Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.

Curing Cats with Feline Infectious Peritonitis with an Oral Multi-Component Drug Containing GS-441524.

Case series summary This case series describes three shelter-housed cats concurrently diagnosed with feline infectious peritonitis (FIP). The cats were from a cohort of seven surrendered from the site of a house fire. The three cats presented with mild upper respiratory signs. Within 10 days they clinically declined: progressive signs included pyrexia, icterus, lethargy, anorexia and cavitary effusions. Necropsy followed by histopathology and immunohistochemistry confirmed a diagnosis of FIP in all three. Molecular analysis of the causative feline coronavirus (FCoV) revealed varied amino acid alterations in the spike gene both between cats and between sample types in individual cats. A fourth cat from the cohort remained healthy in the shelter but succumbed to FIP 6 weeks post-adoption. Relevance and novel information This case series places FCoV genetic sequences in the context of clinical signs in a small shelter outbreak. Each of the three cats concurrently developed a slightly different clinical presentation. PCR amplification and genetic sequencing revealed that two cats shared an S1/S2 cleavage site mutation (R790S) previously described to be associated with the development of FIP; one of the cats had an additional S1/S2 cleavage site mutation (R793S). The third cat had a single, identical S1/S2 point mutation (R790G) unique from the other two cats; the R790G mutation has not been previously reported. This case series provides interesting data on point mutations associated with the development of FIP and provides support for a ‘circulating virulent–avirulent theory’ of FIP pathogenesis in a small shelter outbreak.

https://journals.sagepub.com/doi/pdf/10.1177/20551169221074226

Outbreak of feline infectious peritonitis (FIP) in shelter-housed cats: molecular analysis of the feline coronavirus S1/S2 cleavage site consistent with a ‘circulating virulent–avirulent theory’ of FIP pathogenesis

Feline infectious peritonitis (FIP) is one of the most important infectious diseases and causes of death in cats; young cats less than 2 years of age are especially vulnerable. FIP is caused by a feline coronavirus (FCoV). It has been estimated that around 0.3% to 1.4% of feline deaths at veterinary institutions are caused by FIP.This document has been developed by a Task Force of experts in feline clinical medicine as the 2022 AAFP/EveryCat Feline Infectious Peritonitis Diagnosis Guidelines to provide veterinarians with essential information to aid their ability to recognize cats presenting with FIP.Nearly every small animal veterinary practitioner will see cases. FIP can be challenging to diagnose owing to the lack of pathognomonic clinical signs or laboratory changes, especially when no effusion is present. A good understanding of each diagnostic test's sensitivity, specificity, predictive value, likelihood ratio and diagnostic accuracy is important when building a case for FIP. Before proceeding with any diagnostic test or commercial laboratory profile, the clinician should be able to answer the questions of 'why this test?' and 'what do the results mean?' Ultimately, the approach to diagnosing FIP must be tailored to the specific presentation of the individual cat.Given that the disease is fatal when untreated, the ability to obtain a correct diagnosis is critical. The clinician must consider the individual patient's history, signalment and comprehensive physical examination findings when selecting diagnostic tests and sample types in order to build the index of suspicion 'brick by brick'. Research has demonstrated efficacy of new antivirals in FIP treatment, but these products are not legally available in many countries at this time. The Task Force encourages veterinarians to review the literature and stay informed on clinical trials and new drug approvals. 

2022 AAFP/EveryCat Feline Infectious Peritonitis Diagnosis Guidelines

Feline coronaviruses (FCoV) are common viral pathogens of cats. They usually induce asymptomatic infections but some FCoV strains, named Feline Infectious Peritonitis Viruses (FIPV) lead to a systematic fatal disease, the feline infectious peritonitis (FIP). While no treatments are approved as of yet, numerous studies have been explored with the hope to develop therapeutic compounds. In recent years, two novel molecules (GS-441524 and GC376) have raised hopes given the encouraging results, but some concerns about the use of these molecules persist, such as the fear of the emergence of viral escape mutants or the difficult tissue distribution of these antivirals in certain affected organs. This review will summarize current findings and leads in the development of antiviral therapy against FCoV both in vitro and in vivo, with the description of their mechanisms of action when known. It highlights the molecules, which could have a broader effect on different coronaviruses. In the context of the SARS-CoV-2 pandemic, the development of antivirals is an urgent need and FIP could be a valuable model to help this research area.

Feline Coronavirus Antivirals: A Review.

Feline calicivirus (FCV) is a common cat virus causing clinical signs such as oral ulcerations, fever, reduced general condition, pneumonia, limping and occasionally virulent-systemic disease. Efficacious FCV vaccines protect against severe disease but not against infection. FCV is a highly mutagenic RNA virus whose high genetic diversity poses a challenge in vaccine design. The use of only one modified-live FCV strain over several decades might have driven the viral evolution towards more vaccine-resistant variants. The present study investigated the clinical signs, duration, and amount of FCV shedding, RNAemia, haematological changes and acute phase protein reaction in SPF cats after subcutaneous modified-live single strain FCV vaccination or placebo injection and two subsequent oronasal heterologous FCV challenge infections with two different field strains. Neither clinical signs nor FCV shedding from the oropharynx and FCV RNAemia were detected after vaccination. After the first experimental infection, vaccinated cats had significantly lower clinical scores, less increased body temperature and lower acute phase protein levels than control cats. The viral RNA loads from the oropharynx and duration and amount of RNAemia were significantly lower in the vaccinated animals. No clinical signs were observed in any of the cats after the second experimental infection. In conclusion, FCV vaccination was beneficial for protecting cats from severe clinical signs, reducing viral loads and inflammation after FCV challenge.

https://www.mdpi.com/1999-4915/13/8/1505/pdf

Modified-Live Feline Calicivirus Vaccination Reduces Viral RNA Loads, Duration of RNAemia, and the Severity of Clinical Signs after Heterologous Feline Calicivirus Challenge

Feline infectious peritonitis (FIP) is a systemic, potentially fatal viral disease. The objectives of this study were to review clinical and laboratory features and treatment of cats highly suspected of FIP in Wuhan, China. The clinical records of 127 cats highly suspected of FIP were reviewed for history, clinical signs, physical findings, and diagnostic test results. Sex, neutering status, breed, age, and month of onset of disease were compared with the characteristics of the clinic population. Age and neutering status were significantly correlated with FIP-suspicion. Sex, breed and onset month were not associated with FIP. There were many more FIP-suspected cases in cats in young cats or male intact cats. Effusion was observed in 85.8% of the FIP-suspected cats. Increased serum amyloid A (SAA) and lymphopenia were common laboratory abnormalities in the FIP cases. Furthermore, 91.7% of the cats highly suspected of FIP had an albumin/globulin (A/G) ratio < 0.6, while 85.3% had an A/G ratio < 0.5. The mortality rate for FIP-suspected cats was 67%, and six submitted cases were confirmed by FIP-specific immunohistochemistry. Of the 30 cats treated with GS-441524 and/or GC376, 29 were clinically cured. The study highlights the diverse range of clinical manifestations by clinicians in diagnosing this potentially fatal disease. A/G ratio and SAA were of higher diagnostic value. GS-441524 and GC376 were efficient for the treatment of FIP-suspected cats.

/pdf/a-retrospective-study-of-clinical-and-laboratory-features-3xnopjsoim.pdf

Xiaoya Liu

Papers

A retrospective study of clinical and laboratory features and treatment on cats highly suspected of feline infectious peritonitis in Wuhan, China.