Sustained clinical remission and long-term safety of molnupiravir as first-line therapy for effusive feline infectious peritonitis: a 40-week retrospective study

Abstract

Feline infectious peritonitis (FIP) is a highly fatal disease caused by feline coronavirus (FCoV). Although the acute clinical efficacy of molnupiravir as first-line therapy has been recognized, there are limited data regarding the long-term durability of clinical outcomes and safety profile posttreatment. This retrospective study aimed to evaluate the acute response (weeks 0–12) and long-term clinicopathological outcomes (up to week 40) in cats with naturally occurring effusive FIP treated with molnupiravir. Forty-two cats were included. They received a median molnupiravir dose of 14.3 mg/kg twice daily for at least 84 days (12 weeks). Molnupiravir treatment rapidly resolved clinical signs and effusions (median 7 days). Moreover, significant improvements in white blood cell and neutrophil counts were observed within the first week (p < 0.05). A transient elevation in alanine aminotransferase levels occurred initially but completely normalized by week 7 without requiring treatment discontinuation. Importantly, paired analysis between posttreatment (week 12) and long-term follow-up (week 40) data revealed no significant deviations in hematological parameters (e.g., hematocrit and lymphocytes) or renal function (creatinine) (p > 0.05), indicating sustained physiological stability. In summary, molnupiravir is highly effective and safe as first-line treatment for effusive FIP. The transient nature of hepatic enzyme elevation and long-term hematological and renal stability provide strong clinical assurance for its long-term safety profile and the potential for a sustained clinical cure.

1. Background

Feline infectious peritonitis (FIP) is a highly fatal disease caused by a virulent biotype of feline coronavirus (FCoV). According to research, the incidence of FIP among cats exposed to FCoV in a multi-cat environment has been reported to be as high as 14% (Sase, 2023). Immunohistochemistry is considered as the gold standard for the definitive diagnosis of FIP. However, the acquisition of appropriate antemortem tissue samples is frequently precluded by patient instability, anesthetic risks, and financial constraints (Sase, 2023; Tasker et al., 2023; Thayer et al., 2022). Consequently, effusive FIP is routinely diagnosed presumptively in clinical practice. This diagnosis is based on a comprehensive synthesis of signalment; physical examination findings; characteristic clinicopathological abnormalities; and the detection of FCoV RNA, particularly from effusion samples, through reverse transcription polymerase chain reaction (RT-PCR) (Addie et al., 2009; Felten & Hartmann, 2019; Tasker et al., 2023; Thayer et al., 2022).

With the recent introduction of nucleoside analog antiviral drugs, the therapeutic landscape for FIP has undergone a paradigm shift (Barua et al., 2023; Coggins et al., 2023; Pedersen et al., 2019; Roy et al., 2022; Sase, 2023; Sase et al., 2024; Tasker et al., 2023; Zuzzi-Krebitz et al., 2024). Molnupiravir (an orally bioavailable ribonucleoside prodrug) has emerged as a potent therapeutic agent with broad-spectrum anti-coronaviral activity. Its active metabolite (EIDD-1931) inhibits viral replication by inducing translational mutagenesis through the disruption of the viral RNA-dependent RNA polymerase. This results in lethal mutagenesis by increasing the viral mutation rate beyond a tolerable threshold, which ultimately leads to viral inactivation. According to recent studies, molnupiravir is an effective and well-tolerated first-line antiviral therapy, achieving high rates of acute clinical remission in cats with FIP (Clark et al., 2025; Reagan et al., 2024; Roy et al., 2022; Sase, 2023; Sase et al., 2024; Yoshida et al., 2025). However, despite these promising outcomes, the long-term durability of clinical outcomes and physiological impact of the drug remain unknown. Moreover, there is a lack of comprehensive and prolonged follow-up data specifically evaluating sustained hematological stability, potential delayed hepatotoxicity or nephrotoxicity, and overall clinical outcomes well beyond the standard treatment period.

Therefore, the present study aimed to evaluate the acute response and long-term clinicopathological outcomes (up to 40 weeks) in cats with naturally occurring effusive FIP treated with molnupiravir as first-line therapy. Molnupiravir was hypothesized to not only provide a rapid and favorable clinical response, but also establish a durable clinical cure characterized by long-term physiological stability, without including chronic adverse effects, thereby confirming its safety as a definitive management option for effusive FIP.

2. Methods

2.1. Study design and ethical consideration

This study was designed as a retrospective, single-center, observational cohort analysis of cats naturally infected with effusive FIP that were presented to Prasu Arthorn Veterinary Teaching Hospital between February 2023 and June 2024. Data were extracted from the medical records. Formal ethical approval was waived by the Institutional Animal Care and Use Committee of the Faculty of Veterinary Science, Mahidol University because the study used data obtained from medical records only and did not involve any direct interaction with live animals or animal carcasses. Informed consent was obtained from all owners before the initiation of any diagnostic procedures and off-label therapeutic interventions using molnupiravir.

2.2. Case selection and diagnostic criteria

Cats that completed treatment with oral molnupiravir were eligible for inclusion. Data, including signalment (sex, age, breed, body weight, and neuter status), initial presenting clinical signs, complete blood count (CBC), serum biochemistry profiles, thoracic and abdominal radiographic findings, abdominal ultrasonography, echocardiography, initial molnupiravir dosage, and reported adverse effects, were collected. CBC analysis was performed using a hematology analyzer (BC-5300 Vet Analyzer; Mindray). Serum biochemistry profiles, including blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), alkaline phosphatase (ALP), glucose, total protein, albumin, and bilirubin, were analyzed using an automated chemistry analyzer (AU-480 Chemistry Analyzer; Beckman Coulter).

A presumptive diagnosis of effusive FIP was established based on signalment, physical examination, clinical signs, hematological and serum biochemistry abnormalities, fluid analysis, and diagnostic imaging (thoracic and abdominal radiography, abdominal ultrasonography, and echocardiography). Thoracic and abdominal radiographs were performed to assess the presence of pleural effusion and/or abdominal effusion. Meanwhile, point-of-care ultrasonography was conducted to guide thoracocentesis or abdominocentesis for therapeutic purposes and fluid sample collection, as well as to evaluate the presence of pericardial effusion. Rivalta’s test, bacterial culture, cytology, albumin-to-globulin (A/G) ratio, and RT-PCR for FCoV RNA were used to assess effusion. Abdominal ultrasonography was performed to exclude intra-abdominal neoplasia. Moreover, echocardiography was conducted to evaluate cardiac function and exclude feline cardiomyopathy.

The inclusion criteria were as follows: (a) presence of ≥2 clinical signs consistent with effusive FIP; (b) presence of pleural and/or abdominal effusion; (c) presence of ≥2 hematological and/or serum biochemistry abnormalities typical for effusive FIP (e.g., anemia, lymphopenia, neutrophilia, hyperproteinemia, hyperglobulinemia, hypoalbuminemia, hyperbilirubinemia, or serum A/G ratio <0.8); and (d) positive Rivalta’s test, negative bacterial culture, cytological findings consistent with FIP, and/or positive FCoV RNA detection by RT-PCR in effusion samples. Cats that met these criteria were presumptively diagnosed with effusive FIP.

Meanwhile, the exclusion criteria were as follows: evidence of bacterial pleuritis or peritonitis, cardiomyopathy, mediastinal lymphoma, other neoplasia, or incomplete clinical follow-up.

2.3. Therapeutic protocol and clinical monitoring

All enrolled cats received oral molnupiravir (MONOVIR; Batch No D650540; Regulation No 1A55/65 [NG]; Government Pharmaceutical Organization, Pathum Thani, Thailand) as first-line therapy. The prescribed dosage was 10–15 mg/kg twice daily. Cats weighing <2.5 kg received a dose of 33.3 mg, whereas those weighing ≥2.5 kg received a dose of 50 mg. Dosage adjustments were made during the treatment period in response to body weight changes or clinical deterioration. The minimum duration of the treatment phase was established at 84 days (12 weeks).

A standardized monitoring protocol was implemented during the active treatment phase (weeks 0–12) and posttreatment monitoring phase (weeks 12–40). Comprehensive physical examinations, along with CBC and serum biochemistry profiling, were performed at baseline (week 0) and weeks 1, 7, and 12 during the treatment phase. Diagnostic imaging (radiography and ultrasonography) was performed sequentially to monitor effusion resolution. Following treatment cessation at week 12, an extended follow-up assessment, encompassing complete physical and clinicopathological evaluations, was performed at week 40 to ascertain long-term stability and clinical cure.

Disease remission was defined as follows: (a) resolution of clinical signs associated with initial presentation; (b) lack of relapse of clinical signs after discontinuation of the study drug; (c) resolution of pleural and/or abdominal effusion; and (d) normalization of CBC and serum biochemistry parameters, including plasma protein, albumin, globulin, A/G ratio ≥0.6, and/or bilirubin levels (Clark et al., 2025; Reagan et al., 2024)(Table 1).

Table 1.

Treatment and monitoring protocol for cats with effusive form FIP receiving oral administered molnupiravir.

Treatment phase (week 0–12)
Week	Physical examination	Clinical monitoring noted	CBC and serum biochemistry	Thoracic or abdominal radiography	Abdominal ultrasonography and/or echocardiography
0	X	X	X	X	X
1	X	X	X	X
3	X	X	X	X
7	X	X	X	X
12	X	X	X	X
Monitoring phase (week 12–40)
12	X	X	X	X	X
40	X	X	X	X

2.4. Statistical analysis

Nonparametric statistical methods were used considering the nonnormal distribution of clinical data (assessed via the Shapiro–Wilk test). Descriptive statistics were presented as medians with interquartile ranges. The number of cats undergoing CBC and serum biochemistry profiling fluctuated during treatment phase (week 0, 1, 7 and 12) due to the financial constraints of owners. Consequently, total number of observations varied across specific parameters and time points based on retrospective data avaliablity (Table 6).

Table 6.

Hematological and serum biochemistry in FIP cats initial (week 0) and at week 1, 7, and 12 of treatment. Results are shown as median with interquartile ranges for non-normally distributed.

Parameter	FIP cats
	Initial treatment (week 0)	Week 1	pa	Week 7	pb	Week 12	pc
WBC (x 103/μL)	n = 38 16.10; 13.11–24.95	n = 38 13.6; 10.88–18.68	0.0148	n = 37 10.95; 8.61–14.28	0.0003	n = 37 10.92; 8.38–15.31	< 0.001
NEUT (x 103/μL)	n = 38 11.85; 9.49–18.94	n = 38 9.12; 7.01–12.62	0.0019	n = 37 7.65; 5.70–10.39	0.0001	n = 37 7.63; 5.42–9.85	< 0.001
LYMPH (x 103/μL)	n = 38 3.08; 2.57–4.45	n = 38 3.44; 2.82–4.08	0.7964	n = 37 2.85; 2.04–3.48	0.0527	n = 37 2.65; 1.86–3.21	0.0336
MONO (x 103/μL)	n = 38 0.72; 0.46–1.20	n = 39 0.45; 0.28–0.63	0.0052	n = 37 0.39; 0.31–0.59	< 0.001	n = 37 0.41; 0.20–0.65	< 0.001
PLT (x 103 cells/mm3)	n = 39 151.00; 87.50–230.00	n = 39 182.00; 128.50–288.00	0.0559	n = 38 199.50; 170.25–255.50	0.0805	n = 38 219.00; 154.00–264.80	0.0167
NLR	n = 38 3.92; 3.43–4.81	n = 38 2.84; 1.91–3.54	< 0.001	n = 37 2.96; 2.22–3.64	0.0001	n = 37 2.88; 2.28–3.72	0.0007
PLR	n = 38 41.94; 25.95–80.43	n = 38 60.94; 32.36–102.80	0.4639	n = 37 75.30; 43.53–108.49	0.0096	n = 37 88.80; 48.83–117.08	0.0013
HCT (%)	n = 39 29.40; 25.40–31.55	n = 39 27.30; 23.45–32.40	0.0511	n = 38 37.15; 33.28–39.45	< 0.001	n = 38 37.55; 34.13–40.78	< 0.001
BUN (mg/dL)	n = 35 17.00; 14.50–21.00	n = 32 24.00; 18.00–26.50	< 0.001	n = 33 26.00; 23.00–31.00	< 0.001	n = 34 28.00; 24.00–31.00	< 0.001
Creatinine (mg/dL)	n = 38 1.24; 1.07–1.49	n = 34 1.25; 1.13–1.54	0.1880	n = 37 1.59; 1.38–1.79	< 0.001	n = 36 1.74; 1.46–1.88	< 0.001
ALT (U/L)	n = 38 36.50; 24.25–60.00	n = 34 84.000; 48.00–145.50	0.002	n = 37 51.00; 38.50–68.75	0.2031	n = 36 47.00; 40.00–69.00	0.2579
ALP (U/L)	n = 34 13.00; 8.25–22.50	n = 31 28.00; 19.50–34.00	< 0.001	n = 32 40.00; 29.00–51.00	< 0.001	n = 32 39.50; 27.00–51.00	< 0.001
TP (g/dL)	n = 39 7.60; 7.05–8.95	n = 37 8.30; 7.60–9.70	0.0018	n = 37 7.30; 6.80–7.90	0.0063	n = 36 7.00.; 6.68–7.50	0.0002
ALB (g/dL)	n = 39 2.60; 2.30–2.75	n = 37 2.80; 2.60–3.00	0.0001	n = 37 2.90; 2.70–3.10	< 0.001	n = 36 3.00; 2.88–3.10	< 0.001
GLOB (g/dL)	n = 39 5.00; 4.50–6.30	n = 37 5.60; 4.80–7.10	0.0301	n = 38 4.50; 3.85–5.00	< 0.001	n = 36 4.25; 3.78–4.50	< 0.001
A/G	n = 39 0.51; 0.37–0.59	n = 36 0.50; 0.36–0.60	0.3083	n = 37 0.65; 0.56–0.73	< 0.001	n = 36 0.71; 0.66–0.83	< 0.001
Total bilirubin (mg/dL)	n = 26 0.40; 0.23–0.75	n = 25 0.28; 0.16–0.38	0.0006	n = 25 0.14; 0.12–0.23	0.0003	n = 24 0.12; 0.10–0.18	0.0001

IQR (25 th to 75 th percentile); WBC white blood cell count; NEUT neutrophil concentration; LYMPH lymphocyte concentration; MONO monocyte concentration; PLT platelet concentration; NLR neutrophil-to-lymphocyte ratio; PLR platelet-to-lymphocyte ratio; HCT hematocrit; BUN blood urea nitrogen; ALT alanine aminotransferase; ALP alkaline phosphatase; TP total protein; ALB albumin; GLOB globulin; A/G albumin-to-globulin ratio; n number of data included in the statistical analysis.

^ainitial treatment (week 0) vs Week 1, significant difference, p < 0.05 (bold).

^binitial treatment (week 0) vs Week 7, significant difference, p < 0.05 (bold).

^cinitial treatment (week 0) vs Week 12, significant difference, p < 0.05 (bold).

The dynamics of hematological and biochemical parameters across the active treatment phase (baseline, week 1, week 7, and week 12) were analyzed using the Friedman test for repeated measures. Post hoc comparisons between specific time points (e.g., baseline vs. week 1, baseline vs. week 12) were performed using the Wilcoxon signed-rank test, with p-values adjusted for multiple comparisons using the Bonferroni correction. Paired comparisons between posttreatment (week 12) and long-term follow-up (week 40) data were performed using the Wilcoxon signed-rank test to evaluate the long-term durability of the clinical outcomes. Statistical significance was considered at p < 0.05 for all analyses. All statistical analyses were performed using the Python programming language (version 3.12.12) with the SciPy (version 1.16.3) and pandas (version 2.2.2) libraries.

3. Results

3.1. Study population and clinicopathologic abnormalities at treatment initiation

A total of 117 cats with a presumptive diagnosis of effusive FIP were presented to Prasu Arthorn Animal Hospital between February 2023 and June 2024. Among them, 75 cats were excluded because of loss to follow-up (n = 69), confirmed neoplastic disease (n = 3), and cardiomyopathy (n = 3). Consequently, 42 cats that completed the full treatment protocol were included in the final analysis (Fig. 1). Among the included cats, 21 (50.0%) presented with pleural effusion, and 21 (50.0%) presented with abdominal effusion. No cats exhibited concurrent pleural and abdominal effusion. The cohort comprised 24 intact males (57.1%), 3 castrated males (7.1%), 13 intact females (31.0%), and 2 spayed females (4.8%). Seven breeds were represented, with Domestic Shorthair being the most common (52.4%), followed by Scottish Fold (16.7%), British Shorthair (11.9%), Persian (7.1%), American Shorthair (4.8%), Siamese (4.8%), and Munchkin (2.3%). The median age at diagnosis was 1.0 year (IQR: 0.94–3.00), and the median body weight was 3.45 kg (IQR: 2.50–4.48) (Table 2).

Fig. 1.

Flow chart of inclusion and exclusion criteria and methods used in this study.

Table 2.

Clinical characteristics of the cats in this retrospective study.

	Cats with effusive form FIP (n = 42)
Age at disease onset, year, median [IQR]	1 [0.94–3.00]
Breed, n (%)
Domestic short hair	22 (52.4)
Scottish fold	7 (16.7)
British shorthair	5 (11.9)
Persian	3 (7.1)
American shorthair	2 (4.8)
Siamese	2 (4.8)
Munchkin	1 (2.3)
Sex, n (%)
Male intact	24 (57.1)
Male castrated	3 (7.1)
Female intact	13 (31.0)
Female spayed	2 (4.8)
Female status
Pregnancy	1 (6.7)
Non pregnancy	14 (93.3)
Weight, kg, median [IQR]	3.45 [2.50–4.48]
Sample type, n (%)
Pleural effusion	21 (50.0)
Abdominal effusion	21 (50.0)
Fluid analysis, n (%)
Exudate	20 (57.1)
Modified transudate	15 (42.9)
Positive Rivalta’s test, n (%)	34 (81.0)
Negative bacterial culture, n (%)	30 (76.2)
Positive RT-PCR, n (%)
Pleural effusion	12 (28.6)
Abdominal effusion	16 (38.1)
Dosage of molnupiravir, mg/kg, median [IQR]	14.3 [13.1–17.2]

IQR (25 th to 75 th percentile); RT-PCR, reverse transcriptase polymerase chain reaction.

The initial presenting clinical signs included weight loss, decreased appetite, waxing and waning fever, dyspnea, and abdominal enlargement and distension. Anorexia and depression were the most frequently observed clinical signs at presentation, occurring in 31 (73.8%) and 30 (71.4%) cats, respectively. Additional clinical signs are summarized in Table 3. Rivalta’s test yielded positive results in 34 cats (81.0%). The effusion cytology was available in 35 cats, with 20 (57.1%) and 15 (42.9%) cats being classified with an exudate and modified transudate, respectively. RT-PCR testing for FCoV was performed in effusion samples from 39 cats, of which 28 (71.8%) tested positive. RT-PCR could not be performed in three cats because of insufficient sample volume or financial constraints.

Table 3.

Clinical signs observed at the time of diagnosis in 42 cats with effusive form FIP.

Clinical signs abnormality	Number of cats	%
Anorexia	31/42	73.8
Depress	30/42	71.4
Dyspnea	22/42	52.4
Fever	2/42	4.8
Weight loss	2/42	4.8

Hypoalbuminemia and anemia were the most frequently identified clinicopathological abnormalities, present in 29 (69.0%) and 22 (52.4%) cats, respectively. Additional clinicopathological abnormalities are summarized in Table 4.

Table 4.

Clinicopathological abnormalities present at the time of diagnosis in 42 cats with effusive form FIP.

Clinicopathological abnormality	Number of cats	%
Hypoalbuminemia	29/42	69.0
Anemia	22/42	52.4
Hyperglobulinemia	19/42	45.2
Leukocytosis	16/42	38.1
Monocytosis	15/42	35.7
Neutrophilia	15/42	35.7
Thrombocytopenia	12/42	28.6
Hyperbilirubinemia	10/42	23.8
Hyperproteinemia	10/42	23.8
Lymphocytosis	4/42	9.5
Increase in serum ALT activities	2/42	4.8
Hypoproteinemia	1/42	2.4
Eosinophilia	1/42	2.4
Neutropenia	1/42	2.4
Leukopenia	1/42	2.4

Ten cats received molnupiravir at a dose of 33.3 mg twice daily, whereas 32 cats received a dose of 50 mg twice daily, corresponding to a median administered dosage of 14.3 mg/kg twice daily (IQR: 13.1–17.2). Robust clinical responses were observed. The first follow-up visit (target day 7) occurred at a median of 7 days after treatment initiation (range: 4–14 days). The second follow-up visit (target day 49) occurred at a median of 42 days after the first visit (range: 28–57 days). Meanwhile, the third follow-up visit (target day 84) occurred a median of 35 days after the second visit (range: 21–56 days).

Approximately 85.7% (36/42) of cats demonstrated substantial improvements in cardinal FIP signs by day 7 of treatment, including resolution of depression, anorexia, and dyspnea. Complete clinical resolution and cessation of cavitary effusions were achieved in all cats by day 49. All cats successfully completed the mandatory 84-day (12-week) treatment protocol without any mortalities or dropouts during the active treatment phase (Table 6).

Among cats that presented with pleural effusion, resolution occurred in 18 cats (85.7%) within 7 days of treatment initiation. The remaining three cats (Cat #37, #57, and #47) achieved resolution by day 11, 25, and 29, respectively. Complete resolution was observed in all affected cats by day 49. At day 84, pleural effusion remained resolved in 20 cats (95.2%), whereas one cat experienced relapse. Seventeen cats did not require repeat thoracocentesis during the study period. Meanwhile, four cats required repeat thoracocentesis: two cats (Cat #37 and #57) underwent one thoracocentesis, one cat (Cat #47) required two thoracocentesis procedures during the first week of treatment, and one cat (Cat #19) required one thoracocentesis at week 12 because of relapse of pleural effusion. Complete remission was achieved in 41 cats (97.6%), with one cat (Cat #19) showing relapse of pleural effusion at week 12. Cat #19 developed dyspnea and recurrent pleural effusion on day 84, prompting thoracocentesis and an increase in the dose of molnupiravir from 11.6 mg/kg to 23.3 mg/kg twice daily, along with a subsequent extension of the treatment duration to 168 days. The clinical signs resolved by day 91, and treatment was discontinued on day 168 because of the lack of clinical progression or recurrence of pleural effusion.

Among cats that presented with abdominal distension and effusion, resolution occurred in 16/21 cats (76.2%) within 7 days of treatment initiation. The remaining six cats (Cat #75, #109, #18, #56, #25, and #40) achieved resolution by day 15, 17, 20, 20, 33, and 36, respectively. By day 49 and 84, abdominal effusion completely resolved in all affected cats. No cats required repeat abdominocentesis during the study period. Overall, abdominal effusion resolved within a median of 7 days (IQR: 7–10) (Table 5).

Table 5.

Unpaired comparisons of the change between visits of FIP-associated clinical signs variables.

Variables/comparisons of visits	Molnupiravir
	Deteriorated (n)	Unchanged (n)	Improved (n)	Proportion of improvement
Depress
Day 0 vs day 7	6	0	36	36/42 (85.7%)
Day 0 vs day 49	0	0	42	42/42 (100%)
Day 0 vs day 84	0	0	42	42/42 (100%)
Day 7 vs day 49	0	41	1	1/42 (2.4%)
Day 7 vs day 84	0	41	1	1/42 (2.4%)
Day 49 vs day 84	0	42	0	0/42 (0%)
Anorexia
Day 0 vs day 7	6	0	36	36/42 (85.7%)
Day 0 vs day 49	0	0	42	42/42 (100%)
Day 0 vs day 84	0	0	42	42/42 (100%)
Day 7 vs day 49	0	41	1	1/42 (2.4%)
Day 7 vs day 84	0	41	1	1/42 (2.4%)
Day 49 vs day 84	0	42	0	0/42 (0%)
Dyspnea
Day 0 vs day 7	6	0	36	36/42 (85.7%)
Day 0 vs day 49	0	0	42	42/42 (100%)
Day 0 vs day 84	0	0	42	42/42 (100%)
Day 7 vs day 49	0	41	1	1/42 (2.4%)
Day 7 vs day 84	1	41	0	0/42 (0%)
Day 49 vs day 84	1	41	0	0/42 (0%)
Pleural effusion
Day 0 vs day 7	3	0	18	18/21 (85.7%)
Day 0 vs day 49	0	0	21	21/21 (100%)
Day 0 vs day 84	1	0	20	20/21 (95.2%)
Day 7 vs day 49	0	21	0	0/21 (0%)
Day 7 vs day 84	1	20	0	0/21 (0%)
Day 49 vs day 84	1	20	0	0/21 (0%)
Abdominal distension
Day 0 vs day 7	4	1	16	16/21 (76.2%)
Day 0 vs day 49	0	0	21	21/21 (100%)
Day 0 vs day 84	0	0	21	21/21 (100%)
Day 7 vs day 49	0	21	0	0/21 (0%)
Day 7 vs day 84	0	21	0	0/21 (0%)
Day 49 vs day 84	0	21	0	0/21 (0%)
Abdominal effusion
Day 0 vs day 7	4	1	16	16/21 (76.2%)
Day 0 vs day 49	0	0	21	21/21 (100%)
Day 0 vs day 84	0	0	21	21/21 (100%)
Day 7 vs day 49	0	21	0	0/21 (0%)
Day 7 vs day 84	0	21	0	0/21 (0%)
Day 49 vs day 84	0	21	0	0/21 (0%)

3.2. Dynamics of inflammatory and physiological markers (weeks 0–12)

Longitudinal analysis over the 12-week treatment period revealed statistically significant normalizations in key clinicopathological parameters (Table 6) (Fig. 2, Fig. 3). The systemic inflammation characteristic of effusive FIP was rapidly mitigated. Total leukocyte (white blood cell [WBC]) counts significantly decreased from a baseline median of 16.10 × 10³/µL to 13.60 × 10³/µL by week 1 (p = 0.0148), reaching 10.92 × 10³/µL by week 12 (p < 0.0001), with a median time to normalization of 41.0 days (IQR: 15.0–54.4). Concurrently, the absolute neutrophil counts exhibited a highly significant reduction from baseline to week 1 (p = 0.0019) and week 12 (p < 0.0001). By week 12, the monocyte counts significantly decreased (p ≤ 0.0052), and the lymphocyte counts decreased (p = 0.0336). In addition, the neutrophil-to-lymphocyte ratio (NLR) significantly decreased at week 1, 7, and 12 (p < 0.001). Conversely, the platelet counts significantly increased by week 12 (p = 0.0167), accompanied by a significant increase in the platelet-to-lymphocyte ratio (PLR) at week 7 and 12 (p = 0.0096 and p = 0.0013, respectively). The hematocrit level significantly increased from 29.40% to 37.15% at week 7 and 37.55% at week 12 (both p < 0.001), with a median time to normalization of 49.5 days (IQR: 48.0–57.8).

Fig. 2.

Longitudinal analysis of hematological parameters in cats with FIP. Results are shown as boxplot with median and interquartile for non-normally distributed at initial (week 0) and at week 1, 7, and 12 of treatment. Statistical Significance: Within-group comparisons were performed using the Wilcoxon signed-rank test. Asterisks (*) indicate statistically significant difference compared to baseline (Week 0) (p < 0.05). Panels: (A) White blood cell counts, (B) Neutrophils, (C) Lymphocytes, (D) Monocytes, (E) Platelet, (F) Neutrophil to lymphocyte ratio (NLR), (G) Platelet to lymphocyte ratio (PLR), (H) Hematocrit.

Fig. 3.

Longitudinal analysis of serum biochemistry parameters in cats with FIP. Results are shown as boxplot with median and interquartile for non-normally distributed at initial (week 0) and at week 1, 7, and 12 of treatment, Statistical Significance: Within-group comparisons were performed using the Wilcoxon signed-rank test. Asterisks (*) indicate statistically significant difference compared to baseline (Week 0) (p < 0.05). (I) Blood urea nitrogen, (J) Creatinine, (K) Alanine aminotransferase (ALT), (L) Alkaline phosphatase (ALP), (M) Total protein, (N) Albumin, (O) Globulin, (P) Albumin to globulin ratio (A/G ratio), (Q) Total bilirubin.

Physiological recovery was further evidenced by changes in serum proteins. Serum albumin levels demonstrated a progressive and highly significant increase throughout the treatment course (p < 0.0001), driving a continuous improvement in the A/G ratio from baseline to week 12 (p < 0.0001) (Table 6). The globulin concentrations significantly decreased during treatment at week 7 and 12 (p < 0.001), with a median time to normalization of 50 days (IQR: 39.5–55.5). Accordingly, the A/G ratio significantly increased at week 7 and 12 (p < 0.001), with a median time to normalization of 54.5 days (IQR: 41.8–85.3). The total bilirubin level significantly decreased at all posttreatment time points (p ≤ 0.0006), with hyperbilirubinemia resolving within a median of 7.0 days (IQR: 7.0–48.5).

The serum biochemical parameters also changed significantly over time. The BUN level progressively increased from 17.00 mg/dL at baseline to 24.00, 26.00, and 28.00 mg/dL at week 1, 7, and 12, respectively (all p < 0.001), with corresponding significant increases in serum creatinine at week 7 and 12 (p < 0.001). Despite these increases, the BUN and serum creatinine levels remained within the reference range (16–36 and 0.80–2.40 mg/dL, respectively). The ALT significantly increased at week 1 (p = 0.002), whereas the ALP significantly increased at all posttreatment time points (p < 0.001). The serum protein parameters markedly improved. The total protein level increased at week 1 (p = 0.0018) and subsequently decreased at week 7 and 12 (p ≤ 0.0063), with hyperproteinemia resolving at a median of 49 days (IQR: 41.5–52.5).

3.3. Hepatic safety profile during active therapy

During evaluation, a transient alteration in hepatic enzyme activity was observed during the initial phase of treatment. A statistically significant elevation in ALT was recorded at week 1 (median 84.0 U/L) compared with baseline (median 36.75 U/L) (p = 0.0002). Importantly, this elevation was subclinical and self-limiting. By week 7, the ALT levels had decreased (median 50.0 U/L) and were no longer significantly different from baseline values (p = 0.2031). This normalization was maintained through week 12 (p = 0.2579), confirming that early hepatocellular stress did not progress to sustained hepatic injury.

3.4. Renal safety profile during active therapy

During evaluation of the renal profile, a statistically significant elevation in BUN and serum creatinine levels was identified. The BUN level was elevated at week 1 (median 24.00 mg/dL), week 7 (median 26.00 mg/dL), and week 12 (median 28.00 mg/dL) compared with baseline (median 17.00 mg/dL). Meanwhile, the serum creatinine level was elevated at week 7 (median 1.59 mg/dL) and week 12 (median 1.74 mg/dL) compared with baseline (median 1.24 mg/dL). This elevation in BUN and serum creatinine levels remained within the reference range, suggesting that molnupiravir was not associated with clinically relevant nephrotoxicity.

3.5. Long-term physiological stability and durability of remission (week 12 vs. week 40)

Paired Wilcoxon signed-rank tests were performed on a subset of cats (n = 10) with comprehensive follow-up data at 28 weeks posttreatment cessation (week 40) to evaluate the long-term safety and durability of the clinical outcome posttreatment. The median posttreatment follow-up duration was 201.5 days (IQR: 188–279). All cats (10/10, 100%) that had achieved remission remained relapse-free throughout the follow-up period, and no recurrence of clinical signs was observed between week 12 and week 40 after treatment discontinuation.

The analysis demonstrated a remarkable state of physiological stability. No statistically significant differences in hematological parameters, including WBC (p = 0.3750), neutrophil (p = 0.6250), lymphocyte (p = 0.7695), and platelet counts (p = 0.4922), were observed between week 12 and week 40 (Table 7). Paired analysis showed a significant increase in serum creatinine levels (p = 0.0137), although the values remained within the reference range (0.80–2.40 mg/dL) (Fig. 4). These findings collectively validate a sustained clinical remission and the absence of cumulative or delayed toxicities associated with the 12-week molnupiravir regimen.

Table 7.

Hematological and serum biochemistry in FIP cats at week 12 and 40 of treatment. Results are shown as median with interquartile ranges for non-normally distributed.

Parameter	FIP cats (n = 10)
	Week 12	Week 40	p
WBC (x 103/μL)	10.92; 8.38–15.31	9.64; 6.79–12.07	0.3750
NEUT (x 103/μL)	7.63; 5.42–9.85	5.96; 4.71–9.00	0.6250
LYMPH (x 103/μL)	2.65; 1.86–3.21	2.45; 1.64–2.72	0.7695
MONO (x 103/μL)	0.41; 0.20–0.65	0.21; 0.13–0.40	0.6250
PLT (x 103 cells/mm3)	219.00; 154.00–264.80	210.00; 180.30–243.80	0.4922
NLR	2.88; 2.28–3.72	3.36; 2.49–3.03	0.6250
PLR	88.80; 48.83–117.08	109.30; 88.90–131.53	0.9219
HCT (%)	37.55; 34.13–40.78	38.10; 35.28–41.56	0.0137
BUN (mg/dL)	28.00; 24.00–31.00	25.50; 22.25–27.50	0.5039
Creatinine (mg/dL)	1.74; 1.46–1.88	1.95; 1.73–2.20	0.0137
ALT (U/L)	47.00; 40.00–69.00	46.50; 40.50–54.00	0.3633
ALP (U/L)	39.50; 27.00–51.00	34.00; 27.75–43.00	0.5078
TP (g/dL)	7.00.; 6.68–7.50	7.20; 7.00–7.48	0.4609
ALB (g/dL)	3.00; 2.88–3.10	3.05; 2.85–3.25	0.5391
GLOB (g/dL)	4.25; 3.78–4.50	4.30; 4.05–4.58	0.6484
A/G	0.71; 0.66–0.83	0.69; 0.67–0.76	1.0000
Total bilirubin (mg/dL)	0.12; 0.10–0.18	0.30; 0.13–0.38	0.2500

IQR (25 th to 75 th percentile); WBC white blood cell count; NEUT neutrophil concentration; LYMPH lymphocyte concentration; MONO monocyte concentration; PLT platelet concentration; NLR neutrophil-to-lymphocyte ratio; PLR platelet-to-lymphocyte ratio; HCT hematocrit; BUN blood urea nitrogen; ALT alanine aminotransferase; ALP alkaline phosphatase; TP total protein; ALB albumin; GLOB globulin; A/G albumin-to-globulin ratio; n number of data included in the statistical analysis.

Week 12 vs Week 40, significant difference, p < 0.05 (bold).

Fig. 4.

Long-term analysis of hematological and serum biochemistry in FIP cats (n = 10) at week 12 and 40 of treatment.

Between time-point comparison of hematocrit levels between Week 12 and Week 40 in cats (n = 10) using the paired Wilcoxon signed-rank tests. Between time-point comparison of serum creatinine between Week 12 and Week 40 in cats (n = 10) using the paired Wilcoxon signed-rank tests.

4. Discussion

The introduction of nucleoside analog antiviral drugs has significantly changed the clinical management of FIP. Current international guidelines generally recommend GS-441,524, remdesivir, and molnupiravir as antiviral therapies, though molnupiarvir is typically reserved as rescue treatment for cats that relapse after initial antiviral therapy (Tasker et al., 2023, 2026; Thayer et al., 2022). The present study expands upon these favorable clinical outcomes, offering additional evidence that supports the potential role of molnupiravir as a first-line therapeutic option in cases of naturally occurring effusive FIP. Although the acute efficacy of molnupiravir has been documented, there are limited data regarding the long-term durability of clinical remission and safety profile posttreatment. This retrospective study contributes to the current literature by providing an extended 40-week follow-up on the hematological, biochemical, and clinical stability of cats treated with molnupiravir as first-line treatment for naturally occurring effusive FIP. The findings showed that molnupiravir was associated with a high remission rate, rapid resolution of FIP-associated clinical signs and effusion and sustained clinical and clinicopathological stability following treatment discontinuation. Importantly, long-term follow-up revealed no evidence of disease relapse and no clinically meaningful deterioration in hematological or biochemical parameters after discontinuing treatment.

In the present cohort, a complete remission rate of 97.6% was achieved, exceeding previously reported remission rates for molnupiravir (75%–89%) (Černá et al., 2026; Clark et al., 2025; Reagan et al., 2024; Roy et al., 2022; Sase, 2023). This favorable outcome may be attributed to the consistent implementation of molnupiravir as first-line treatment, strict adherence to a standardized minimum treatment duration of 84 days, and individualized dose adjustments guided by clinical response. Furthermore, the availability of structured long-term follow-up enabled the confirmation of sustained remission after treatment discontinuation. The remission rate observed in the present study appears comparatively high when compared with other nucleoside analog antiviral drugs used for treating FIP, including GS-441,524 and remdesivir, which have reported remission rates of 69% and 86%, respectively (Pedersen et al., 2019; Renner et al., 2025). Collectively, these findings further support the use of molnupiravir as a clinically effective and well-tolerated first-line treatment option for cats with effusive FIP, particularly in settings with limited access to alternative antiviral agents.

In the present study, the median dose of molnupiravir was 14.3 mg/kg twice daily for a minimum treatment duration of 84 days. This dosing regimen is consistent with that reported in previous studies (10–15 mg/kg twice daily) (Černá et al., 2026; Clark et al., 2025; Reagan et al., 2024; Sase, 2023), suggesting that the observed favorable outcomes were achieved within established therapeutic ranges.

Previous studies have reported improved FIP-related clinical signs following molnupiravir treatment, with rapid clinical response observed within 2–42 days after initiation (Clark et al., 2025; Roy et al., 2022; Sase, 2023). In the present study, most cats demonstrated marked improvement within the first week of treatment, with complete resolution of clinical signs by day 49. Pleural and abdominal effusions also resolved rapidly, with a median time to resolution of 7 days. Moreover, all cats achieved resolution of effusion by day 49. One cat experienced relapse of pleural effusion at day 84, which resolved within 7 days following treatment adjustment. These findings suggest that molnupiravir may be effective as first-line and rescue treatment, consistent with previous reports (Černá et al., 2026; Clark et al., 2025; Reagan et al., 2024; Roy et al., 2022; Sase, 2023; Yoshida et al., 2025).

During molnupiravir treatment, hematocrit levels normalized within a median of 49.5 days. The leukocyte counts also returned to normal within 41.0 days. The hematocrit significantly increased over time, accompanied by progressive improvement in leukocyte parameters. Furthermore, the NLR and PLR decreased during therapy, likely reflecting the attenuation of systemic inflammation.

Hyperproteinemia, hyperglobulinemia, and A/G ratio normalized within a median of 49, 50, and 54.5 days, respectively. In a previous study using parenteral remdesivir with or without transition to oral GS-441,524, hyperproteinemia, hyperglobulinemia, and A/G ratio normalized within 21, 35, and 49 days, respectively (Coggins et al., 2023). The comparatively longer time to normalization observed in the present study may reflect differences in antiviral regimen, administration route, or disease severity. Overall, the resolution of these protein abnormalities suggested the attenuation of immune-mediated inflammation and sustained reduction of systemic inflammatory activity.

In this study, BUN and serum creatinine levels significantly increased during treatment. During long-term follow-up, serum creatinine levels remained significantly increased. However, this change was not considered clinically significant as it was not associated with clinical signs of renal dysfunction, progressive deterioration, or consistent ultrasonographic abnormalities. Importantly, no cases of acute kidney injury have been reported in cats treated with molnupiravir (Černá et al., 2026; Reagan et al., 2024; Romanelli et al., 2024; Roy et al., 2022; Sase, 2023) or other nucleoside analog antiviral drugs (Coggins et al., 2023; Pedersen et al., 2019; Renner et al., 2025; Zuzzi-Krebitz et al., 2024). In human studies, molnupiravir is not primarily eliminated via the renal pathway and has generally been well tolerated in patients with severe renal impairment (Duncan et al., 2024; Maas et al., 2024), further supporting the low likelihood of direct nephrotoxicity. Moreover, several factors may influence serum creatinine levels, including age-related physiological changes, improved muscle mass following recovery from chronic illness, hydration status, or preexisting renal susceptibility (Greene et al., 2014; Sparkes et al., 2016). Further studies are needed to evaluate clinicopathological parameters, including urinalysis, and outcomes in cats with FIP treated with molnupiravir, particularly those with concurrent or preexisting chronic kidney disease.

A critical observation in this cohort was the transient, yet statistically significant, elevation of ALT levels during the first week of treatment. Transparent reporting and interpretation of this hepatocellular perturbation are vital for clinical practice. Indeed, these findings are consistent with previous reports describing hepatic elevations associated with molnupiravir therapy (Černá et al., 2026; Clark et al., 2025; Reagan et al., 2024; Roy et al., 2022; Sase, 2023). This elevation was hypothesized to be multifactorial. It may reflect a mild, self-limiting drug-induced liver injury associated with the hepatic metabolism of the ribonucleoside prodrug. Alternatively, it may be secondary to the acute inflammatory response associated with viral clearance and the subsequent remodeling of pyogranulomatous lesions within the liver (Duncan et al., 2024; Maas et al., 2024). Clinically, this ALT elevation was asymptomatic and naturally resolved by week 7 without requiring dose adjustment or treatment interruption. This indicates that although hepatic monitoring is advisable during the early phase of treatment, mild transient ALT spikes do not inherently necessitate molnupiravir discontinuation.

A primary concern with the prolonged use of experimental antivirals is the potential for cumulative toxicity, particularly delayed nephrotoxicity or bone marrow suppression. The extended follow-up data in this study specifically addresses this concern. The comparative analysis between posttreatment and long-term follow-up data demonstrated stable serum creatinine levels and sustained hematocrit and leukocyte profiles. The absence of delayed adverse effects robustly supports the long-term safety profile of the 12-week molnupiravir protocol.

This study has several limitations inherent to its retrospective design. First, the data relied on clinical veterinary records, resulting in variations in exact sampling times and some missing data points in the extended follow-up phase. Second, the lack of pharmacokinetic and pharmacodynamic monitoring precludes the correlation of specific plasma concentrations of molnupiravir and its active metabolite (EID-1931) and clinical outcomes or transient elevations in serum ALT activity. Third, comprehensive renal evaluation, including urinalysis and symmetric dimethylarginine (SDMA) measurement, was not consistently available due to the retrospective study, as these assessments were frequently omitted because serum creatinine concentration in all cats remained within reference interval. Consequently, the potential for subtle or subclinical renal dysfunction could not be fully evaluated. Further prospective studies incorporating, comprehensive renal assessments are warranted. Fourth, quantitative monitoring of feline coronavirus (FCoV) viral loads is not routinely performed in clinical practice following clinical resolution. Consequently, the absence of serial post-treatment quantitative RT-PCR testing (e.g., monitoring FCoV RNA loads in the blood or feces posttreatment) limits our ability to definitively confirm complete viral eradication (virological cure) versus sustained latent viral suppression. Future prospective studies incorporating longitudinal molecular diagnostics and pharmacokinetic profiling are needed to fully elucidate the mechanism of long-term viral clearance.

5. Conclusion

This 40-week retrospective analysis demonstrated that molnupiravir is a highly effective and well-tolerated first-line treatment for naturally occurring effusive FIP. A 12-week treatment protocol not only yields rapid resolution of clinical signs and inflammatory markers but also establishes a durable clinical remission. The transient elevation in hepatic enzymes observed during early treatment is self-limiting and does not impede clinical recovery. Furthermore, the absence of delayed renal or hematological toxicities up to 28 weeks posttreatment confirms the long-term safety of this therapeutic regimen. These findings provide substantial evidence supporting the integration of molnupiravir into standard clinical management for effusive FIP. However, further studies are needed to establish virological cure.

CRediT authorship contribution statement

Thiti Surakitkoson: Writing – original draft, Project administration, Methodology, Data curation, Conceptualization. Phuttipan Channgam: Writing – review & editing, Supervision, Formal analysis. Walasinee Sakcamduang: Writing – review & editing, Supervision, Formal analysis. Jeerawat Soonthornsit: Writing – review & editing, Supervision, Formal analysis, Conceptualization. Rungrote Osathanon: Writing – review & editing, Supervision, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.