and weaknesses of hamster models of COVID-19 rest upon a solid understanding of their similarities to and differences from the human disease in terms of their being “fit-for-purpose”, which will be reviewed in this presentation.
Finally, as COVID-19 will not be the last pandemic requiring urgent establishments of suitable preclinical models, it is imperative to learn from our hamster experiences and to recapitulate our insights gained from these models, including aspects of quality management and reporting standards for experimental animal studies.
Suggested literature:
Gruber AD, Osterrieder N, Bertzbach LD, et al. Standardization of reporting criteria for lung pathology in SARS-CoV-2 infected hamsters – What matters? Am J Resp Cell Mol Biol. 2020;63:856-859.
Nouailles G, Wyler E, Pennitz P, et al. Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19. Nat Commun. 2021;Online Ahead of Print.
Trimpert J, Vladimirova D, Dietert K, et al. The Roborovski dwarf hamster – A highly susceptible model for a rapid and fatal course of SARS-CoV-2 infection. Cell Rep. 2020;33:108488.