Search Results (88)

Background: The minimized pan-coronavirus (CoV) vaccine-1 developed by our laboratory contained pDNA sequences of feline coronavirus serotype-1 (FCoV1) and SARS-CoV2 (SCoV2) spike B-cell epitopes plus FCoV/SCoV2-conserved, CoV-specific polymerase cytotoxic T-lymphocyte (CTL) epitopes formulated in lipid nanoparticle (LNP). Only FCoV2 infects feline cell lines needed for developing native challenge inoculum that causes feline infectious peritonitis (FIP). Hence, Pilot Study 1 evaluated the therapeutic efficacy and safety of the pan-CoV vaccine-1 in feline immunodeficiency virus (FIV)-infected cats, with or without FCoV1 coinfection. Pilot Study 2 evaluated the cross-protective effect of pan-CoV vaccines in specific-pathogen-free (SPF) cats against intranasal challenge with FIP virus serotype 2 (FIPV2). Methods: In Study 1, we vaccinated two FIV-infected cats (one negative and another positive for FCoV1 coinfection) intramuscularly twice with CTL epitopes-LNP vaccine and later twice with pan-CoV vaccine-1. Controls included two unvaccinated FIV-infected cats with or without FCoV1 coinfection. Study 2 assessed the sequential vaccinations of three pan-CoV vaccines in four SPF cats. The first two vaccinations were with pan-CoV vaccine-2, followed by pan-CoV vaccine-3 (twice), and lastly with pan-CoV vaccine-1 (once). Three SPF controls included two cats immunized with LNP and one lacking any immunization. Pan-CoV vaccine-2 contained pDNAs with modified FCoV1/SCoV2 B-cell epitopes plus CTL epitopes in LNP. Pan-CoV vaccine-3 contained only pDNAs with FCoV1 B-cell epitopes plus CTL epitopes in LNP. Results: Study 1 demonstrated no adverse effect with 25 μg and 50 μg CTL epitopes-LNP vaccine and 50 μg pan-CoV vaccine-1. However, 100 μg pan-CoV vaccine-1 caused fever 24 h later, which was resolved by a single Meloxicam treatment. Both vaccinees developed cross-FCoV2 neutralizing antibodies (XNAbs), immunoblot binding antibodies (bAbs) to FCoV1 receptor-binding domain (RBD), and T-cell responses to FCoV1 RBD, whereas one vaccinee also developed bAbs to SCoV2 RBD. Study 2 demonstrated no adverse effects after each vaccination. Three vaccinees developed low-titer XNAbs and bAbs to FCoV2 spike-2 by the fourth vaccination. Upon challenge, all cats developed FCoV2 NAbs and bAbs to FCoV2 nucleocapsid and RBD. High vaccine-induced T-cell responses to FCoV1 RBD and T-cell mitogen responses declined with an increase in responses to FCoV2 RBD at three weeks post-challenge. Two of the three controls died from FIP, whereas one vaccinee, with the lowest vaccine-induced immunity, died from skin vasculitis lesions and detection of FIPV2 infection by semi-nested RT-snPCR in feces. Conclusions: In Pilot Study 1, the pan-CoV vaccine-LNP dose of 50 μg had no adverse effects, but adverse effects were observed at 100 μg dose. In Pilot Study 2, the FCoV1-based B-cell vaccine(s) induced low levels of XNAbs against FIPV2 and delayed challenge infection against high-dose FIPV2. The high-dose FIPV2 infections in the vaccinated and control cats started to clear, by single housing at 23–26 weeks post-challenge, whereas two cats in Pilot Study 1 cleared natural FCoV1 transmission by 26 weeks post-infection. Full article

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 (p_F = 0.0021) and FHV (p_F = 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. Full article

Feline infectious peritonitis (FIP) is a progressive and often fatal disease caused by a virulent biotype of feline coronavirus (FCoV). Although antiviral treatments are now available, relapse and resistance remain ongoing concerns. This study investigates the therapeutic potential of P. indusiatus, a medicinal mushroom, for its antiviral and anti-inflammatory activities against FIP. The main protease (FIPV M^pro) of feline infectious peritonitis virus (FIPV) was recombinantly expressed and purified to facilitate enzyme inhibition screening. P. indusiatus exhibited the strongest FIPV M^pro inhibitory activity among the 17 mushroom extracts tested (69.2%), showing a notable level of inhibition relative to standard antiviral agents such as lopinavir and ritonavir. To assess its anti-inflammatory potential, PBMCs derived from healthy cats and FIP-associated effusions (FIP fluid) were cultured and stimulated with LPS to induce inflammation. In healthy PBMCs, P. indusiatus significantly reduced nitrite levels, with effects similar to dexamethasone. However, PBMCs from FIP fluid, already in an activated state, showed no additional response. Notably, this study is the first to successfully isolate and culture PBMCs from FIP fluid, providing a new platform for future immunological research. These findings suggest that P. indusiatus possesses both antiviral and anti-inflammatory properties, positioning it as a potential dual-action therapeutic candidate for FIP. Further investigation into cytokine signaling pathways is warranted to clarify its mechanisms of action and advance future therapeutic development. Full article

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. Full article

Feline infectious peritonitis (FIP) is a severe viral disease with a very high fatality rate. GS-441524 is an adenosine analogue that acts as an antiviral and has shown promise in FIP treatment. However, its commercialization in some regions is not yet authorized. To evaluate the efficacy of GS-441524 based on the published literature, a systematic review was conducted. This systematic review was conducted using PubMed, ScienceDirect, and Google Scholar for studies published from 2018 onwards. Following PRISMA guidelines, 11 studies (totaling 650 FIP cases treated with GS-441524 alone or in combination) were included. Therapeutic efficacy was assessed by FIP form, clinical signs, and dosage. The overall treatment success rate was 84.6%. This rate was higher when GS-441524 was combined with other antivirals and lower in cases of wet FIP or those with neurological complications. Combination therapy with other antivirals may improve outcomes in complicated FIP cases, although further studies are needed. The GS-441524 dosages associated with the best outcomes were 5–10 mg/kg once daily (or equivalent subcutaneous dose), adjusted for FIP type, severity, and presence of neurological/ocular signs. Higher dosages can be used for severe cases or to prevent relapse, but splitting into twice-daily dosing may be necessary to avoid absorption issues. In summary, this synthesis indicates that GS-441524 is a highly promising treatment for FIP, with a high success rate among treated cases. Nevertheless, randomized controlled trials are needed to establish evidence-based therapeutic protocols tailored to different FIP presentations. Full article

Feline coronavirus (FCoV) is a major pathogen causing feline infectious peritonitis (FIP), a lethal disease in cats, necessitating accurate diagnostic methods. This study developed and compared novel primers targeting the FCoV membrane (M) gene for enhanced detection. Specific primers were designed for the M gene and their performance evaluated using reverse transcription-PCR (RT-PCR), nested RT-PCR, and reverse transcription-quantitative PCR (RT-qPCR) on 80 clinical effusion samples from cats suspected of FIP. Specificity of assays was tested against other feline viruses, with sensitivity being assessed via serial dilutions of FCoV RNA. RT-qPCR had the highest sensitivity, detecting 9.14 × 10¹ copies/µL, identifying 93.75% of positive samples, followed by nested RT-PCR (87.50%, 9.14 × 10⁴ copies/µL) and RT-PCR (61.25%, 9.14 × 10⁶ copies/µL). All assays had 100% specificity, with no cross-reactivity to other viruses. The nested RT-PCR and RT-qPCR outperformed RT-PCR significantly, with comparable diagnostic accuracy. The novel primers targeting the FCoV M gene, coupled with RT-qPCR, delivered unparalleled sensitivity and robust reliability for detecting FCoV in clinical settings. Nested RT-PCR was equally precise and amplified diagnostic confidence with its high performance. These cutting-edge assays should revolutionize FCoV detection, offering trusted tools that seamlessly integrate into veterinary practice, empowering clinicians to manage feline infectious peritonitis with unprecedented accuracy and speed. Full article

Background: Feline infectious peritonitis (FIP) is a complex and devastating viral disease in cats caused by feline coronavirus (FCoV). While FCoV is commonly encountered and typically innocuous, the emergence of a mutated variant can lead to the development of FIP, a severe and often fatal condition. Method and Results: This review article provides a comprehensive overview of the etiological factors, epidemiology, clinical manifestations, and challenges associated with FIP. Additionally, it underscores the critical need for further research to enhance diagnostic capabilities and develop effective therapeutic interventions. Conclusion: By shedding light on the intricate dynamics of FIP, this review paper aims to contribute to a deeper understanding of the disease via fostering therapeutic advancements that can improve outcomes for afflicted felines. Full article

Antiviral drugs like EIDD-2801 (molnupiravir; MPV) have been successfully used in the treatment of feline infectious peritonitis (FIP). The previous study of the pharmacokinetics of MPV in healthy cats showed promise for its use and safety. The objective was to determine the pharmacokinetics of molnupiravir in cats with naturally occurring FIP by measuring MPV and EIDD-193 (β-D-N4-hydroxycytidine; NHC) serum levels. Blood was collected from seven cats diagnosed with naturally occurring FIP treated at 1, 2, 4, 6 and 12 h post oral MPV administration and at 12 h post pill administration 7 days later. Serum concentrations of MPV and NHC were determined using a previously published high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method. The mean dose of MPV was 15.44 mg/kg (SD ± 1.82). The mean peak serum concentration of MPV (C_max) after a single PO dose of MPV was 38 ng/mL (SD ± 5). The mean peak serum concentration of NHC (C_max) after a single PO dose of MVP was 1551 ng/mL (SD ± 720). the time to reach NHC C_max (T_max) was 2.6 h (SD ± 1.4), and the NHC elimination half-life was 1.6 h (SD ± 1.1). Minimal drug accumulation was seen in trough concentrations following twice-daily dosing for 7 days. The low MPV levels may be explained by fast conversion to its active metabolite NHC. The mean NHC concentrations at all time points were at least 4 times the reported in vitro IC₅₀ for feline coronavirus strains and twice-daily dosing for seven days did not lead to drug accumulation within the serum. The results support the use of MPV in the treatment of FIP, and if therapeutic drug monitoring is to be performed, NHC should be measured. Full article

Feline infectious peritonitis (FIP) is caused by mutated feline coronaviruses. Immune-mediated hemolytic anemia (IMHA) arises due to immune-mediated erythrocyte destruction and can be non-associative or associative with diseases such as FIP. Records of cats with FIP were reviewed to find those with associative IMHA based on exclusion of other causes of anemia and a positive saline agglutination test and/or Coombs test. The inclusion criteria were met for 45 cats (26 (58%) cats with effusive and 19 (42%) with non-effusive FIP). Median hematocrit was 18% (interquartile range [IQR] 13–20). Anemia was non-regenerative in 36 (80%) cats and regenerative in 5 (11%) cats; 4 (9%) cats had no reticulocyte count available. Concurrent thrombocytopenia was present in 18 (40%) cats. All 45 cats were treated with nucleoside analogs, and 44 (98%) cats with glucocorticoids; in 5 (11%) cats, glucocorticoids were added after starting antiviral treatment due to persistent anemia. Median follow-up was 72 days (IQR 14–246); at the time of last follow-up 33 (73%) cats had survived while 12 (27%) had died or were euthanized. Of the 33 surviving cats, 17 achieved remission of both FIP and IMHA. In three cats, FIP remission was achieved, but IMHA relapsed; in one of these, IMHA relapsed twice. FIP relapsed without IMHA in two cats, and both FIP and IMHA relapsed in one cat. In 9 cats the antiviral and glucocorticoid treatment is still ongoing at the time of the publication. Although FIP is likely an uncommon cause of associative IMHA, as more cats with FIP are treated with antiviral therapy, it is important to consider IMHA as a possible cause of anemia in cats with FIP. Full article

Feline coronavirus (FCoV), the causative agent behind feline infectious peritonitis (FIP), is one of the biggest infectious threats to feline health. Despite this threat, the tissue distribution and viral RNA levels in cats infected with feline coronaviruses are poorly understood in the context of natural infection. Here, we used a two-step reverse-transcription quantitative PCR (RT-qPCR) to examine viral RNA levels from different sampling sites in both cats that have been clinically suspected of FIP and their feline housemates. We show that the distribution and amount of FCoV viral RNA does not differ between FCoV-infected cats with FIP and their feline housemates in blood, conjunctiva, or feces. Furthermore, in all FIP and non-FIP cases, viral RNA levels were higher in fecal samples than the blood. Taken together, these results show that amount of viral RNA does not differ between FCoV-infected cats with FIP and their healthy housemates in several sample types. Our results indicate a need for closer examination of FCoV pathogenesis independent of viral dissemination, including an assessment of intrahost evolution of FCoVs and FCoVs’ interactions with the feline immune system. Full article

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. Full article

Feline Infectious Peritonitis (FIP) is caused by a systemic feline coronavirus (FCoV). Prior to June 2024, compounded FIP treatment was unavailable for prescription by veterinarians in the United States, leading to many cat owners obtaining treatment through unlicensed “black market” sources. We hypothesized that clinicopathologic data could provide insight on prognostic indicators for the treatment of FIP with GS-441524. This study used data gathered via surveys from 126 cat owners who used “black market” GS-441524 for their cats. We compared bloodwork parameters over twelve weeks of treatment. None of the clinicopathologic correlates, when analyzed via two-sample t-tests, produced statistically significant results between cured, deceased, and relapsed groups. Within cats considered cured, it was observed that hematocrit (HCT) and white blood cell (WBC) values were within normal limits by the 2–6-week period. Cats who died during the study had lower HCT and higher WBC values within the 2–6-week period. Trends were also seen in A/G and total bilirubin (T-BIL), with deceased patients showing a higher A/G ratio and lower value than those in the cured group. Overall, these data demonstrate a lack of traditional clinicopathologic parameters which are consistently predictive of FIP therapy success. Other predictors of outcome with antiviral therapy should be pursued. Full article

Case summary: A 2-year-old male neutered domestic shorthair cat was presented with a progressive history of tetraparesis, ataxia, and inappetence over 4 days. A physical exam revealed mucopurulent nasal discharge and stertor. A neurologic exam revealed a multifocal neurolocalization. The cat was non-ambulatory tetraparetic and developed seizures while in hospital. Hematologic assessment revealed anemia, hypoalbuminemia and hyperglobulinemia. Magnetic resonance imaging (MRI) of the brain revealed multifocal meningeal contrast enhancement in the brainstem and cervical spine, as well as mandibular and retropharyngeal lymphadenopathy. Cerebrospinal fluid revealed marked neutrophilic pleocytosis; no infectious organisms were seen. Toxoplasma IgG/IgM and Cryptococcus antigen latex agglutination were negative. Mandibular and abdominal lymph nodes were aspirated, and cytology revealed mixed inflammation. The cat was suspected to have feline infectious peritonitis, and to aid in clinical diagnosis he was enrolled in research study—with targeted Nanopore-based sequencing specifically identifying and characterizing FCoV-1 RNA in spinal fluid and anal swab, but not in urine. The cat was treated with anticonvulsants (phenobarbital and levetiracetam), an antibiotic (ampicillin/clavulanic acid), and GS-441524. Neurologic signs did not improve on an antibiotic alone but improved significantly after two subcutaneous injections of GS-441524. The cat received an 84-day course of GS-441524 and, at the time of manuscript preparation (over 12 months after diagnosis), remains ambulatory and seizure-free without recurrence of neurologic signs and no detectable viral shedding in feces. Full article

Feline infectious peritonitis (FIP), a devastating disease with near-complete mortality, is caused by the feline coronavirus (FCoV) and affects domestic cats worldwide. Herein, we report the development of a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay incorporating xylenol orange (XO) as a visual indicator for FCoV detection. The assay employed six oligonucleotide primers targeting regions of the nucleocapsid (N) gene. Under optimized conditions (65 °C, 60 min), amplification products were detected through pH-dependent colour changes in the XO dye. The RT-LAMP-XO assay exhibited high specificity for FCoV, with no cross-reactivity against other common feline viral pathogens. While the detection limit (1.7 × 10¹ copies/µL) was an order of magnitude higher than that of qPCR, the method offered advantages in simplicity and speed compared to existing diagnostic approaches. Although less sensitive than qPCR, the RT-LAMP-XO assay may serve as a rapid screening tool when used in combination with additional primer sets. These findings demonstrate the potential utility of XO-based RT-LAMP as a simple, visual detection method for FCoV infection. Full article

Background/Objectives: Feline coronavirus (FCoV) belongs to the family Coronaviridae and includes two pathotypes, the less virulent feline enteric coronavirus (FECV), which replicates in the enteric epithelial cells, and feline infectious peritonitis virus (FIPV), which is more virulent, replicates efficiently within monocytes/macrophages with systemic involvement and may cause feline infectious peritonitis (FIP), a progressive and often fatal disease. The diagnosis of FIP is complex and requires different examinations. Among serological tests, the indirect immunofluorescent antibody test (IFAT), considered the gold standard, and the enzyme-linked immunosorbent assay (ELISA) are the most widely used to detect FCoV antibodies. The aim of this work was the development of FCoVCHECK Ab ELISA, a new rapid indirect test for the detection of FCoV antibodies in feline serum/plasma samples. Methods: FCoVCHECK Ab ELISA was developed after a meticulous set-up and cut-off analysis through several methods, including the Youden’s index and ROC curve, to achieve the best test performance. It was validated by testing 110 feline sera (62 positives and 48 negatives) against the reference IFAT and compared with two other rapid ELISA tests, INgezim Corona Felino (Gold Standard Diagnostics) and ImmunoComb Feline Coronavirus (FCoV) [FIP] Antibody Test Kit (Biogal). Conclusions: FCoVCHECK Ab ELISA agreed with IFAT at 96.4% (93.5% sensitivity, 95% confidence interval (CI): 83.5–97.9%; 100% specificity, 95% CI: 90.8–100%), with ImmunoComb FCoV at 93.6% and with INgezim Corona Felino at 82.7%. Intra- and inter-assay accuracy and precision gave coefficients of variation lower than 20%. Compared to IFAT, the new assay correctly identifies positive and negative samples with a good correlation, and, in addition, it is simpler, faster and provides a less subjective reading of the results. Full article