Preprint Review Version 1 This version is not peer-reviewed

Animal Models of SARS-CoV-2: A Systematic Review

Version 1 : Received: 3 July 2020 / Approved: 5 July 2020 / Online: 5 July 2020 (15:07:53 CEST)

How to cite: Goel, P.; Jain, V.; Dhua, A.K.; Yadav, D.K.; Verma, A.; Mitra, A.; Khanna, T.; Agarwala, S.; Bajpai, M. Animal Models of SARS-CoV-2: A Systematic Review. Preprints 2020, 2020070079 (doi: 10.20944/preprints202007.0079.v1). Goel, P.; Jain, V.; Dhua, A.K.; Yadav, D.K.; Verma, A.; Mitra, A.; Khanna, T.; Agarwala, S.; Bajpai, M. Animal Models of SARS-CoV-2: A Systematic Review. Preprints 2020, 2020070079 (doi: 10.20944/preprints202007.0079.v1).

Abstract

Background: The use of animal models for biomedical research provides us with a convenient and feasible route to establish causal relationships by recapitulating the temporal sequence of events in a controlled environment with a potential to manipulate the variables at multiple levels including genetic, protein, physiological or environmental. Objectives: The current review was conducted to gain insights into various animal models for the SARS-CoV-2 virus. Material and Methods: A literature review (PUBMED, PUBMED Central, PMC, Google Scholar, Google search engine) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in early April 2020 revealed 9 articles of interest. Search terms included covid 19, covid-19, novel corona virus, SARS-CoV-2, animal models, experimental models, laboratory models & covid 19 animal models. Two independent reviewers extracted the data; the third reviewer was involved in case of discrepancy. Results: SARS-CoV-2 shares an identical receptor binding domain with the SARS-CoV virus and has a superior binding affinity to the host ACE2. Based on this, the role of rhesus macaques, golden Syrian hamsters, transgenic hACE2 mice and ferrets as animal models have been studied. All four animals are susceptible to infection with SARS-CoV-2 with variable clinical presentation but universal recovery. The respiratory tract is primarily involved in all four models. Involvement of intestines was also seen in at least one study in each animal. Transfer to naïve animals in close contact has been documented in case of hamsters and ferrets. Seroconversion was documented in all although the role of convalescent sera was tested in hamsters only, with positive results though. Air-borne transmission was documented in ferrets and the possibility of feco-oral transmission was suggested for hamsters. The possibilities of recurrence and re-infection were ruled out by experiments upon the rhesus macaques. The fulfilment of Koch’s postulates has been highlighted. Discussion: The various studies available on animal models have been able to establish models of infection and transmission that recapitulate different aspects of disease in humans. However, the response between different animals and the same animal in different experiments is not completely coherent. Some of them do not manifest the disease clinically while others behave differently at molecular and immunological levels. Moreover, the physiology of these animals is not identical to human beings and the findings may not be extrapolated to human beings in an ‘as-is’ manner. Conclusions: The review acknowledges the achievements made by these experiments in a short span of time and highlighted the urgent need for a deeper dive in search of a quintessential animal model which can be studied for efficacy and safety of newer drugs and vaccines before a make-shift from the petri-dish to the human body can be contemplated.

Subject Areas

animal models; experimental models; SARS-CoV-2; COVID-19; rhesus macaque; monkey; hamster; ferrets; transgenic mice

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