Coronaviruses, shared by both animals and humans
Although coronaviruses have been thrust into the spotlight with COVID-19, this family of viruses has long been known, mainly for the diseases they cause in animals. These vary, but mainly affect the respiratory and digestive systems. Over the last twenty years, coronaviruses have been responsible for three severe acute respiratory syndrome epidemics in humans: SARS-CoV in 2003, MERS-CoV in 2012 and finally SARS-CoV-2 in 2019. These three emerging viruses all descend from viruses isolated from different species of bats. They probably crossed the species barrier by first jumping to another mammal and then moving on to humans. ANSES has been conducting research with its institutional partners on the mechanisms of cross-species transmission of coronaviruses for many years.
What are coronaviruses?
Coronaviruses form a large family of many different viruses. They affect numerous species of mammals and birds, and some can be transmitted to humans or be specific to them. They can cause a wide range of diseases, but mainly affect the respiratory and digestive systems. What they have in common is that they are highly transmissible. There are many coronaviruses known in the animal health field, and they can be found in dogs, cats, pigs, ruminants, horses, camels, birds or wildlife (especially bats).
What diseases do they cause?
The severity of the infections caused varies greatly. Infections due to coronaviruses are common in veterinary medicine. They can have a significant economic impact, particularly in herds or flocks of young ruminants, pigs, chickens and turkeys. For example, poultry can be infected with the avian infectious bronchitis coronavirus, while there are coronaviruses that specifically infect the digestive tract of turkeys and guinea fowl. Pigs are susceptible to porcine epidemic diarrhoea virus, transmissible gastroenteritis virus and porcine respiratory coronavirus. Cats can contract a fatal disease called feline infectious peritonitis virus, while young horses and cattle are affected by digestive disorders. Lastly, infection by these viruses has an unknown effect on wildlife (bats, hedgehogs, rodents, etc.).
How are coronaviruses transmitted from one species to another?
The COVID-19 epidemic is a reminder that mutations in coronaviruses can sometimes enable them to change host. Indeed, they can evolve rapidly through frequent mutations in their genetic material. They can also recombine, i.e. exchange portions of the genome. This can happen if two different coronaviruses co-infect the same host cell. This evolution may give them the ability to reach new target organs or adapt to new host species. These new viruses can be particularly pathogenic because the new host species is not accustomed to them and does not have the necessary immune defences to respond effectively to the new infection. However, while these events have been detected quite often in the recent past (the virus responsible for COVID-19 is the third coronavirus to pass from animals to humans in the last twenty years or so), this phenomenon is not new: one of the viruses responsible for the common cold in humans, the OC43 coronavirus, is estimated to have evolved from transmission of bovine coronavirus to humans in the late 19th century.
What is ANSES doing about coronaviruses?
ANSES is conducting various studies on coronaviruses in poultry, pigs, cats and wildlife. It has stepped up its work on the subject in response to the COVID-19 epidemic, particularly on the possibility of interspecies transmission and on treatment and diagnostic techniques using methods that could be useful in a comparative virology approach. Here are a few examples:
Understanding the viruses circulating in animals
Three ANSES laboratories, the Nancy Laboratory for Rabies and Wildlife, the Maisons-Alfort Laboratory for Animal Health and the Ploufragan-Plouzané-Niort Laboratory, took part in the ANR's EPICOREM project from 2014 to 2018. This work, coordinated by Caen University Hospital, revealed the great diversity of coronaviruses circulating in domestic and 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 population.
The Maisons-Alfort Laboratory for Animal Health is currently coordinating the European MuseCov project, which also involves two other ANSES laboratories (Ploufragan-Plouzané-Niort and Nancy). It seeks to improve understanding of the diversity of coronavirus strains circulating in animal populations, including SARS-CoV-2. The aim is to improve knowledge of the dynamics of coronavirus infections in various animal populations and be able to rapidly detect the emergence of particularly pathogenic variants.
Lastly, ANSES’s Ploufragan-Plouzané-Niort Laboratory is exploring the mutations and molecular mechanisms that accompany the transmission of avian coronaviruses in different poultry species or allow genetic rearrangements in porcine coronaviruses.
Improving understanding of inter-species transmission mechanisms
The Virology Joint Research Unit (ENVA-INRAE-ANSES) of the Maisons-Alfort Laboratory for Animal Health is conducting a research project, in conjunction with an Inserm team, on the molecular determinants of pathogenicity of feline coronavirus. This virus can cause a fatal disease in cats called feline infectious peritonitis. The project is studying the mechanisms that promote the crossing of the interspecies barrier. This work is being carried out in collaboration with the Nancy Laboratory for Rabies and Wildlife on possible interactions with coronaviruses found in wildlife, and the Ploufragan-Plouzané-Niort Laboratory on avian coronaviruses.
Developing diagnostic and treatment techniques
The Ploufragan-Plouzané-Niort Laboratory is developing methods for the molecular or serological diagnosis of avian and porcine coronaviruses. A project that began in late 2019 is seeking to develop a serological test (ELISA) to detect antibodies produced in response to infection with the European strain of turkey coronavirus (TCoV), as none is available at present.
The Nancy Laboratory for Rabies and Wildlife has developed methods for the molecular and serological diagnosis of SARS-CoV-2 infection in mink. These were used to carry out the first survey in French farms, which detected one of the country's four farms as contaminated, with more than 90% of the animals having a positive serologic response.
Regarding treatments, the Laboratory for Rabies and Wildlife participated in the Timing project, funded by the ANR and coordinated by INRAE. It 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 these interferons 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 Timing project showed in animal models that only very early administration of interferons (before or just after infection) was beneficial, and that contrary to what was assumed, late administration was not deleterious.
Understanding the genetic evolution of coronaviruses
Coronaviruses have great potential for evolution through mutation, recombination and selection events. Since 2018, the Ploufragan-Plouzané-Niort Laboratory has been studying the genetic evolution of chicken (IBV) and turkey (TCoV) coronaviruses. In particular, the unit has been examining 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.
Assessing the transmissibility of COVID-19 from animals to humans
The Agency has also been asked to issue opinions on the risks of transmission of the SARS-CoV-2 virus from animals to humans. It determined that although some species, such as cats, ferrets, mink and hamsters, were susceptible to COVID-19, domestic animals and wildlife play no role in sustaining or spreading SARS-CoV-2 in France, where the spread of the virus is due to human-to-human transmission by the respiratory route. However, there is a risk of development of an animal reservoir. ANSES therefore recommends exercising particular vigilance during contact between humans and species capable of harbouring the virus (cats, mink, etc.), in conditions of high animal density and close proximity between animals and humans, especially in closed or confined environments.
A reference mandate for monitoring SARS-CoV-2 in wastewater and sewage sludge
The Laboratory for Hydrology has been National Reference Laboratory for the monitoring of SARS-CoV-2 in wastewater and sewage sludge since late 2021. This surveillance is designed to supplement the tools already available, particularly in a context of low viral circulation, in order to detect the virus's (re)emergence in the population at an early stage. The laboratory's responsibilities include harmonising the methods used to detect the virus and assessing the abilities of the laboratories tasked with carrying out the analyses.
Avoiding exposure to coronavirus in the workplace
As part of its occupational health missions, ANSES has also issued recommendations on measures other than those relating to healthcare to be adopted to avoid contamination in the workplace. It is also conducting a research project, SACADA, to determine how the virus circulates in meat-processing plants and suggest appropriate preventive measures. Because of the characteristics of these work environments, notably the cool, moist conditions and the strenuous physical labour, they are particularly conducive to the spread of the virus between workers.