We don’t talk a lot about antiviral resistance in animals, particularly compared to antibacterial resistance, primarily because we don’t use antivirals a lot in animals – but we do use some.
When we use any anti-infective medication, we have to think about the risks of resistance developing to that medication, and how we can try to optimize use in order to maximize clinical benefits while minimizing resistance risks. I say “minimizing,” not “eliminating,” on purpose, because we can rarely guarantee that there will be no risk. Usually we’re aiming for a risk that is low enough to justify use of the drug, and ideally we can lower that risk even further through some basic infection control practices.
I’ve written a lot over the last year about antivirals for the treatment of feline infectious peritonitis (FIP) in cats, since we now have incredibly effective options (now in Canada) for what was previously an almost invariably fatal disease. The antiviral drug GS-441524 (a relative of the COVID-19 antiviral drug remdesivir) is what we can now use in most regions to treat this disease. It’s a complete game changer.
However, anytime we have a revolutionary new anti-infective (be it for bacteria, viruses, parasites, fungi or other nasties), we need to take steps to try to maintain its effectiveness long term – primarily through good antimicrobial stewardship.
Are there scenarios where GS-441524 resistance could emerge in cats and be a problem? Yes.
Does our routine treatment of FIP pose much of a risk for emergence of antiviral resistance? No.
Those statements seem to conflict, but let me explain:
Feline infectious peritonitis is caused by feline coronavirus (FCoV), whichbis very common in cats, especially especially cats living in large groups. It infects the intestinal tract and then cats shed it in their feces, usually with no signs of illness The virus is spread cat-to-cat through fecal-oral exposure. The clinical disease (FIP) develops when an intestinal-dwelling FCoV mutates into a tissue-infecting FIP virus (FIPV) within that cat.
While FCoV is highly transmissible, FIPV is not traditionally considered to be transmissible between cats (though I’m not sure we can actually say there’s no risk of transmission; I think there is some cat-to-cat transmission risk, but it’s probably very low).
Antiviral resistance can emerge when a virus is exposed to an antiviral. Random mutations occur that allow viruses to resistant the action of the drug, and then the mutated virus multiplies while the susceptible version may die out. The key is what happens next, and that varies a lot depending on the disease.
A critical component of the risk assessment for GS resistance is that is that we don’t consider FIPV to be transmissible (or at least we consider it really rarely transmissible). So if GS resistance develops in a cat with FIP, while it could be very bad for that cat (because the infection won’t respond to the drug), the odds of that cat transmitting the resistant virus to another cat are very low, so the resistant virus would likely die out with the first host.
The main concern is if cats with intestinal FCoV infections are treated with GS, then resistance could develop in FCoV in the gut of a cat, and that resistant virus would be shed in feces and be transmitted cat-to-cat (like FCoV normally is) through the cat population. Then, if any of those cats develops FIP, the virus would already have GS resistance and wouldn’t respond to treatment.
That means that appropriate treatment of cats with FIP poses an exceptionally low risk of causing resistance issues. For there to be a significant problem, it would require rare cat-to-cat transmission of FIPV (or emergence of resistance of FCoV from a concurrent, unrelated FCoV infection in the intestine). The benefits of treatment massively outweigh this small theoretical risk.
Empirical treatment of cats for FIP (without a solid diagnosis) is also generally low risk of resistance. If the cat doesn’t have FIPV or FCoV, there’s no risk. It’s not like the situation with bacteria where there’s always a massive and diverse pool of bacteria in the body that could develop resistance through exposure as “bystanders” and where resistance genes can then be transmitted between different bacteria. If the cat doesn’t have FCoV or FIPV to start, it can’t develop resistant FCoV or FIPV. The only risk would be (as above) if there was a concurrent incidental intestinal FCoV infection.
Does use of GS in cats with enteric FCoV pose a risk of resistance? That’s a big “hell yeah!” from me. We don’t have data to prove it, but the last thing I want is to be treating lots of cats with highly transmissible enteric FCoV infections, because spreading resistant FCoV through the cat population is how we end up with a lot of dead cats from resistant FIP. The cost-benefit just doesn’t add up in this scenario. Enteric infections are mild or cause no disease at all, and we are not going to eradicate FCoV from the overall cat population, or likely even from a local cat population (e.g. cattery), using antivirals (the virus is just too common and transmissible to be thinking about eradication). So we’re talking about treatment with little to no clinical benefit and no eradication benefit, while posing significant risk of selecting for resistance to a game-changing drug that is currently saving countless feline lives. That makes no sense to me.
Are there any human health issues related to use of GS in cats?
GS is related to remdesivir, a drug used to treat COVID-19 in people, but transmission of antiviral resistance from FCoV to SARS-CoV-2 isn’t a risk. The only theoretical risk would be if a cat had FIP AND a SARS-CoV-2 infection at the same time, AND resistant SARS-CoV-2 emerges in the cat during treatment AND the cat then infects a person with it. That’s a really unlikely scenario, so the risk is negligible compared to risks from direct use of remdesivir in humans.
Use as little as possible but use enough. That’s my line for antibiotics, and it applies equally well to antivirals. We don’t want to miss treatment opportunities, but can’t be reckless either and jeopardize this incredible new opportunity to be able to treat this terrible disease.