OBJECTIVE: This nationwide study aimed to investigate risk factors associated with FIP and determine optimal sample submission strategies for its diagnosis.
METHODS: A total of 14,035 clinical samples from cats across the US were analyzed by means of reverse transcriptase quantitative PCR to detect replicating feline coronavirus (FCoV). χ2 and logistic regression analyses were conducted to assess the association between FCoV detection rates and risk factors such as age, gender, breed, and types of submitted samples.
RESULTS: Higher FCoV detection rates were observed in younger cats, particularly those aged 0 to 1 year, and in male cats. Purebred cats, notably British Shorthairs [OR: 2.81; P < .001], showed a higher incidence of FCoV infection than other cats. Peritoneal fluid (OR, 7.51; P < .001) exhibited higher FCoV detection rates than other samples, while lower rates were seen in blood samples (OR, 0.08; P < .001) than in other samples. High FCoV detection rates were found in urine, kidney, and lymph node samples.
CONCLUSIONS: The study identified significant risk factors associated with FIP. Optimal sample submission strategies, particularly emphasizing the use of peritoneal fluid, kidney, and lymph node, were identified to improve FIP detection rates. Urine yielded a relatively high frequency of infection and viral loads compared with most other samples.
CONCLUSIONS: Understanding the risk factors and optimizing sample selection for FIP diagnosis can aid in the early detection and management of the disease, ultimately improving outcomes for affected cats. These findings contribute valuable insights to FIP epidemiology and underscore the importance of continued research to enhance diagnostic strategies and disease management approaches.

Coronaviruses are widespread in mammals and birds, causing mostly digestive and respiratory problems. In cats, feline coronaviruses undergo mutations while replicating, giving rise to the fatal coronavirus causing the feline infectious peritonitis (FIP) disease. Several mutations in viral genes, among them 3c and M, are involved in the development of FIP. In order to study these viral shifts, samples of 43 organs, feces, and ascites collected from cats showing clinical signs of feline infectious peritonitis were tested, and the sequences obtained for the 3c and M genes were analyzed. The 3c gene nucleotides showed truncations commonly observed in feline infectious peritonitis virus. Additionally, the sequences corresponding to the 3c genes obtained from different organs of the same individual displayed high similarities, supporting the internal mutation theory. The analyses of the M gene and putative polypeptides showed similarities with canine coronaviruses, supporting the recombination theory between feline and canine coronaviruses. Infectious coronaviral strains are still challenging because of the difficulty in obtaining an effective vaccine for their prevention, and also because of the limited alternatives for therapy of FIP in cats.

Although not registered for feline infectious peritonitis (FIP) in Japan, nucleoside analogs have shown efficacy and we have been offering them to owners of cats with FIP at our clinic since January 2020. The aim of this study was to investigate outcomes in cats with FIP who received GS-441524 or molnupiravir. Diagnosis of FIP was based on clinical signs, laboratory test results, and the presence of feline coronavirus RNA in blood or effusion aspirate. After providing verbal and written information, owners of cats with a presumptive diagnosis of FIP with a were offered antiviral treatment with commercially sourced GS-441524 from June 2020, and either GS-441524 or compounded molnupiravir from January 2022. Dosing was 12.5-25 mg/kg/day for GS-441524 and 20-40 mg/kg/day for molnupiravir, depending on the presence of effusion and neurological and/or ocular signs, and continued for 84 days. Overall, 118 cats with FIP (effusive in 76) received treatment, 59 with GS-4421524 and 59 with molnupiravir. Twenty cats died, 12/59 (20.3%) in the GS-441524 group and 8/59 (13.6%) in the molnupiravir group (p = 0.326), with most deaths within the first 10 days of starting treatment. Among survivors, neurological and ocular signs resolved in all but one cat, who had persistent seizures. Of the cats completing treatment, 48/48 in the GS-441524 group and 51/52 in the molnupiravir group achieved remission. Laboratory parameters normalized within 6 to 7 weeks of starting drug administration. Adverse events, such as primarily hepatic function abnormalities, were transient and resolved without specific intervention. Our data indicate that GS-441524 and molnupiravir show similar effects and safety in cats with FIP.

Feline infectious peritonitis (FIP) is a devastating and often fatal disease caused by feline coronavirus (FCoV). Currently, there is no widely used vaccine for FIP, and many attempts using a variety of platforms have been largely unsuccessful due to the disease\'s highly complicated pathogenesis. One such complication is antibody-dependent enhancement (ADE) seen in FIP, which occurs when sub-neutralizing antibody responses to viral surface proteins paradoxically enhance disease. A novel vaccine strategy is presented here that can overcome the risk of ADE by instead using a lipid nanoparticle-encapsulated mRNA encoding the transcript for the internal structural nucleocapsid (N) FCoV protein. Both wild type and, by introduction of silent mutations, GC content-optimized mRNA vaccines targeting N were developed. mRNA durability in vitro was characterized by quantitative reverse-transcriptase PCR and protein expression by immunofluorescence assay for one week after transfection of cultured feline cells. Both mRNA durability and protein production in vitro were improved with the GC-optimized construct as compared to wild type. Immune responses were assayed by looking at N-specific humoral (by ELISA) and stimulated cytotoxic T cell (by flow cytometry) responses in a proof-of-concept mouse vaccination study. These data together demonstrate that an LNP-mRNA FIP vaccine targeting FCoV N is stable in vitro, capable of eliciting an immune response in mice, and provides justification for beginning safety and efficacy trials in 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.

Hair cortisol concentration (HCC) and a questionnaire were used as indicators of chronic stress status and quality of life (QoL), respectively, in cats. To date, there has been limited research on the simultaneous application of both indicators in unwell cats. Our aim was to evaluate HCC and questionnaire data obtained from a healthy cat cohort (n = 61) and cat cohorts with either chronic kidney disease (CKD) (n = 78) or suspected feline infectious peritonitis (FIP) (n = 24). Furthermore, we also investigated the correlation between HCC and clinical pathological data. For this study, hair from the abdomen of cats was collected and analyzed for HCC using a commercial ELISA kit. Owners also completed a questionnaire, from which average-item-weighted-impact-scores (AWISs) were calculated. Cats with late-stage-CKD (median, HCC = 330.15 pg/mg, AWIS = -0.43) presented with a significantly higher HCC (p < 0.01) and a significantly lower AWIS (p < 0.01) than cats with early-stage-CKD (HCC = 183.56 pg/mg, AWIS = 1.08). Similarly, there were significant differences in both HCC (p < 0.001) and AWIS (p < 0.001) between cats with suspected FIP (HCC = 896.27 pg/mg, AWIS = -1.97) and healthy cats (HCC = 181.24 pg/mg, AWIS = 1.24). The degree of consistency between the HCC results and the questionnaire results reminds us that the severity of a chronic disease or the presence of a life-threatening disease can significantly increase stress and thus can affect the QoL of cats.

GS-441524 is an adenosine nucleoside antiviral demonstrating significant efficacy in the treatment of feline infectious peritonitis (FIP), an otherwise fatal illness, resulting from infection with feline coronavirus. However, following the emergence of COVID-19, veterinary development was halted, and Gilead pursued clinical development of a GS-441524 pro-drug, resulting in the approval of Remdesivir under an FDA emergency use authorization. Despite lack of regulatory approval, GS-441524 is available without a prescription through various unlicensed online distributors and is commonly purchased by pet owners for the treatment of FIP. Herein, we report data obtained from the analytical characterization of two feline renal calculi, demonstrating the propensity for GS-441524 to cause renal toxicity through drug-induced crystal nephropathy in vivo. As definitive diagnosis of drug-induced crystal nephropathy requires confirmation of the lithogenic material to accurately attribute a mechanism of toxicity, renal stone composition and crystalline matrix were characterized using ultra-performance liquid chromatography photodiode array detection (UPLC-PDA), ultra-performance liquid chromatography mass spectrometry (LCMS), nuclear magnetic resonance (NMR) spectroscopy, X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). This work serves to provide the first analytical confirmation of GS-441524-induced crystal nephropathy in an effort to support toxicologic identification of adverse renal effects caused by administration of GS-441524 or any pro-drug thereof.

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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.

BACKGROUND: feline infectious peritonitis (FIP) is a fatal disease in cats classified as either effusive (\'wet\'), non-effusive (\'dry\'), or a mixture of both forms (\'mixed\'). The anti-FIP therapeutic effects of Mutian and molnupiravir, two drugs with a nucleic acid analog as an active ingredient, have been confirmed recently.
METHODS: Of the cats with FIP, we observed a total of 122 and 56 cases that achieved remission after the administration of Mutian and molnupiravir as routine treatments, respectively. Changes in clinical indicators suggested to be correlated with FIP remission (weight, hematocrit, and albumin-to-globulin ratio) before and after the administration of each drug and during follow-up observation were statistically compared for each FIP type.
RESULTS: In all three FIP types, the administration of either Mutian or molnupiravir resulted in statistically significant increases in these indicators. Furthermore, the effect of Mutian on improving the albumin-to-globulin ratio was not observed at all in wet FIP, as compared with that of molnupiravir, but statistically significant in mixed and dry (p < 0.02 and p < 0.003, respectively). The differences in albumin-to-globulin ratio were all due to those of circulating globulin levels.
CONCLUSIONS: These results indicate that slight inflammatory responses might be elicited continuously by a residual virus that persisted through molnupiravir treatments.