Ground-breaking research on antivirals

Dr Pedersen, a pioneering feline medicine specialist and virologist in the USA, published a study in 2018 (Pedersonet al 2018) showing that an antiviral drug called GS-441524, which interferes with the multiplication of feline
coronaviruses, was safe and effective for the treatment of cats with wet FIP (ocular and neurological FIP cases werenot included). In this study 25/26 cats treated for 12 weeks or longer with injectable GS-441524 appeared to becured from FIP (1 cat subsequently died of an unrelated heart problem). A further study by Dr Pedersen’s group in2019 (Dickinson et al 2019) showed that GS‐441524 was also effective at higher doses in cats with neurological FIP.
Until these Pedersen studies, no drug had been found that showed such promise for long term survival and apotential cure for FIP. More recently studies have been published showing effective treatment with oral formulationsof GS-441524.
As no licensed GS-441524 product was available, many black-market formulations of GS-441524 became available
for internet sale. Not only were these formulations incredibly expensive, but they were also potentially dangerous as
the amount of medication, or even the exact formulation of the medication in these drugs, was not known. In many
countries of the world, it is illegal for vets to buy these products and it is illegal for owners to administer theseproducts to their cats.

What treatment is now legally available and how effective is it?

GS-441524 (given orally as tablets) and its parent drug remdesivir (given by intravenous or subcutaneous injection)
are now legally available as antivirals for cats with FIP as ‘specials’ preparations in the UK since August 2021. The
minimum treatment course required is 12 weeks, so it is long and costly, and it is important to be aware thatsuccessful treatment cannot be guaranteed and that relapses with repeat treatment courses may be required.
Additionally, the dose of antivirals given must be increased as weight is gained during recovery, again influencing
cost. The dosages of the antivirals required also vary with the type of FIP, with neurological and ocular FIP needing
the highest dosages, again increasing cost. As owners, you also need to commit to being able to administer theantivirals to your cat, which can be difficult with a long treatment course.
Vets in Australia have had access to oral GS-441524 and injectable remdesivir for a few months longer than those of
us in the UK, and between us we have now treated over 1500 cats. There is still a lot of research ongoing but atpresent the success rate is phenomenal with over 85% of cats responding to treatment following at least 12 weeks
of treatment, with long term remission. Cats do need to be closely monitored both during and after the 12 weeks oftreatment and your vet will advise you on the monitoring required (likely regular examinations, weight checks andpossibly some blood tests too).

What do I need to do if I need more help?

Your vet will be best placed to help and treatment of FIP is ateam approach between you and your vet doing the best foryour cat. As antiviral treatment of FIP is new, a team of feline
experts have set up an email help service for vets at
fipadvice@gmail.com – please ask your vet to email for help ifthey need to discuss diagnosis or treatment of a suspectedcase of FIP.
It is illegal for vets to advise on patients that are not under
their direct care, so please make sure it is your vet who emails
the feline expert team as sadly it is not possible for the feline
expert team to provide advice direct to owners.

References
Hartmann 2017. Coronavirus Infections (Canine and Feline), Including Feline Infectious Peritonitis. Chapter 224 p984-991. In Textbook of InternalMedicine, 4th Edition. Ettinger.
Kennedy and Little 2012. Infectious diseases, Chapter 33 p1038-1047. In The Cat. Clinical Medicine and Management, Little.
Pederson et al 2019. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious
peritonitis. J Feline Med Surg.21: 271–281
Dickinson et al 2020. Antiviral treatment using the adenosine nucleoside analogue GS‐441524 in cats with clinically diagnosed neurological feline
infectious peritonitis J Vet Intern Med. 2020 Jul; 34(4): 1587–1593

FELINE INFECTIOUS PERITONITIS (FIP)
INFORMATION FOR CAT OWNERS
By Dr. Stephanie Sorrell, Prof. Séverine Tasker, Dr. Sam Taylor,Dr. Emi Barker, and Prof.Danielle Gunn-Moore

What is FIP?
FIP, also known as Feline Infectious Peritonitis, is a truly
devastating disease. It is caused by a feline coronavirus, which
although belonging to the same family of viruses as COVID-19, iscompletely different. Feline coronaviruses infect cats alone andcannot be transmitted to humans.

Email help service for your vet: fipadvice@gmail.com

How does feline coronavirus differ from FIP?
Feline coronavirus itself is not the same as FIP. Feline coronavirus is a very common viral infection found in catsworldwide, especially in multi-cat households, with more than 90% of cattery/breeding cats, and up to 50% of cats insingle cat households, showing evidence of infection (Hartmann 2017). Feline coronavirus infection usually causes noclinical signs in cats but occasionally it can result in mild diarrhoea, especially in younger cats, as the virus multiplies in
the cells of the intestinal tract. The virus may survive outside of the cat in the environment for up to 7 weeks in dryconditions, however, it is readily destroyed by common detergents and disinfectants (Kennedy and Little 2012).
As feline coronavirus usually causes no clinical signs, we don’t tend to worry too much about this infection. However,in a very small percentage of infected cats, feline coronavirus infection can develop into the disease of FIP; this isbelieved to occur when the feline coronavirus genetic information changes (mutates), allowing it to cause FIP when
the cat’s immune response does not prevent FIP from developing.

Which cats are most at risk of developing FIP?
We do not know why in certain cats the coronavirus can mutate to cause this awful disease.
Here are the high-risk groups:
Less than 2 yrs
usually developing
the disease between
3-16 months

Pedigree catsMulticat households

Male cats are atslightly increasedrisk

How does FIP present?

As the samples that confirm a diagnosis of FIP are usually quite difficult to collect (for example generalanaesthesia and surgery may be needed), vets often try and be as confident as possible in making a diagnosis of
FIP based on facts and results obtained more easily. These include your cat’s age and breed, its history (anyrecent stress such as neutering/moving house/rehoming may increase the chance of FIP developing), clinicalsigns (such as fluid in abdomen or chest) and certain blood changes such as high protein levels, liver enzymes andmarkers of inflammation (such as AGP-1). If fluid is present, your vet will likely obtain a sample of the fluid andlook to see if it has the appearance expected with FIP (most often straw yellow in colour, thick and sticky) before
sending it to the lab to look at the contents of the fluid. This diagnostic investigation is really important to help
rule out other serious conditions such as liver disease, other infections and cancers that can mimic FIP.
It is therefore necessary to undertake many tests to try and determine if FIP is likely, and even then, a diagnosisof FIP may not be confirmed. It is important for your vet to be confident that FIP is likely before starting antivirals
as the treatment course is very prolonged and expensive, so it should be reserved for cats with highly
likely/confirmed FIP disease. In addition, inappropriate use of antivirals in cats without FIP could lead tocoronavirus resistance problems, meaning that cats with FIP may no longer be able to respond to these novel
antiviral treatments.

Which laboratory tests are NOT helpful to make a diagnosis of FIP?

"Wet FIP"
in which fluid develops in"Dry FIP""Neurological FIP"

"Ocular FIP"a body cavity – especiallywhen no fluid forms

Brain and/or spinal

affecting the eyes

the abdomen and/orYour vet will perform several routine tests including blood, urine tests, checking the back of the eye, and imagingof chest/abdomen. If any fluid has developed, then obtaining and testing a sample of the fluid (from theabdomen or chest) is very useful to help support a diagnosis of FIP. Further testing that may be required includes
sampling of any abnormal organs e.g., a needle sample of the liver, kidneys or lymph nodes (glands) in theabdomen. The tests which confirm a diagnosis of FIP are those which demonstrate the presence of feline
coronavirus particles in association with abnormalities (pathology) that are consistent with FIP. These tests arecalled immunohistochemistry (done on biopsy samples) and immunocytochemistry or immunofluorescence (IF)(done on fluid samples or needle samples from organs such as the liver, kidney, and lymph nodes). Moreadvanced tests such as brain scans (MRI) and further fluid sampling may also be indicated if your cat has
neurological signs (such as fits or a wobbly walk).

cordchest

Antibody tests (serology)
many cats have been infected with feline
coronavirus and the presence of antibodies justshows that the cat has been exposed to acoronavirus but doesn’t tell you if the coronavirus isassociated with FIP. Indeed, in some cats with severe
FIP disease, their antibody levels are low or evennegative as the antibodies are ‘used up’ in the FIP
disease process.

How was FIP treated in the past?
Testing for FIPYour vet will be best placed to decide which diagnostic tests are appropriate for your cat to see if FIP is a possible
diagnosis. As FIP can present with so many different clinical signs, it is impossible to say which tests are mostappropriate as this will vary. It is also important to understand that being able to absolutely confirm a diagnosis of FIP isdifficult, and tissue samples are usually needed (e.g., lymph node removal or biopsies) necessitating invasive
procedures.
Email help service for your vet: fipadvice@gmail.com

Previously treatment for FIP was not effective and after
diagnosis most cats either died or were put to sleep. Manydifferent treatments were trialled including medications suchas steroids, interferon, propentofylline and polyprenyl
immunostimulant. But most studies reported poor survival
rates and no convincing long-term effect of treatment.

Email help service for your vet: fipadvice@gmail.com

Testing faecal (poo) samples
for coronavirus is also unhelpful because
many cats are infected with coronaviruses
and shed them in their faeces; the tests
cannot distinguish between cats with andwithout FIP.