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Review
. 2020 Nov;177(21):4851-4865.
doi: 10.1111/bph.15143. Epub 2020 Jul 19.

Animal models of mechanisms of SARS-CoV-2 infection and COVID-19 pathology

Simon J Cleary  1 , Simon C Pitchford  2 , Richard T Amison  2 , Robert Carrington  2   3 , C Lorena Robaina Cabrera  2 , Mélia Magnen  1 , Mark R Looney  1 , Elaine Gray  2   4 , Clive P Page  2
Affiliations
Review

Animal models of mechanisms of SARS-CoV-2 infection and COVID-19 pathology

Simon J Cleary et al. Br J Pharmacol. 2020 Nov.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 infections has led to a substantial unmet need for treatments, many of which will require testing in appropriate animal models of this disease. Vaccine trials are already underway, but there remains an urgent need to find other therapeutic approaches to either target SARS-CoV-2 or the complications arising from viral infection, particularly the dysregulated immune response and systemic complications which have been associated with progression to severe COVID-19. At the time of writing, in vivo studies of SARS-CoV-2 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2). These infection models have already been useful for studies of transmission and immunity, but to date only partly model the mechanisms involved in human severe COVID-19. There is therefore an urgent need for development of animal models for improved evaluation of efficacy of drugs identified as having potential in the treatment of severe COVID-19. These models need to reproduce the key mechanisms of COVID-19 severe acute respiratory distress syndrome and the immunopathology and systemic sequelae associated with this disease. Here, we review the current models of SARS-CoV-2 infection and COVID-19-related disease mechanisms and suggest ways in which animal models can be adapted to increase their usefulness in research into COVID-19 pathogenesis and for assessing potential treatments. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Model of factors driving progression to mild or severe COVID‐19. Flow diagram representing a model of protective versus dysregulated responses to SARS‐CoV‐2 infection. Most reported animal models of SARS‐CoV‐2 infection are likely to involve protective immunity and resolving pathology. Risk factors and mechanisms implicated in driving severe responses to SARS‐CoV‐2 infection provide insights into how to push models towards replicating pathological responses. Adapted from Channappanavar and Perlman (2017)
FIGURE 2
FIGURE 2
Windows for clinically feasible application of different types of therapeutic agents for COVID‐19. Time course of symptomatic progression in lethal COVID‐19 simplified from Zhou et al. (2020), annotated with time windows indicating when different therapeutic interventions that might realistically be applied
See this image and copyright information in PMC

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