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SARS-CoV-2 zoonotic/reverse zoonoses animal model - SE0557

Coronavirus disease 2019 (COVID-19) is an infectious viral zoonotic disease caused by beta-coronavirus SARS-CoV-2, ACDP3/SAPO unclassified agent requiring bio-containment level (BCL) 3 when virus amplification and bio-aerosols are employed. Coronavirus pathogens are capable of causing human illness ranging from common colds to severe diseases, including Middle East Respiratory Syndrome (MERS-CoV), and Severe Acute Respiratory Syndrome (SARS-CoV) (Cui et al., 2019). COVID-19, was declared a global pandemic by WHO on 11 March 2020. Coronaviruses are known to infect humans, birds and mammals with transmission through fomites, airborne or faecal-oral routes. Epithelial cells in the respiratory and gastrointestinal tract are the primary target cells, with an estimated incubation period ranging from 2–14 days, or longer. Shedding of virus can be very variable from one to several weeks (49 days in a human longest currently recorded). The predominant route of transmission of COVID-19 is via aerosol transmission or contact of contaminated items with mucous membranes. The current spread of COVID-19 is a result of human-to-human transmission (ECDC Report). To date, there is no evidence that companion animals play an important role in COVID-19 epidemiology. There have been reports of infections detected in dogs, cats and tigers that have had direct or indirect contact with positive human cases, indicating cases of reverse zoonoses, which were sub-clinical or mild in nature (Shi et al., 2020; OIE Advisory Group). Public Health and Veterinary Services are using a One Health approach to share information and conduct risk assessments for a person with COVID-19 reporting contact with companion or other animals (key species; dogs, cats (including large felids), ferrets, primates or pigs). The ferret has proven to be a good model for mild-moderate human and animal disease as a result of infection with SARS-CoV-2 viruses based on modest clinical presentation at 1-2 weeks post exposure, viral shedding from the upper (nose and throat) and lower (lungs) respiratory tracts over 1-3 weeks, and gastrointestinal tract (rectal) over a shorter period (Kim et al., 2020; Richard et al., 2020; Shi et al., 2020). The major objective of this proposal is to adapt the APHA ferret-influenza A virus model (animal/human), incorporating the PHE-Porton ferret-SARS-CoV-2 model (human), and establish full COVID19 research and diagnostic capability at APHA-Weybridge using the BCL3 animal and laboratory facilities. This first phase is a challenge/clinical sample/reagent pilot study to build capability and extend the in vitro tool box (molecular/histochemistry) projects undertaken in March 2020. This work will allow more advanced study designs (including assessment of vaccines and therapeutics) to be undertaken in the near future. The design of the in vivo pilot will incorporate infection of ferrets with a suitable virus dose to confirm clinical observations, virus shedding profiles, viral load in organs and immune responses. In addition, environmental samples will be collected to determine if virus can be detected on animal fur, in feed and water and on hard surfaces (e.g. metal/plastic). Reagents that will be made available for future funded work include carnivore-adapted virus, positive control antibodies for serological test development as well as positive control tissues for virology, histopathology and immunology studies with relevance to animal and human investigations. This information and capability will be taken forward as evidence of APHA-Weybridge’s competence in this critical new and emerging zoonotic disease research area with UK and European partners providing further added value for Defra. Our large ferret capacity is greater than any other location in the UK and most facilities across the world and allows us to undertake complex multi-armed designs for disease interventions and/or duration of study.
1.0 Establish the ferret/SARS-CoV-2 model at APHA-Weybridge 30/04/20
Skill development (e.g., training to enable novel skill acquisition and capability; development of existing/novel skills base)
2.0 Create positive control reagents – virus, infected tissues and polyclonal antibodies 15/05/2020
Disease threat and mitigation (e.g., pathogen characterization; diagnostic development; optimization and validation of tests)
3.0 Characterise host and virus pathogenesis parameters 29/05/2020
Knowledge acquisition (e.g., pathogenesis; epidemiology; transmission; host competence etc)
4.0 Assess contamination of environmental samples – animal fur, feed and surfaces 29/05/2020
Environmental and safety (e.g., inactivation work, sampling techniques, pathogen matrix evaluation)

Establishing the ferret model of COVID19 will allow APHA to play a part in disease prevention and control from both human and animal perspectives. Assessment of developmental vaccines and therapeutic interventions, and assess host responses with respect to infection duration (waxing and waining of shedding), and re-infection possibilities and parameters, plus host age, sex and metabolic/underlying conditions. The implementation of COVID19 response (diagnostics and applied research) allows us to test our responsiveness to ‘Disease-X’ scenarios, adapting our skills sets to novel zoonotic disease challenges on behalf of Defra and the wider UK government. Provide public reassurance that .Gov.UK science is responsive and productive.

Time-Scale and Cost
From: 2020

To: 2020

Cost: £25,035
Contractor / Funded Organisations
APHA (Animal and Plant Health Agency)
Fields of Study
Animal Health