Working at the interface between human and animal health, in the spirit of "One Health", ANSES's laboratories help provide effective, rapid responses to issues of applied research that can be implemented immediately. As an example, since the start of the COVID-19 pandemic, ANSES has been deploying its research teams, its expert knowledge of zoonoses and animal coronaviruses and its network of laboratories to improve knowledge on SARS-CoV-2 and respond to questions that have arisen from this crisis. Here is an overview of the various projects undertaken by the Agency.
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Updated on 15/02/2021
What is ANSES doing?
Several of ANSES's laboratories have been working on animal coronaviruses for many years. For example, their teams took part in the ANR project EPICOREM from 2014 to 2018. This work, coordinated by the Caen University Hospital, revealed the great diversity of coronaviruses circulating in wild animal populations in France and Europe. New viral species were described in humans, domestic animals and wildlife. At the same time, researchers monitored the evolution of a Betacoronavirus, a SARS-CoV sister group, within a bat colony. This part of the project has led to a greater understanding of the dynamics of the virus’s evolution within a host.
The Maisons-Alfort Laboratory for Animal Health is also conducting several research projects on coronaviruses, including one on the therapeutic potential of new antiviral drugs against coronaviruses in general. The study is focusing on a human coronavirus responsible for respiratory infections (HCoV-229E) as well as a feline coronavirus (feline infectious peritonitis virus) responsible for a fatal disease in cats. The most effective drugs are being tested in vivo in naturally infected cats for which no therapy is currently possible. These data will enable the therapeutically effective dose against a given coronavirus to be assessed.
Meanwhile, in Ploufragan, the Virology, Immunology and Parasitology in Poultry & Rabbits (VIPAC) Unit has been working on avian coronaviruses for over 30 years. Since 2018, the unit has been studying the genetic evolution of avian coronaviruses in the presence or absence of vaccination. The results have shown that the genetic evolution of an avian coronavirus is very rapid (detected from the first passage in non-vaccinated subjects) and differs between vaccinated and non-vaccinated subjects. These results have shed light on how coronaviruses evolve in the presence of vaccine immunity. Lastly, the Viral Genetics and Biosafety (GVB) Unit is home to the National Reference Laboratory for porcine epidemic diarrhoea (PED), a disease caused by a porcine coronavirus.
Work carried out since the start of the COVID-19 crisis
The ANSES laboratories have been busy since the start of the pandemic, launching several research projects.
At the Laboratory for Animal Health
The Virology UMR (an ANSES-INRAE-ENVA joint research unit) has particularly been involved in initiating the following projects:
- A scientific study on the potential infection of pets, especially cats. Following recent international publications describing a few cases of contamination in domestic carnivores, the VIRO UMR launched a scientific study on the possible transmission of the SARS-CoV-2 virus to cats. Veterinary practitioners from Île-de-France were invited to submit samples collected from suspect animals (cats in close contact with a person infected with COVID-19 or cats showing acute respiratory symptoms). The aim of this study was to improve existing knowledge on how SARS-CoV-2 is transmitted and how it behaves in cats. It led to detection of the first infected cat in France. This sick cat, which ended up recovering, had likely been contaminated by its owner. An article on the topic was published in the journal Transboundary and Emerging Diseases.
- The SARS2BlockEntry project (Engineering nanobinders to block SARS-CoV-2 entry). Financed by the National Research Agency (ANR) and coordinated by the National Research Institute for Agriculture, Food and Environment (INRAe), it aims to develop drugs to block SARS-CoV-2 entry into cells, using hamsters as the animal model.
- Work on potential central nervous system infection with SARS-CoV-2. A large number of patients with severe forms of COVID-19 have presented with neurological symptoms, suggesting that the virus may invade the central nervous system. The virus’s ability to infect these cells will be studied using central nervous system cells handled in the laboratory.
- The MUSECoV project, selected by the ERA-Net ICRAD (International coordination of research on infectious animal diseases) call for projects and coordinated by Sophie Le Poder, from the Alfort National Veterinary School and also part of the UMR VIRO. It seeks to improve understanding of the diversity of coronavirus strains circulating in animal populations, including SARS-CoV-2. The aim is to better understand the dynamics of coronavirus infections in various animal populations and therefore to rapidly detect the emergence of particularly pathogenic variants.
At the Laboratory for Rabies and Wildlife
- The Timing project, funded by the ANR and coordinated by INRAe. This ongoing project is studying the beneficial or deleterious effect of type I interferons (IFNs). These are small proteins produced naturally in the body in response to a viral infection. Numerous studies have shown that the body’s failure to produce type I IFNs may be associated with the development of severe forms of COVID-19. However, type I interferons are not always beneficial, as they can cause excessive inflammation. The balance between the beneficial and detrimental effects of type I interferons needs to be studied in the case of COVID-19. The objective of the Timing project is to determine the appropriate moment to administer IFN treatment, in order to eliminate the infection and reduce the development of COVID-19 symptoms and lesions, without causing excessive inflammation.
- The laboratory is responsible for the EvoZOOne project, selected by the World Health Organization as part of its R&D Blueprint. Its aim is to increase knowledge on SARS-CoV-2 at the human-animal interface relating to the evolution of SARS-CoV-2 and the assessment of zoonotic potential. The laboratory is also involved in a second WHO R&D Blueprint project on viral persistence under different environmental conditions, led by the ANSES Laboratory for Hydrology, which is investigating the persistence and behaviour of SARS-COV-2 particles in aqueous environmental matrices.
At the Ploufragan-Plouzané-Niort Laboratory
The Virology, Immunology and Parasitology in Poultry & Rabbits (VIPAC) Unit and the Viral Genetics and Biosafety (GVB) Unit have been working to acquire the knowledge needed to combat the pandemic in several areas:
- Identifying coronavirus inactivation treatments for surgical face masks: in a collaboration with Grenoble University Hospital, the French defence procurement agency (DGA), Tours Hospital and various private partners, and thanks to access to the facilities of the Dupuy de Lôme Research Institute (University of Southern Brittany), a partner of ANSES within the AgriFood Transition Carnot Institute, the Ploufragan Laboratory assessed the efficacy of various virucidal treatments applicable to respiratory masks, using two animal coronavirus models (avian infectious bronchitis virus and porcine epidemic diarrhoea virus). The goal of this work is to help identify safe solutions that can be implemented by both professionals and private individuals, to sanitise their masks and make them fit for reuse.
- Developing a new specific serological test for European turkey coronavirus: this project, conducted in partnership with the EPISABE Unit and the CTPA ZOOPOLE Développement centre of expertise, is receiving financial support from the AgriFood Transition Carnot Institute. Ultimately, it will be possible to apply this knowledge to the development of tests to detect other coronaviruses.
- Studying the persistence of coronaviruses in coastal waters: as part of the ANR's RA-COVID-19 call for projects and in collaboration with the French Research Institute for Exploitation of the Sea (Ifremer), a project has been submitted to study the survival and persistence of coronaviruses in coastal waters, as well as their bioaccumulation in molluscs. Porcine coronaviruses will be used as models to replace the SARS-CoV-2 coronavirus for the preliminary studies.
- Conducting diagnostic testing for SARS-CoV-2: as public veterinary research laboratories, the virology units on the Ploufragan site have been called on by the Brittany Regional Health Agency to build SARS-CoV-2 diagnostic capacities in Brittany. If needed, the laboratory will be able to perform up to 360 RT-PCR analyses per day. This mobilisation of veterinary laboratories to control the COVID-19 pandemic supports the concept to focus efforts on "One Health" combining veterinary and human health.
Interesting animal models for studying new therapeutic approaches
The Nancy, Lyon, Ploufragan and Maisons-Alfort Laboratories have responded to various calls for projects, in collaboration with hospital, INRAe and veterinary school research teams, to develop ferret and hamster animal models in order to test new therapeutic approaches and investigate host-pathogen relationships. The results obtained with ferret models in Nancy and hamster models in Lyon are highly relevant and complementary. The effects in ferrets resemble those observed in humans, especially in the upper airways, with clinical effects visible seven to 10 days post-inoculation. This animal model is also advantageous in that samples such as nasal wash fluids can be collected without having to sacrifice the animals; moreover, it enables viral loads to be monitored over time. Conversely, the hamster model shows very rapid and strong signs of lung damage, from two days post-inoculation. This model is not as conducive as the ferret model to sampling without sacrificing; however, it is an excellent model that is easy to implement using short protocols (lasting around one week) to analyse candidate drugs having a possible therapeutic effect on SARS-CoV-2. The validation of these animal models has led the Nancy and Lyon Laboratories to submit several requests and projects seeking to better understand the pathogenesis of COVID-19 and test therapeutic compounds and vaccines in collaboration with numerous institutes.
Prepare for the emergence of other coronaviruses
The Nancy, Ploufragan and Maisons-Alfort Laboratories are also working together to study under what conditions and for what reasons coronaviruses may cross the species barrier and thus jump from one animal species to another. This study will help them better prepare for the emergence of new coronaviruses. This subject will be dealt with within the framework of the One Health EJP, with the forthcoming organisation of a Joint Integrative Project (JIP) entitled "COVRIN-SARS-CoV-2 Research Integration & Preparedness for Future Coronavirus Outbreaks". This JIP aims to integrate the coronavirus research activities of all the One Health EJP partners. The project will have two main operational objectives: to identify the factors determining emergence and spread of SARS-CoV-2 and to generate data and build models for assessing coronavirus risks.
Lastly, the Agency's work for the "One Health" project – based on the three pillars of human, animal and environmental health – and its involvement in the scientific management of the One Health field of major interest (DIM) have sustained dynamic research into coronaviruses in domestic carnivores and supported new anti-coronavirus therapeutic approaches. They have also helped raise €1 million to support research during this crisis.