11th November, 2020
Feline infectious peritonitis (FIP) is a viral disease caused by feline coronavirus (FCoV). This virus is a mutant of feline enteric coronavirus (FeCV) which cannot be easily defeated through a cat's natural immune response. FCoV will infect white blood cells and spread through the cat’s body. The disease is progressive and can be fatal if left unattended. It is estimated that this disease can kill 1.4% of cats, which is approximately 2.8 millions to 8.4 millions of cats, around the world .
FIP can be divided into two categories, the effusive (wet) form and the non-effusive (dry) form. Common symptoms of FIP include loss of appetite, fever, depression, and weight loss. Cats can evolve from one FIP form into another form from time to time.
Nucleoside analogue has been found promising in treating both effusive and non-effusive FIP. Professor Pederson and his colleagues discovered that a nucleoside analogue, GS-441524, is effective in treating FIP . Their research published in February 2019 demonstrated that 26 out of 31 cats were recovered from FIP, regardless of the form and age. Additionally, another study by Dickinson and his co-workers has proved that GS-441524 can be used to cure 3 out of 4 cats with neurological FIP .
In our clinical trial, we aimed to reproduce and improve the clinical results published by Dr. Pedersen’s research group. Eleven cats participated in our clinical trial. Dosages between 5-10 mg/kg of cat’s body weight were given based on the gravity of FIP infection. 11 cats were given our 15mg/ml solution. 1 cat was given our 17mg/ml solution.
1 cat, coded F2003W showed progress during the treatment as he gained weight from 2.9kg to 3.5kg. However due to severe liver damage, he was euthanized on doctor’s recommendation.
2 cats code F2001N and F2002N exhibited neurological symptoms prior to the treatment. They began treatment on our 15mg/ml GS-441524, but changed to another brand of GS with higher concentration of 17mg/ml after 20 days. The reason for this decision according to cat’s owners was that the daily injection volume using the 15mg/ml was too high for cats with severe neurological FIP symptoms. We created a 17mg/ml solution shortly after learning of their experience.
2 cats F2006O and F2004DN began treatment in late June and have completed only 10 days of treatment as of the time of this report. F2006O exhibited ocular symptoms and F2004DN exhibited neurological symptoms that affected cat’s mobility. Both cats showed noticeable improvements within just 10 days of treatment. F2006O gained weight after 2 injections and the eye began clearing up. F2004DN mobility improved after 5 injections.
2 recently participating cats (F2012O and F2013WN) are both relapse cases who were previously treated with other brands. They have been treated with our 17mg/ml GS-441524 and the results show that both cats experienced weight gain and fever was broken as the sign of recovery during the treatment.
Twelve FIPV infected cats were of ages range from 0.5 to 96 months. Two of the cats had non-effusive (Dry) FIP (F2010D and F2011D) while another three cats had effusive disease (F2003W, F2008W and F2009W). Three neurological (F2001N, F2002N, F2005N) and two ocular (F2006O, F2012O) cats have participated in this clinical trial, together with another two cats (F2004DN, F2013WN) demonstrating a combination of symptoms.. The breed of the participating cats are categorized in Table 1. The treatment was conducted at a dosage of 5.0 mg/kg q24h for 12 weeks. Initial and after treatment blood tests have been done on cat F2011D and F2013WN. Body weight and temperature were selected as two major indicators of FIPV treatment efficacy using GS-441524 solution.
Table 1. Breed type cats participating in this clinical trial.
3. Results and Discussion
3.1. Complete Blood Count (CBC)
Table 2. Blood test results before and after treatment.
Table 2 shows that the dry FIP infected cat (F2011D) has a lower than normal A/G ratio, which was attributed to the high serum globulin level . Both types of FIP infected cats have experienced a rise in A/G ratio after GS treatment. The increase in A/G ratio of the dry FIP cat is more prominent (75%) than its wet FIP counterpart (18%).
FIPV infection is also associated with abnormal serum protein level that was indicated by elevated total protein value. Cat F2011D was diagnosed with a total protein concentration of 94 g/L, which is higher than the upper limit of 87 g/L. After 25 days of treatment, this value dropped to 74 g/L. In addition, the dry FIP cat has also been diagnosed with hyperbilirubinemia (high level of total bilirubin), a medical condition that was not observed in the wet FIP cat. The elevation in blood bilirubin is not due to the liver disease, but rather the increased catabolism of red blood cells and slow clearance of hemoglobin breakdown products .
Although the wet FIP cat (F2013WN) is normal in terms of A/G ratio, total protein, and total bilirubin level, it possesses an extraordinarily high MCHC and hemoglobin level at the initial stage of treatment. These can be rationalized as the result of dehydration.
3.2. Weight Change
Weight gain has been observed in all types of FIP infected cats (Figure 1-4). This shows that the cats are regaining their appetite, which was lost owing to FIP viral infection. Cats, regardless of the type of FIP, gain approximately 1 kg after 40 days of treatment, with one dry FIP cat (F2010D) exceptionally lost weight after 30 days of treatment.
Figure 1. Weight change in FIP cats with neurological symptoms during treatment.
Figure 2. Weight change in dry FIP cats during treatment.
Figure 3. Weight change in wet FIP cats during treatment.
Figure 4. Weight change of ocular FIP cats during treatment.
3.3. Body Temperature
Figure 3. Body temperature of dry FIP cats for the first 28 days of treatment.
Normal body temperature of a cat is between 37.7 – 39.1 °C.
The body temperature of the dry FIP cats were monitored to evaluate the effectiveness of GS-441524 treatment. Figure 3 demonstrated that both of the dry FIP infected cats observed were having a higher temperature that close to having a fever. After the beginning of treatment, the body temperature of elder cat F2010D (2 years old) gradually decreases to the normal range and fluctuates within this range. No fever was detected in this cat for the 28 days monitoring period.
In contrast, cat F2011D had lesser fluctuation than the F2010D. Its body temperature remained at the higher end and eventually got a fever between day 8 to day 16. After 15 days of treatment, the cat began to respond to the treatment and its body temperature gradually fell back to normal range in the next few days. The temperature of this cat remains in the normal range for the rest of the monitoring period. This indicates that our GS-441524 solution is effective in treating FIP and resolves fever.
In conclusion, the results of this clinical trial demonstrated that our GS-441524 product is effective in treating effusive (wet) and non-effusive (dry) FIP. Dry FIP cat was found to have a different blood profile to that of the wet FIP. The dry FIP cat has suffered hyperbilirubinemia, high total protein, and low A/G ratio. Meanwhile, the wet FIP cat was detected with a high level of red blood cell destruction products. Both dry and wet FIP cats have gained weight during the recovery process due to the restoration of appetite. While body temperature can be used to monitor the course of treatment when fever was one of the symptoms of the infected cats. It was deduced that no single parameters can be used to diagnose and confirm the FIP viral infection in a cat. A combination of physical monitoring and blood test analysis need to be carried to confirm the FIP infection.
 Geoffrey Migiro, “How Many Cats Are There in the World?Philippines” WorldAtlas.com, 7 November, 2018, https://www.worldatlas.com/articles/how-many-cats-are-there-in-the-world.html. Accessed 6 Nov. 2020.
 Niels C. Pedersen, Michel Perron, Michael Bannasch, Elizabeth Montgomery, Eisuke Murakami, Molly Liepnieks, and Hongwei Liu, Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis, J. Feline Med. Surg. 2019; 271–281.
 Peter J. Dickinson, Michael Bannasch, Sara M. Thomasy, Vishal D. Murthy, Karen M. Vernau, Molly Liepnieks, Elizabeth Montgomery, Kelly E. Knickelbein, Brian Murphy, Niels C. Pedersen, Antiviral treatment using the adenosine nucleoside analogue GS ‐441524 in cats with clinically diagnosed neurological feline infectious peritonitis, J. Vet. Intern. Med. 2020; 1-7.
 Niels C.Pedersen, An update on feline infectious peritonitis: Diagnostics and therapeutics, Vet. J. 2014; 133-141.
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