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The nucleoside analogue GS-441524 is a common treatment for cats with feline infectious peritonitis (FIP). In a previous study, 40 cats with FIP with effusion were treated with 15 mg/kg GS-441524 orally once daily for either 42 days or 84 days, and a 42-day treatment was as effective as the earlier recommended 84-day treatment. The aim of the present study was to describe unexpected clinical and laboratory observations occurring during and after treatment (within one year) in these cats and to compare them regarding the different treatment durations. Thirty-eight cats recovered rapidly during treatment, two cats had to be euthanized, and one cat was lost to follow-up. During treatment, 25 cats developed diarrhea. Lymphocytosis occurred in 26/40 cats during treatment, eosinophilia in 25/40 during treatment, increased alanine aminotransferase activity in 22/40, alkaline phosphatase activity in 7/40, and symmetric dimethylarginine levels in 25/40. These unexpected observations occurred equally in both treatment duration groups, but statistically significantly more cats developed lymphocytosis and eosinophilia when treated for 84 days. Although most of the unexpected observations during GS-441524 treatment improved or disappeared after treatment termination, these conditions have to be monitored, and treatment should not be given for longer than necessary.

Feline infectious peritonitis (FIP) is caused by infection with the feline coronavirus (FCoV) and is fatal if left untreated. In most cats, FCoV primarily infects the gastrointestinal tract and remains asymptomatic or causes only mild enteritis, with only a small proportion of infected cats developing FIP. An excessive and harmful immune response leading to characteristic (pyo)granulomatous phlebitis is believed to play a key role in the development of FIP, along with complex interactions between host and viral factors. Our research group recently demonstrated successful treatment of cats with naturally occurring FIP using the antiviral nucleoside analogue GS-441524. Treatment led to complete recovery without any relapses for a follow-up period of one year, demonstrating both a short- and long-term cure. To investigate differential gene expression and corresponding molecular pathways in cats with FIP before, during, and after antiviral treatment, RNA sequencing was performed on full blood samples of 18 cats treated successfully in a prospective study. Samples were analyzed before treatment, at different timepoints while on treatment with GS-441524 and after completion of treatment. Additionally, gene expression profiles were compared to 12 healthy FCoV-infected control cats and 5 healthy uninfected control cats. The results revealed both a widespread dysregulation of the blood RNA signature in cats with FIP as well as its rapid normalization within the first week of treatment. Significant changes were already apparent within the first two days of treatment. The results of the present study suggest that elimination of the virus from the blood leads to rapid control and subsequent normalization of the damaging immune response, a finding that corresponds well to the clinical response to treatment. This study illustrates the host response to treatment at the molecular level and provides further evidence that a shorter treatment duration than the 84 days predominantly practiced is sufficient.

Feline infectious peritonitis (FIP) is a fatal but now treatable disease in cats caused by feline coronavirus (FCoV). This study prospectively investigated viral coinfections in 100 cats diagnosed with FIP and subsequently treated with oral GS-441524 (Bova UK) and their influence on outcome, focusing on viruses potentially associated with feline chronic gingivostomatitis (FCGS). Cats were tested for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline calicivirus (FCV), feline herpesvirus (FHV), feline foamy virus (FFV), and feline gammaherpesvirus (FcaGHV1). Coinfections were identified at the following frequencies: FCV (27), FFV (22), FHV (6), FIV (4), FcaGHV1 (2), and FeLV (2, both progressive infections). FFV infection was significantly associated with FIV (pF = 0.0021) and FHV (pF = 0.0226) infection. FCGS was present in 25/97 cats with FCV infection being associated with FCGS (pF = 0.0032); no significant associa-tions were found for the other viruses and FCGS. The 42-day oral GS-441524 treatment’s success rate was 94% (five cats died, one relapsed). Coinfections did not significantly influence disease severity or treatment outcome, although the low number of cases for some pathogens warrants further investigation. However, advanced age was associated with treatment failure, potentially due to delayed diagnosis as FIP is considered to be less common in older individuals, or to age-related changes in immune function. In summary, viral coinfections, particularly with FCV, were common and should be considered in the clinical and hygienic management of cats with FIP.

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a fatal disease in cats characterized by variable manifestations. Myocarditis represents a less commonly described pathology within the clinical spectrum of FIP. No research has described the successful treatment of FIP-induced myocarditis. In this study, 40 cats were included and treated with 15 mg/kg of GS-441524 every 24 h orally. All cats were diagnosed with FIP by reverse transcription quantitative PCR in effusion in combination with typical clinical and laboratory changes. Echocardiography was performed in all cats, and myocarditis was suspected in 4/40 cats. Equivocal wall thickness was diagnosed in 2/4 cats, while systolic dysfunction with biatrial dilation was diagnosed in the other 2/4 cats. One cat also presented with ventricular ectopy. A severe increase in cardiac troponin I was seen in all four cats (median 1.82 ng/mL (1.20–5.84 ng/mL)). Cardiac dimensions and electrocardiographic abnormalities completely normalized in all four cats during treatment with GS-441524 and remained stable after treatment discontinuation during a one-year follow-up period. Myocarditis can be a clinical feature of FIP and present with different cardiologic manifestations. FIP-induced myocarditis can be cured with GS-441524 in combination with symptomatic cardiovascular treatment including pimobendan, clopidogrel, furosemide, or atenolol, depending on the clinical presentation.

As previously demonstrated by our research group, the oral multicomponent drug Xraphconn® containing GS-441524 was effective at curing otherwise fatal feline infectious peritonitis (FIP) in 18 feline coronavirus (FCoV)-infected cats. The aims of the current study were to investigate, using samples from the same animals as in the previous study, (1) the effect of treatment on fecal viral RNA shedding; (2) the presence of spike gene mutations in different body compartments of these cats; and (3) viral RNA shedding, presence of spike gene mutations, and anti-FCoV antibody titers in samples of 12 companion cats cohabitating with the treated cats. Eleven of the eighteen treated FIP cats (61%) were shedding FCoV RNA in feces within the first three days after treatment initiation, but all of them tested negative by day 6. In one of these cats, fecal shedding reoccurred on day 83. Two cats initially negative in feces were transiently positive 1–4 weeks into the study. The remaining five cats never shed FCoV. Viral RNA loads in feces decreased with time comparable with those in blood and effusion. Specific spike gene mutations linked to systemic FCoV spread were consistently found in blood and effusion from treated FIP cats, but not in feces from treated or companion cats. A new mutation that led to a not yet described amino acid change was identified, indicating that further mutations may be involved in the development of FIP. Eight of the twelve companion cats shed FCoV in feces. All but one of the twelve companion cats had anti-FCoV antibodies. Oral treatment with GS-441524 effectively decreased viral RNA loads in feces, blood, and effusion in cats with FIP. Nonetheless, re-shedding can most likely occur if cats are re-exposed to FCoV by their companion cats.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

Until recently, the diagnosis of feline infectious peritonitis (FIP) in cats usually led to euthanasia, but recent research has revealed that antiviral drugs, including the nucleoside analog GS-441524, have the potential to effectively cure FIP. Alpha-1-acid glycoprotein (AGP) has been suggested as a diagnostic marker for FIP. However, AGP quantification methods are not easily accessible. This study aimed to establish a Spatial Proximity Analyte Reagent Capture Luminescence (SPARCLTM) assay on the VetBio-1 analyzer to determine the AGP concentrations in feline serum and effusion samples. Linearity was found in serial dilutions between 1:2000 and 1:32,000; the intra-run and inter-run precision was <5% and <15%, respectively; and AGP was stable in serum stored for at least 8 days at room temperature, at 4 °C and at −20 °C. Cats with confirmed FIP had significantly higher serum AGP concentrations (median: 2954 µg/mL (range: 200–5861 µg/mL)) than those with other inflammatory diseases (median: 1734 µg/mL (305–3449 µg/mL)) and clinically healthy cats (median 235 µg/mL (range: 78–616 µg/mL); pKW < 0.0001). The AGP concentrations were significantly higher in the effusions from cats with FIP than in those from diseased cats without FIP (pMWU < 0.0001). The AGP concentrations in the serum of cats with FIP undergoing GS-441524 treatment showed a significant drop within the first seven days of treatment and reached normal levels after ~14 days. In conclusion, the VetBio-1 SPARCLTM assay offers a precise, fast and cost-effective method to measure the AGP concentrations in serum and effusion samples of feline patients. The monitoring of the AGP concentration throughout FIP treatment provides a valuable marker to evaluate the treatment’s effectiveness and identify potential relapses at an early stage.

This is the first report on a clinical follow-up and postmortem examination of a cat that had been cured of feline infectious peritonitis (FIP) with ocular manifestation by successful treatment with an oral multicomponent drug containing GS-441524. The cat was 6 months old when clinical signs (recurrent fever, lethargy, lack of appetite, and fulminant anterior uveitis) appeared. FIP was diagnosed by ocular tissue immunohistochemistry after enucleation of the affected eye. The cat was a participant in a FIP treatment study, which was published recently. However, 240 days after leaving the clinic healthy, and 164 days after the end of the 84 days of treatment, the cured cat died in a road traffic accident. Upon full postmortem examination, including histopathology and immunohistochemistry, there were no residual FIP lesions observed apart from a generalized lymphadenopathy due to massive lymphoid hyperplasia. Neither feline coronavirus (FCoV) RNA nor FCoV antigen were identified by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry, respectively, in any tissues or body fluids, including feces. These results prove that oral treatment with GS-441524 leads to the cure of FIP-associated changes and the elimination of FCoV from all tissues.