Introduction
Feline infectious peritonitis is a fatal and progressive illness caused by feline coronavirus (FCoV), affecting domestic and wild felids globally.3 Feline coronavirus manifests in 2 forms: the low-virulence feline enteric coronavirus (FECV) and the high-virulence FIP virus (FIPV).1 Feline infectious peritonitis can be exhibited in 2 forms: the “wet” form, characterized by fluid accumulation in body cavities, and the “dry” form, which involves granulomatous lesions in various organs.2 Despite being extensively studied, FIP remains without a definitive diagnostic test, an approved efficacious treatment, or a dependable vaccine. It is widely believed that FIPV arises from the accumulation of mutations in FECV, which are favored by high frequencies of FCoV replication and transmission, particularly in multicat environments.3,4 This enigmatic pathogenesis of FIP creates substantial diagnostic difficulties in distinguishing FIPV infections from common mild FECV ones.
Studies5,6 investigating the epidemiology of FIP in cats have identified risk factors for the development of FIP such as age, breed, sex, seasons, coinfection, and multicat environments. All these identified risk factors play a crucial role in guiding diagnostic strategies, therapy, and disease control strategies.
Early and accurate diagnosis is crucial for improving the quality of life for those infected with FIPV. However, definitively diagnosing FIP can be extremely challenging, especially antemortem, due to the limitations of available diagnostic tests and the overlapping clinical signs with other feline diseases. The choice of the samples may vary depending on the clinical access, the preferences of the veterinarian, and the clinical presentation of the cat.7
In cases where FIP is suspected, a combination of tests and appropriate samples may be necessary to obtain an accurate diagnosis. Polymerase chain reaction testing for FCoV RNA has become one of the most reliable and rapid diagnostic indicators for FIP in suspected cases.8,9 However, it has been argued that the detection of FCoV genomic RNA using PCRs may not always indicate a definite diagnosis of FIP, as FCoV viremia has been observed in clinically healthy cats.10 This argument is grounded in the understanding that FIPV replicates mainly within monocytes/macrophages, unlike the less virulent FECV counterpart. The diagnostic usefulness of PCR was evaluated in different types of samples11; however, the reliability of this test for FIP diagnosis depends largely on the choice of test specimens.
Among the key questions asked about FIP by clinicians, the 2 most important ones concern the risk factors and optimal choice of tissue or fluid samples for viral detection. While most studies addressing these 2 essential questions have been conducted with small sample sizes,10,12–14 our work comprehensively analyzed the viral presence of FCoV in 14,035 submissions from across the US. The statistical analysis of this extensive data set confirmed some previous findings and also shed novel light on FIP risk factors. The results also suggested an optimal choice of samples for diagnostic testing.
Methods
Clinical sample collection
Convenience samples (n = 14,035) submitted to the Molecular Diagnostic Laboratory at the Auburn University College of Veterinary Medicine from 2016 to 2023, originating from 47 US states, were utilized in this study. These samples had been submitted for molecular diagnosis due to clinical signs and tests suggestive of FIP. Information such as age, breed, and types of submitted feline samples was recorded.
Extraction of nucleic acids
Total nucleic acid extraction from the submitted samples was performed with glass fiber matrix binding and elution with a commercial kit (High-Pure PCR Template Preparation Kit; Roche Diagnostic) following the manufacturer’s instructions and described previously.15 For each specimen, 400 μL of fluid or biopsy tissue in saline was mixed with an equal volume of binding buffer and eluted in a final volume of 100 μL.
Reverse transcriptase quantitative PCR
The FCoV MN gene PCR utilized in this study followed the original approach reported by Simons et al16 with minor modifications. The reverse transcriptase quantitative PCR (RT-qPCR) was designed to quantify the replicating FCoV and amplify a 281-bp FCoV genomic region that spans the junction of M and N genes, as described.10
The assay was performed with 25-ng standardized cDNA input as a 1-step RT-qPCR modeled on the proprietary Auburn University Molecular Diagnostics PCR thermal design (US patent 7,252,937). The sensitivity of this assay was validated by serial dilution of cDNA standard templates. The limit of detection was a single mRNA copy per reaction as evident in the Poisson distribution of positive and negative amplification reactions at the limiting dilution. Validation of the specificity was performed by sequence determination of positive amplifications in this study.
Fluorescence resonance energy transfer RT-qPCR was performed on a Roche light cycler 480 II system (Roche Molecular Biochemicals) containing 2.0-U Platinum Taq DNA polymerase (Invitrogen) and 0.0213-U ThermoScript reverse transcriptase (Invitrogen). Thermal cycling was preceded by a 10-minute reverse transcription reaction at 55 °C followed by a 4-minute denaturation at 95 °C and 30 fluorescence acquisition cycles of 10 seconds at 95 °C, 8 seconds at 58 °C with fluorescence acquisition, 30 seconds at 67 °C, and 30 seconds at 72°C with the melting curve determined by 1 minute at 95 °C and 2 minutes at 42 °C and increasing to 74 °C with continuous fluorescence reading. The reference FIPV as a quantitative standard used in this study was FIPV strain 79-1146 (American Type Culture Collection).
Analysis of multiple types of submitted samples from individual cats
Among 14,035 submissions included in this study, multiple types of samples were submitted from 389 individual cats. These samples encompassed a variety of sources, with whole blood (n = 330), peritoneal fluid (286), lymph node (63), feces (50), kidney (19), spleen (14), pleural fluid (8), liver (8), colon (7), CSF (4), aqueous humor (3), lung (3), omentum (2), intestine (1), bone marrow (1), and testicle (1) being among them. This study specifically compared the FCoV positivity among multiple submissions when they originated from the same cats.
Statistical analysis
All data were analyzed with STATISTICA 7.1 software (Statsoft). Summary statistics describing the overall FCoV detection rates associated with different risk factors (sex, age, and types of samples) were performed. The data were presented as mean and ± SD or CI. χ2 tests were employed for preliminary univariate analyses to ascertain the significance of the relationships between sex, age groups, neutered status, various types of samples, breeds, and the presence of FCoV. The univariate logistic regression model used age, gender, breed, and kinds of submitted samples as independent and categorical variables (age, gender, breed, and types of samples) to assess the risk factor and existence of FCoV. Odds ratios with 95% CI were calculated to quantify the strength of the associations between the risk factors and FCoV detection. Out of the 74 distinct breeds, we specifically focused on 24 breeds that had a sample size of 30 or greater to calculate the odds ratio. A P value < .05 was considered statistically significant.
Results
Demographic information of the cats and the submitted samples
The average age of the cats from which the samples were submitted in this study was 3.51 years, ranging from 1 month to 17 years old (SD, 3.88 years; Supplementary Table S1).
In total, the submitted samples represented 77 different feline breeds, including domestic shorthair (n = 7,891), followed by domestic longhair (729), domestic mediumhair (529), Siamese (348), Maine Coon (291), Ragdoll (275), Persian (189), Bengal (160), Siberian (155), Sphynx (147), British Shorthair (143), Scottish Fold (113), and unknown mixed breeds (172). These samples, as well as other samples with < 100 submissions, are listed in Supplementary Table S2.
The main types of submitted samples included peritoneal fluid (n = 7,720), whole blood (4,496), lymph node (360), pleural fluid (197), urine (145), kidney (124), intestine (98), spleen (92), liver (83), cerebrospinal fluid (CSF) (73), aqueous humor (40), lung (22), and bone marrow (12; Table 1). Other samples with < 10 submissions included the brain, eye, omentum, colon, testicle, and skin.
Positivity of feline coronavirus detection in different types of submitted samples.
| Sample | Negative | Positive | Total | Positivity | Viral copies (log10*) |
|---|---|---|---|---|---|
| Peritoneal | 3,289 | 4,431 | 7,720 | 0.57 | 2.97 ± 1.34 |
| Blood | 4,096 | 400 | 4,496 | 0.09 | 1.63 ± 0.88 |
| Lymph node | 198 | 162 | 360 | 0.45 | 2.80 ± 1.37 |
| Pleural fluid | 119 | 78 | 197 | 0.40 | 2.70 ± 1.12 |
| Urine | 69 | 76 | 145 | 0.52 | 3.19 ± 1.33 |
| Feces | 97 | 43 | 140 | 0.31 | 2.78 ±1.36 |
| Kidney | 76 | 48 | 124 | 0.39 | 2.95 ± 1.64 |
| Intestine | 56 | 42 | 98 | 0.43 | 2.46 ± 1.49 |
| Spleen | 77 | 15 | 92 | 0.16 | 2.74 ± 1.27 |
| Liver | 69 | 14 | 83 | 0.17 | 2.80 ± 1.37 |
| CSF | 66 | 7 | 73 | 0.10 | 2.83 ± 0.63 |
| Aqueous humid | 33 | 7 | 40 | 0.16 | 2.27 ± 0.99 |
| Lung | 19 | 3 | 22 | 0.14 | 2.20 ± 3.00 |
| Bone marrow | 12 | 0 | 12 | 0.00 | 0 |
*The viral copy number in the feline coronavirus–positive samples.
Higher detection rate of FCoV in young cats than in old ones
Fluorescence resonance energy transfer PCR detected replicating FCoV in 39.1% of submitted samples (5,491 of 14,035) in this study. Overall, significantly higher detection rates of FCoV were observed in younger cats compared to older ones, with detection rates of FCoV declining as cats aged (Figure 1; Supplementary Table S1 and Supplementary Table S3). Cats aged 2 to 10 years exhibited a significantly lower FCoV detection rate (1,762 of 5,167 [34.1%]) than cats aged 0 to 1 year (3,250 of 6,979 [46.6%]; P < .001) and a rate significantly higher than the cats above 10 years old (268 of 1,238 [21.6%] P < .001). Cats aged 0 to 1 year have a 2-fold higher possibility of being FCoV positive than cats ≥ 2 years old.
Detection rates of feline coronavirus (FCoV) in cats across various age groups. A—The detection rates of FCoV declined as cats aged. Logistic regression analysis was employed to analyze the FCoV detection rates among cats of different age groups. It was defined that 1 year means ages 0 to 1 year, 2 years mean 1.1 to 2 years old, and so forth. The P values from logistic regression analysis can be found in Supplementary Table S3. B—Cats aged 2 to 10 years exhibited a significantly lower FCoV detection rate (1,762 of 5,167 samples [34.1%]) than cats aged 0 to 1 year (3,250 of 6,979 samples [46.6%]) and a rate significantly higher than the cats above 10 years old (268 of 1,238 samples [21.6%]; P < .001; χ2 test). Error bar, mean ± 95% CI.
Citation: Journal of the American Veterinary Medical Association 2024; 10.2460/javma.24.03.0208
Higher FCoV detection rates in male than female cats
The detection rate of FCoV in male cats was 42.4% (3,536 of 8,324), statistically significantly higher than the 34.3% in female cats (1,799 of 5,242; P < .001; Figure 2). The FCoV detection rate was statistically significantly higher in male cats than in female ones. However, no statistically significant association was observed between castrated and intact male cats (2,645 of 6,361 [41.6%] vs 138 of 328 [42.0%]) and between spayed female and intact cats (1,308 of 3,887 [33.7%] vs 48 of 129 [37.2%]). While male cats showed an overall higher detection rate of FCoV than female cats across different ages in this study, the difference was significant specifically for cats under 4 years of age (Figure 3).
Comparison of the detection rates of FCoV in male and female cats. The detection rate of FCoV in male cats was 42.4% (3,536 of 8,324 cats), significantly higher than the 34.3% in female cats (1,799 of 5,242 cats; A). However, no significant difference was observed between intact male and castrated cats (138 of 328 vs 2,645 of 6,361 cats) and intact female cats and spayed cats (48 of 129 vs 1,308 of 3,887 cats; C). Error bar, mean ± 95% CI.
Citation: Journal of the American Veterinary Medical Association 2024; 10.2460/javma.24.03.0208
Detection rates of FCoV in male and female cats across various age groups. While the male cats showed an overall higher detection rate of FCoV than female cats across different ages in this study, the difference was significant specifically for cats under 4 years of age. Error bar, mean ± 95% CI.
Citation: Journal of the American Veterinary Medical Association 2024; 10.2460/javma.24.03.0208
Lower detection rates of FCoV in mixed-breed cats compared to the purebred cats
Among the 77 feline breeds included in this study, 25 breeds with more than 30 submissions were analyzed by means of logistic regression analysis. The statistical analysis demonstrated that British Shorthair cats (purebred) demonstrated a significantly higher detection rate of FCoV (positivity rate, 64.3%; OR, 2.81; 95% CI, 1.99 to 3.96; P < .001) than other cats. Domestic shorthair cats (mixed breed) had a significantly lower FCoV detection rate (positivity rate, 37.7%; OR, 0.81; 95% CI, 0.75 to 0.88; P < .001) than other cats (Figure 4; Supplementary Table S2 and Supplementary Table S4).
Differences in FCoV detection rates among different cat breeds. Logistic regression analysis was conducted to compare the detection rates of FCoV across 25 feline breeds with more than 30 submissions in this study. Particularly, a significant lower FCoV detection rate was found in domestic shorthairs (OR, 0.81). In a comparison, a significantly higher detection rate of FCoV was found in British Shorthairs (OR, 2.81), Birmans (OR, 2.13), Siberians (OR, 2.10), Persians (OR, 1.53), and Ragdolls (OR, 1.29). The p values and OR from logistic regression analysis can be found in Supplementary Table S4. Error bar, mean ± 95% CI.
Citation: Journal of the American Veterinary Medical Association 2024; 10.2460/javma.24.03.0208
Significantly higher FCoV in peritoneal fluids and tissues than in whole blood
We employed logistic regression analysis to analyze the FCoV detection rates across 14 distinct sample types, each with over 10 submissions (Figure 5; Table 1; Supplementary Table S5). The highest detection rates were observed in peritoneal fluid samples (4,431 of 7,720 [57.4%]) and urine samples (76 of 145 [52.4%]), significantly higher than in samples of whole blood (400 of 4,496 [8.9%]), CSF (7 of 73 [9.6%]), lung (3 of 22 [13.6%]), spleen (15 of 92 [16.3%]), liver (14 of 83 [16.9%]), aqueous humor (7 of 40 [17.5%]), feces (43 of 140 [30.7%]), kidney (48 of 124 [38.7%]), pleural fluid (78 of 197 [39.6%]), lymph node (162 of 360 [45.0%]) and bone marrow (0 of 12 [0%]). Additionally, the detection rate in whole blood (positivity, 8.9%; OR, 0.08; 95% CI, 0.07 to 0.09; P < .001) was significantly lower than in most tissue samples, while kidney and lymph nodes exhibited higher detection rates compared to other tissue samples.
Comparison of FCoV positivity and viral burdens in different types of samples. A—Logistic regression analysis was utilized to compare the detection rates of FCoV across 14 types of submitted samples with more than 30 submissions in this study. The significantly higher detection rates were observed in peritoneal fluid (OR, 7.51), urine (OR, 1.72), and lymph node (OR, 1.28). In comparison, a significantly lower detection rate was observed in blood (OR, 0.09), CSF (OR, 0.16), lung (OR, 0.24), spleen (OR, 0.30), liver (OR, 0.31), aqueous humor (OR, 0.33), and feces (OR, 0.69). The P values and OR from logistic regression analysis can be found in Supplementary Table S5. B—Error bar, mean ± 95% CI.
Citation: Journal of the American Veterinary Medical Association 2024; 10.2460/javma.24.03.0208
The comparison of the viral copies among the FCoV-positive samples showed that the viral burden in whole blood (101.63) was significantly lower than in urine (103.19), peritoneal fluid (102.97), kidney (102.95), CSF (102.83), feces (102.78), pleural fluid (102.70), lymph node (102.54), intestine (102.46), and bone marrow (0; Table 1). In addition, the viral copy numbers in urine (103.19) and peritoneal fluid (102.97) were significantly higher than in lymph node (102.54; Figure 5).
Analysis of FCoV in multiple sample submissions from the same cats
Among 389 cats with multiple sample submissions, the FCoV positivity (77 of 331 [23%]; P < .01) was significantly lower than those of any other types of samples (body fluids, 93%; aqueous humor, 2 of 2; tissues, 131 of 155 [85%]; feces, 34 of 50 [68%]). In addition, the FCoV positivity was the highest among all types of submitted samples, and tissue had a significant higher FCoV positivity than in feces (P < .01). Among the multiple samples, both whole blood and peritoneal fluids were submitted from 234 cats. The blood samples positive for FCoV had an average copy number of 102.93 (SD, 102.91) per sample, significantly lower than the 105.39 (SD, 106.31) in the peritoneal fluids (P = .02).
Further analysis of these 234 cats demonstrated a negative correlation between FCoV detection rates in feces and other organs and tissues. Interestingly, out of 47 cats that were positive in blood and peritoneal fluids, all 3 submitted fecal submissions were found to be FCoV negative. Furthermore, out of 7 cats that were negative in both blood and peritoneal fluids, all 3 submitted fecal samples were found to be FCoV positive. Among the total 50 of fecal samples in multiple submissions, 34 were found to be FCoV positive. For these 34 cats that had FCoV-positive feces, 23.4% of other submitted samples were found to be positive for FCoV, including 3 of 31 in the whole blood, 7 of 11 in peritoneal fluid, 1 of 3 in the lymph node, 0 of 1 in the kidney, and 0 of 1 in the lymph node. On the other hand, for the 16 cats that had negative fecal tests for FCoV, 69.0% of other submitted samples were FCoV positive (6 of 15 in blood, 9 of 9 in peritoneal fluid, 1 of 1 in CSF, and 4 of 4 in lymph node).
Discussion
The data from this nationwide study, comprising 14,035 clinical sample submissions for FIP diagnosis, reaffirmed the findings of previous studies and shed novel insights into associated risk factors and optimal choice of sample selection for diagnosis.
In our investigation, we found that cats aged 0 to 1 year exhibited a greater likelihood of testing positive for FCoV compared to cats aged ≥ 2 years, aligning with previous studies.17 This suggests that young cats may contact FCoV before their immune systems reach full maturity, facilitating efficient virus replication and favoring mutations from FECV to FIPV.3,12,13,18 Young cats may also experience greater stress due to factors such as relocation, vaccination, neutering, and separation from parent cats.6,14 These stressors could render young cats more susceptible to FIPV compared to their adult counterparts. Stress has been implicated in the increased risk of FCoV shedding and subsequent FIP development.1,17 Stress triggers the release of glucocorticoids, which likely suppress cell-mediated immunity and facilitate increased FCoV replication.1,19
Interestingly, our study also detected a significantly higher positivity of FCoV in male cats compared to females, mirroring trends similarly observed in COVID-19 cases in male and female individuals.20 Research into FCoV and gender predisposition suggests that males may be at a higher risk of developing more severe manifestations of FIP.12,21–24 However, other reports have stated that males and females have similar risks of developing FIP.25 Sex-based differences may be related to sex hormones, particularly androgens, which could negatively impact the immune system, potentially increasing the risk of virus replication and mutation.26 This gender predisposition aligns with findings from other infections affecting cats such as FIV27 and FeLV,28 indicating a potential behavioral, hormonal, or physiological basis for the differences in susceptibility and severity between male and female cats. Results of this study suggested that male cats may be at a higher risk of developing FIP than female ones, likely due to the differences in sex hormone and the derived immune responses.
Although we reported gender bias for FCoV detection in the present study, we observed no statistically significant difference in FCoV detection rates between intact cats and those that had been castrated/spayed. Gender, specifically intact males, has been identified as a risk factor for FIP in previous studies.18,24,29 Contrary to expectation, certain earlier studies failed to observe any form of gender bias for FIP.14,30 Discrepancies may arise from various factors, including differences in sample sizes and different populations.
In this study, an increased FCoV detection rate has been observed in certain purebred varieties, particularly the British Shorthair, which demonstrated a significantly higher detection rate of FCoV than other cats. Pesteanu-Somogyi et al18 reported the increased risk of developing FIP in certain breeds, notably the Birman, Ragdoll, Bengal, Rex, Abyssinian, and Himalayan breeds. Reduced genetic diversity in purebred cats may result in decreased disease resistance and environmental adaptability compared to mixed-breed cats, potentially explaining the high prevalence of FCoV infection in purebred cats, including certain breeds.12,13,25,26
Our findings indicated a markedly lower detection rate and copy number of FCoV in whole blood compared to most tissue samples, which supports the previous findings.31 Pedersen et al reported that even in cats with highly fulminant experimentally induced FIP, viremia is either absent or falls below the reliable detection limits of highly sensitive RT-qPCR throughout all stages of the infection.31 Other studies32 reported on inconsistent FCoV detection in the blood of kittens inoculated with different doses of 2 independent FECV field strains, UCD and RM. In a virus persistence study, cats infected with FCoV type I were all found to be positive for FCoV for at least one of the examined tissues with or without blood viremia.33 Therefore, efforts for virus detection should focus on tissues and effusions presumably containing FIPV-infected macrophages.
An unexpected and interesting finding in this study was the high detection rate and viral burdens of FCoV in urine and kidney samples. Generally, urine is reported to be an unlikely source of infection.3 Feline infectious peritonitis virus is strongly cell and tissue bound, with shedding in urine typically occurring only in specific scenarios, such as when lesions disrupt the renal collecting ducts or intestinal wall, leading to the potential shedding of the virus in urine.3 Urine is more likely diagnosed for abnormalities (proteinuria) in support of a diagnosis if other clinical signs and test results are consistent with FIP.3 Interestingly, a handful of SARS-CoV-2 studies34,35 have also reported viral shedding in urine and explored its potential correlation with disease severity. The findings of the present study provide compelling evidence to explore the possibility of urine as a convenient and valuable sample for the FIP diagnosis. A correlation between renal involvement and urine positivity needs to be studied. Nevertheless, further studies are warranted to evaluate urine for its diagnostic value in FIP.
Among 14,035 submissions included in this study, multiple types of samples were submitted from 389 individual cats. We additionally analyzed these multiple samples submitted from the same cats, and the results further confirmed the findings from the analysis of the nationwide samples. Significantly higher FCoV detection rates and viral loads were found in peritoneal fluids and urine, compared to the blood when submitted at the same time in multiple sample submissions. One key finding from multiple submissions was the negative correlations in the FCoV detection rates in feces and other types of submitted samples. When FCoV was detected in feces, it was less likely to be detected in other organs and tissues, and vice versa. As fecal detection more likely indicates the shedding of FCoV in cats rather than being connected to ongoing FIP infection,4,9 further studies are warranted to identify the genotypes of FCoV in feces and other types of submitted samples, correlating the results of FIP diagnosis by other methods such as immunohistochemistry.
One significant limitation of this study is the lack of confirmed diagnosis of FIP for the cats from which samples were included, due to the nature of convenience sample submission in this study. However, consistent communication with clinicians during reporting of results indicates strong correlations between replicating mRNA PCR and FIP diagnosis. Another limitation of this study is the detection of the whole population of FCoV via subgenomic mRNA detection that amplified all RNA species with maximum sensitivity and specificity. It is well-known that infection by a specific variant can quickly result in the emergence of genetically diverse clades of coronavirus.4,36 Cats in laboratory settings, when inoculated with a mixture of 2 closely related variants originating from the same FIP-infected cat, exhibited illness caused by either one of the variants, but not both simultaneously.4 As a result, the RT-qPCR used in our study might be beneficial and valuable to identify quasispecies of virulent FCoV rather than only targeting classical FIPV. In fact, many studies report the identification of diverse FCoV strains in FIP cats.37,38 Nevertheless, the results of the present study should be further confirmed with immunohistochemistry as the gold standard test, and consideration should be given to the clinical presentation of the cats and other tests.
In this study, statistical analyses were performed on the positivity of FCoV in cats of different ages (1 to 17 years old), different sexes, 23 feline breeds, and 14 different types of submitted samples. Ideally, a hierarchical approach for multivariable comparison should be used to analyze the data, taking into account the interactions of different variables. However, given the multiple groups for each variable in this work, we decided to focus on the analysis of individual variables.
In conclusion, this nationwide study sheds new light on the risk factors associated with FIP and the optimal choice of sample submission for its diagnosis. Our findings highlighted that young cats aged 0 to 1 year exhibit a greater likelihood of testing positive for FCoV, potentially due to stressors and immature immune systems. Additionally, similar to COVID-19 in humans, male cats appear to have a higher positivity of FCoV detection, suggesting a gender predisposition. Purebred cats, especially British Shorthairs, show increased susceptibility to FCoV infection, emphasizing the importance of genetic factors. Detection of FCoV in tissues such as peritoneal fluid, urine, kidney, and lymph node proved valuable in our study, potentially aiding in diagnosis. However, limitations such as the lack of confirmed FIP diagnoses and the need for further validation of detection methods underscored the necessity for continued research. Overall, this study contributes to our understanding of FIP epidemiology and underscores the need for improved diagnostic strategies and management approaches.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org.
Acknowledgments
The authors thank Dr. Laura Huber for her valuable advice on the statistical analysis in this work.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.
Funding
The authors have nothing to disclose.
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