JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM 

OCTOBER 2024

D-V03 (NP)

 

Signalment (JPC #1803015): 6-day-old puppy 

 

HISTORY: This puppy presented with severe diarrhea. The puppy had been inoculated orally with an infectious agent 2 days previously.

 

HISTOPATHOLOGIC DESCRIPTION: Small intestine: Diffusely, the mucosal villus:crypt ratio is decreased to 1:1 (villar blunting), there is focally extensive villar fusion, and the villi are multifocally lined either by attenuated to vacuolated enterocytes or less often by small amounts of eosinophilic cellular and basophilic karyorrhectic debris (necrosis) admixed with few intact and necrotic neutrophils. Within the crypts, enterocytes have a high nuclear:cytoplasmic ratio with large, vesiculate nuclei and prominent nucleoli and they frequently pile up to 3 cells thick with increased mitotic activity (crypt hyperplasia). The lamina propria is diffusely and mildly expanded by few lymphocytes and histiocytes with fewer neutrophils and there is mild vascular congestion, most prominent within the apical aspect of the villi.

 

MORPHOLOGIC DIAGNOSIS: Small intestine: Villus atrophy, blunting, and fusion, diffuse, marked, with enterocyte necrosis, mild lymphohistiocytic enteritis, and crypt hyperplasia, breed unspecified, canine.

 

ETIOLOGIC DIAGNOSIS: Coronaviral enteritis

 

CAUSE: Canine coronavirus (CCV; alphacoronavirus)

 

GENERAL DISCUSSION:

• Single-stranded, positive-sense, pleomorphic, RNA viruses; 60-200 nm diameter, enveloped, with widely spaced, club-shaped, radial, 20 nm long surface projections (peplomers) that resemble a solar corona
• As a group, coronaviruses generally cause enteric and respiratory disease
• Acid stable (beneficial for enteric survival), heat labile (typically more clinical disease in winter)
• Coronaviruses infecting each host species (wide range of wild and domestic animals, including birds) appear distinctive; some host species can be infected by more than one type of coronavirus; cross-infection can occur between host species
• Four genera: Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus

• Alpha and betacoronaviruses infect mammals
• Gamma and deltacoronaviruses affect birds with some mammalian spillover
• Many unclassified and undiscovered coronaviruses remain
• Three antigenic groups: I, II, and III
• Cross-reactivity occurs between coronaviruses in the same antigenic group
• Group I coronaviruses infect multiple species
• Canine coronavirus (CCoV)
• The canine alphacoronavirus is widely prevalent and typically causes a transient, nonfatal enteritis in puppies
• Pantropic canine coronavirus identified in Europe can cause fatal infections; typically occurs concurrently with canine parvovirus 2c
• The canine betacoronavirus is one of the etiologic agents of canine infectious respiratory disease (CIRD), with Bordetella bronchiseptica, Streptococcus zooepidemicus, Mycoplasma spp., canine adenovirus type 2, canine parainfluenza virus, canine herpesvirus 1, canine distemper virus (morbillivirus), reovirus and influenza viruses
  1. CcoV may be associated with more severe cases of CIRD (De Luca, J Vet Diagn Invest, 2023)

                        

PATHOGENESIS:

• Canine alphacoronavirus

• Ingestion (fecal/oral transmission from environmental contamination and fomites) à virus enters upper duodenal enterocytes along villar tips via viral spike protein interaction with host protein aminopeptidase (APN) (~2 days post infection; incubation period 1-4 days) à spreads caudally through the small intestine (infrequently can extend into large intestine) à viral replication occurs in cytoplasm à infected enterocytes undergo suspected viral-induced apoptosis and are shed into intestinal lumen à loss of enterocytes results in villus atrophy and fusion à malabsorptive diarrhea with loss of fluids/electrolytes (sodium, chloride, bicarbonate, and potassium) à dehydration and acidosis
• Viremia and systemic infection have not been documented with typical canine alphacoronaviral infection (excluding pantropic strain), but CCoV will spread locally to mesenteric lymph nodes, liver, and spleen
• Dogs shed virus for at least 2 weeks following infection

 

TYPICAL CLINICAL FINDINGS:

Enteric form (alphacoronavirus):

• Spreads rapidly; recovery within 7-10 days; low morbidity and mortality; deaths from dehydration or concurrent illness
• Subclinical disease to rapidly fatal gastroenteritis +/- vomiting; leukopenia not characteristic
• Clinical signs less severe, but more chronic/intermittent than with parvovirus

Pantropic form:

Respiratory form (betacoronavirus):

• Typically mild respiratory signs that may become complicated by association with other agents of canine infectious respiratory disease (CIRD)
• Severe cases may present with lethargy, inappetence, vomiting, hemorrhagic diarrhea, and neurologic signs

 

TYPICAL GROSS FINDINGS:

• Mortality is typically low and necropsies are infrequent; the small intestinal mucosa and mesenteric lymph nodes may be congested
• Dilated intestinal loops are filled with watery, yellow-green feces

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Villus blunting and fusion 
• Deepening of intestinal crypts 
• Vacuolation of apical enterocytes 

 

ULTRASTRUCTURAL FINDINGS:

 

ADDITIONAL DIAGNOSTIC TESTS:

• Electron microscopy
• ELISA tests
• PCR: NanoPCR is effective for detecting CCV1, CCV2, or mixed infections (Qin, J Vet Diagn Invest, 2021)

 

DIFFERENTIAL DIAGNOSIS: 

• Canine parvovirus: Clinical signs more severe, crypt necrosis, hemorrhage, severe leukopenia
• Rotavirus: Histologic lesions very similar; however, coronavirus tends to have more crypt abscesses and crypt hyperplasia than rotavirus; clinical disease mild; diarrhea not seen in dogs > 6 months or in puppies that received colostrum

 

COMPARATIVE PATHOLOGY:

Table of common coronaviruses and their associated lesions (excerpted from Kenney, et al. 2021 with additional lagomorph and mustelid coronaviruses):

 

Alphacoronaviruses
Feline CoV	Feline	Gastroenteritis and diarrhea
Feline infectious peritonitis virus (FIP)	Feline	Peritonitis, pneumonia, meningoencephalitis, panophthalmitis; granulomatous phlebitis
Canine CoV	Canine	Gastroenteritis and diarrhea; uncommonly severe enteritis and leukopenia
Transmissible gastroenteritis virus (TGEV)	Porcine	Gastroenteritis; watery diarrhea, vomiting, dehydration
Porcine respiratory CoV	Porcine	Subclinical to mild respiratory disease
Porcine epidemic diarrhea virus (PEDV)	Porcine	Gastroenteritis; watery diarrhea, vomiting, dehydration (western Europe; similar to TGE)
Swine acute diarrhea syndrome (SADS)-CoV	Porcine	Gastroenteritis; watery diarrhea, vomiting, dehydration
Epizootic catarrhal enteritis (ECE)	Ferrets	Profuse, green mucoid diarrhea in adults; thought to be a coronavirus
Systemic Coronavirus-Associated Disease	Ferrets	Pyogranulomatous inflammation similar to FIP in cats within numerous organs
Betacoronaviruses
Porcine hemagglutinating encephalomyelitis virus (PHEV)	Porcine	Vomiting, wasting, encephalomyelitis; anorexia, hyperesthesia, muscle tremors, emaciation (usually no diarrhea)
Mouse hepatitis virus (MHV)	Mouse	Hepatic necrosis, enteritis, demyelinating encephalomyelitis; syncytia formation
Rat CoV/sialodacryoadenitis virus	Rat	Sialodacryoadenitis, porphyrin released from damaged harderian gland, squamous metaplasia of ducts; rhinitis, pneumonia
Bovine CoV (winter dysentery)	Bovine	Gastroenteritis with profuse or bloody diarrhea, dehydration, decreased milk production; respiratory disease
Equine CoV	Equine	Gastroenteritis
Canine respiratory CoV	Canine	Typically mild respiratory disease
Severe acute respiratory syndrome (SARS) CoV	Humans; NHP	Respiratory disease (bats and civet cats - natural reservoir; civets may also serve as an amplification host); NHP and humans develop multifocal hepatitis and mild diffuse colitis
Middle East respiratory syndrome (MERS) CoV	Humans	Respiratory disease (bats and dromedary - camels natural reservoir)
COVID-19 SARS-CoV-2	Humans, other species	Respiratory disease (bats/unknown – natural reservoir)
Rabbit enteric coronavirus	Rabbits	Enteritis, dehydration and emaciation
Gammacoronaviruses
Avian infectious bronchitis virus	Chickens	Tracheobronchitis, nephritis, decreased egg production
Bluecomb virus (Turkey CoV)	Turkeys	Enteritis, diarrhea, depression, cyanotic comb
Deltacoronaviruses
Porcine deltacoronavirus (PDCoV)	Porcine	Gastroenteritis in sows and nursing pigs; low mortality in nursing pigs; clinically indistinguishable from TGEV and PEDV
Pleural effusion disease virus	Rabbits	Multifocal myocardial degeneration and necrosis (no evidence that causative agent occurs as a natural pathogen)

 

 

REFERENCES:

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2. Church ME, Terio KA, Keel MK. Procyonidae, Viverridae, Hyenidae, Herpestidae, Eupleridae, and Prionodontidae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:305, 310, 312.
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4. De Luca E, Álvarez-Narváez S, Baptista RP, Maboni G, Blas-Machado U, Sanchez S. Epidemiologic investigation and genetic characterization of canine respiratory coronavirus in the Southeastern United States. J Vet Diagn Invest. 2024;36(1):46-55.
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