As the pandemic rumbles on, with more and more people being infected day by day, our colleagues in human medicine are frantically searching for effective treatments, controls, and (hopefully!) a vaccine. The front-line health workers are also trying to maintain healthcare standards in very difficult circumstances – and good luck to them! Unfortunately, with the exception of the brief spikes of activity around SARS and MERS, coronaviruses haven’t really been on the human medical profession’s radar.
For those of us in the veterinary profession, though, coronaviruses are a routine part of our work, in both the companion animal and farm animal sectors. Over the years we’ve picked up a lot of experience in dealing with them. I’ve written about One Health before – and this is a classic example of a situation where we all need to learn from each other!
Why is this an issue?
Well, increasingly we’re seeing human medics bumping their heads against the same issues that we’ve been facing for years – and potentially not expecting them. There are also concerns that much of the work already done in the veterinary field is now being needlessly duplicated. Slowing down the development of drugs, and potentially leading researchers astray. For example, one professional newspaper, the Vet Times, this week led with a headline “Vet science ‘being ignored’ in quest for COVID-19 drug”.
Now, nowhere am I saying that the veterinary profession has all the answers – we certainly haven’t defeated all our coronavirus enemies yet! However, our experience might be able to suggest that some avenues are potentially more profitable than others.
What coronaviruses affect animals?
There are loads of different ones. Among the more important are Canine Enteric Coronavirus (CCoV), Infectious Bronchitis Virus (IBV) in poultry, the various swine coronaviruses (including transmissible gastroenteritis virus of swine, TGEV, and the more severe porcine epidemic diarrhoea virus (PEDV)), Bovine Coronavirus (BCoV) and Feline Coronavirus (FCoV), the causative agent behind the fatal condition Feline Infectious Peritonitis. Of course there are many, many more, but we can draw certain common factors from these viruses.
Common Coronavirus issues
Impacts of coronaviruses
Coronaviruses primarily affect two systems – the gastrointestinal tract (e.g. CCoV, TGEV and PEDV and FCoV), or respiratory tract (e.g. IBV). Sometimes, they affect both (BCoV and possibly Covid-19 in humans).
The immunity to coronaviruses tends to be short lived, and animals may be repeatedly infected (this is particularly true of FCoV); and protection is often provided by antibodies on the mucosal surfaces of the gut or respiratory tract (IgA). Circulating antibodies in the blood (IgG) do not seem to consistently provide the same protection, although they are markers of infection.
To complicate matters, most coronaviruses cause relatively mild symptoms in most individuals. But in some cases (FIP is a good example of this) the presence of high levels of antibodies seem to be a risk factor for triggering a much more severe disease. This seems to occur due to a phenomenon known as “Antibody Dependent Enhancement” whereby the antibodies bind the virus, but instead of killing it, simply allow it to infect cells in a different way, leading to an inflammatory storm.
Problems managing coronaviruses
Making life more complicated, coronaviruses pop up all over the place. Often by species transfer – for example, TGEV in pigs appears to have come from a mutant canine coronavirus; and itself later changed to become a more virulent form, PEDV.
Finally, reliable vaccines against animal coronaviruses have been very difficult to make. While there are a range of vaccines available against the gastrointestinal coronaviruses, they are mainly to protect newborn calves and piglets by boosting antibody levels in the mother’s colostrum. Vaccines to protect older or adult animals are few and far between, and often (like the CCoV vaccine) of limited effectiveness.
The best solution we’ve found is to try and keep the outbreaks from starting in the first place, with really good biosecurity and never mixing groups of animals of different ages in a high stress environment… And I’m not sure that’s really transferable to humans!
So, what lessons can be learned?
Well, our experience suggests that there’s good news and bad news.
The good news – treatments
In the last 18 months or so there have been a number of really promising studies into various treatments for FIP – a disease that seems analogous in many ways to the severe acute respiratory syndrome form of Covid-19.
Firstly, a series of drug trials have led to what appears to be a relatively safe and effective antiviral agent that is effective at suppressing the virus in affected cats. Called (catchily) GS-441524, the initial data have been very promising. However, there have only been 2 studies published so far, on a total of 41 cats. While the drug might be really useful – it isn’t proven yet. Interestingly, the active component of the drug is identical to the human product remdesivir (which is being investigated by human medical researchers), but is reportedly much cheaper and easier to manufacture. Perhaps this is research that is worth following up?
Secondly, there are reports that cytokine blockers, used in dogs against skin allergies and experimentally in cats against FIP, might be useful in “calming the storm” of hyper-inflammation. This is work that is being followed up in hospitals.
The bad news – vaccines
Vaccines against coronaviruses in animals are, as we saw above, rather limited. This isn’t because no-one’s tried to make them or put money in – they have! A good FCoV or FIP vaccine would be worth serious money. For example, as would less limited vaccines for use in farm species. However, the short duration of immunity, and the different types of immunity, have been a significant barrier. The Canine coronavirus vaccine is a good example – it generates strong blood antibody counts, but does not protect against infection. This seems to be because mucosal antibodies are needed for protection, but these are much harder to generate.
However, they’re not impossible. The respiratory coronavirus vaccines available against IBV in chickens can definitely reduce severity of signs. The problem is that it may not protect against infection. And this is an issue where, I hope, vaccine researchers and manufacturers are constantly on the phone to their veterinary colleagues!
The bottom line…
Coronaviruses are really hard to manage – we’ve found that out the hard way in the veterinary world. BUT if we pool our resources, there are now drugs that might make all the difference, and perhaps we can crack the vaccine problem too. This is a genuine “One Health” issue, and as health professionals, we really can all learn from each other on this one!