Signalment: (JPC# 1782647): Two-day-old piglet

HISTORY: This piglet had profuse, watery feces and vomited milk curd.

HISTOPATHOLOGIC DESCRIPTION:

Small intestine: Diffusely and circumferentially the intestinal wall is thin due to a loss of normal intestinal mucosal architecture characterized by villi that are severely blunted, shortened, and fused as well as marked crypt loss, reducing the villus height to crypt depth ratio to less than 1:1. The mucosal lining is reduced to a single layer of attenuated basophilic enterocytes, and remaining crypts are lined by either flattened, attenuated epithelium or hypertrophic epithelial cells that occasionally pile up and contain a moderate amount of foamy basophilic cytoplasm and a large, irregularly ovoid nucleus with finely stippled chromatin and one prominent nucleolus, and there are occasional mitotic figures (regeneration). Multifocally, remaining crypt lumina contain small amounts of eosinophilic cellular and karyorrhectic debris (necrosis) and few macrophages, lymphocytes, and plasma cells (crypt abscesses). Diffusely, the lamina propria is moderately expanded by lymphocytes and plasma cells. The intestinal lumen is dilated.

Mesentery: Perimeter vascular plexus (perimesenteric plexus) is present (normal porcine structure).

MORPHOLOGIC DIAGNOSIS: Small intestine: Villar necrosis and loss, diffuse, acute, severe, with multifocal crypt regeneration and crypt abscesses, breed unspecified, porcine.

ETIOLOGY: Porcine coronavirus (alphacoronavirus 1)

ETIOLOGIC DIAGNOSIS: Coronaviral enteritis

CONDITION: Transmissible gastroenteritis (TGE)

GENERAL DISCUSSION:

Coronaviruses are enveloped, ssRNA viruses that infect a diverse host range including birds and mammals and typically presents as mild to severe respiratory or enteric disease; divided into 4 genera: Alpha-, Beta-, Gamma-, and Deltacoronavirus
Gastrointestinal coronaviruses in pigs include:
1. Alphacoronavirus: Porcine epidemic diarrhea virus (PEDV), Transmissible gastroenteritis virus (TGEV)
2. Betacoronavirus: Porcine hemagglutinating encephalomyelitis virus (PHEV)
3. Deltacoronavirus: Porcine deltacoronavirus (PDCoV, SDCV)
TGE is a highly contagious disease in piglets <10-14 days of age characterized by near 100% morbidity, vomiting and profuse diarrhea
1. It may cause diarrhea and villous blunting in susceptible pigs of all ages, although the youngest are most severely affected (i.e. neonates, nursing/suckling) and severity of clinical signs decreases with age, mild or in apparent signs in sows
2. Seasonal, usually winter and spring; also seems to affect chilled piglets, likely due to viral sensitivity to warmth and sunlight

PATHOGENESIS:

Virus ingestion (feces-contaminated fomites or direct contact) -> Infection of villous epithelial cells -> Lysis of epithelial cells -> Unable to digest carbohydrate -> Decreased absorption and digestion -> Osmotic diarrhea
1. Viral attachment and entry
  - S protein is a viral envelope attachment protein used to bind to sialic acid in mucin then later to aminopeptidase N on the apical surfaces of enterocytes only in the tip and sides of villi
  - E2 is another envelope protein that facilitates enterocyte entry
2. Viral reproduction and escape: Leads to cell lysis (basement membranes are intact) -> Collapse (atrophy) of the villus
3. Denuded villi allows for absorption of endotoxins/other potentially harmful molecules -> Systemic cardiovascular and hemodynamic effects
4. Malabsorption osmotic diarrhea: Enterocyte loss -> Unable to digest carbohydrates -> Increased fermentation by resident bacteria (maldigestion) -> Osmotic gradient that draws fluid into the lumen
Regeneration/Repair
1. Virus does not infect undifferentiated cells of the crypts -> Crypt epithelium proliferates -> Flattened enterocytes migrate up and line shortened villi -> Mature into columnar enterocytes
Several mechanisms account for the age-dependent susceptibility to TGE:
1. Neonates:
  - Have tall villi (villus height:crypt depth is 7-9:1) lined by mature differentiated enterocytes and short, inactive crypts of undifferentiated epithelium > large population of susceptible cells and crypts that are slow to repair
  - Inherently susceptible to dehydration, electrolyte imbalances, hypoglycemia
2. Piglets >3 weeks are more resistant due to:
  - Virus production in enterocytes of older pigs is less efficient, possibly due to the onset of the immune response or the inability of these regenerating cells to support virus growth
  - Crypt epithelium is actively proliferative (injured mucosa can regenerate faster)

TYPICAL CLINICAL FINDINGS:

< 2 weeks of age (suckling piglets)
1. Vomiting and profuse yellow watery diarrhea (odoriferous, contains undigested milk); rapid weight loss
2. Pronounced dehydration, hypoglycemia, metabolic acidosis
3. Near 100% mortality within 2-5 days
>2 weeks of age
1. Transient vomiting and diarrhea
2. Dehydration, unthrifty condition
3. Likely to recover
Feeder pigs and sows
1. Inapparent or mild fever, inappetence, diarrhea
2. Agalactia in affected sows

TYPICAL GROSS FINDINGS:

External: Dehydration, perineum stained with fluid feces
Stomach: May contain milk curd
Small intestine: Flaccid, walls thin and transparent, distended with gas and yellow frothy fluid with flecks of mucus
1. Lesions may be patchy and are most common in the middle and lower small intestine

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Small intestinal severe villus epithelial cell loss with villus atrophy/blunting (leading to a marked decrease in villus height:crypt depth) and fusion of adjacent villi
1. Lesion severity is a function of age and disease stage
Hypertrophy of crypts (prominent regeneration)
Mixed submucosal inflammatory cell infiltrate if secondary invaders are present

ADDITIONAL DIAGNOSTIC TESTS:

Immunofluorescence (IFA) or immunoperoxidase staining
PCR (e.g. oral fluids, feces, and fecal swabs)
1. Work is being done on standardization and increased communication between state veterinary diagnostic laboratories for monitoring enteric coronaviruses (Trevisan, J Vet Diagn Invest. 2021)
Virus isolation
Serology

DIFFERENTIAL DIAGNOSIS:

For diarrhea in piglets; note age of piglet affected

Porcine epidemic diarrhea (PEDV) (Alphacoronavirus)
1. Most severe in suckling (or naïve) pigs (nearing 100% mortality), but typically milder than TGE
2. Clinically, grossly, and histologically indistinguishable from TGE (additional diagnostics required)
3. Histology: Small intestinal villus atrophy with occasional epithelial syncytia
E. coli (enteric colibacillosis) (D-B13)
1. Profuse diarrhea in piglets < 10 days of age (peak incidence at 3 days of age)
2. No vomiting, may have mild villous atrophy
3. Presence of bacilli adherent to brush border of enterocytes
Rotavirus enteritis (D-V07, V08)
1. Disease in suckling and weaned pigs (1-5 weeks of age)
2. High morbidity and low mortality
3. Villous atrophy less severe than in TGE
Clostridium perfringens type C (clostridial enterotoxemia) (D-B02)
1. Affects newborn piglets less than one week of age
2. Bloody diarrhea, mucosal hemorrhage and necrosis, rapid death
Hemagglutinating encephalomyelitis virus (Betacoronavirus):
1. Affects piglets <10 days of age
2. Vomiting is characteristic; wasting disease; acute encephalomyelitis may occur
3. Diarrhea may occur but is not severe
Coccidiosis (Isospora suis) (D-P01)
1. Diarrhea without blood in piglets 5-15 days of age (peak incidence 7-10 days of age)
2. Clinical signs precede production of oocysts.
Porcine Deltacoronavirus
1. Diarrhea and vomiting in all age groups, mortality in young piglets
2. Similar to PEDV and TGE but distinguishable

COMPARATIVE PATHOLOGY:

Selected coronaviruses (adapted from Kennedy, Vet Pathol. 2021):

Alphacoronavirus

Canine coronavirus (D-V03): Gastroenteritis and diarrhea; less frequently, severe enteritis and leukopenia
Porcine respiratory coronavirus: Mild respiratory disease or subclinical
Porcine epidemic diarrhea virus (PEDV) (D-V06): Gastroenteritis; watery diarrhea, vomiting, dehydration
Feline enteric coronavirus (FeCoV); Feline infectious peritonitis virus (FIPV) (S-V03, U-V06, P-V15): FeCoV: Mild to moderate gastroenteritis and diarrhea, especially in kittens; FIPV: Peritonitis, pneumonia, meningoencephalitis, panophthalmitis
1. Reported in domestic and non-domestic felids
Epizootic catarrhal enteritis of ferrets (ECE): A highly contagious diarrheal disease of ferrets with high morbidity and low mortality
Epizootic catarrhal gastritis in mink

Betacoronavirus

Porcine hemagglutinating encephalomyelitis virus: Vomiting, wasting, encephalomyelitis
Mouse hepatitis virus (lethal intestinal virus of infant mice [LIVIM]) (D-V04): Hepatitis, enteritis, encephalomyelitis
1. May be hepatotropic or polytropic, affecting a variety of organs
Sialodacryoadenitis virus in rats (D-V05, S-V02): Necrosis of salivary and nasolacrimal glands
Bovine coronavirus (“Winter Dysentery”): Gastroenteritis with profuse or bloody diarrhea, dehydration, decreased milk production, or respiratory disease
Equine coronavirus: Gastroenteritis
Canine respiratory coronavirus: Respiratory disease
Severe acute respiratory syndrome (SARS) CoV: Respiratory disease; zoonotic with bats and civet cats as natural reservoir
COVID-19 SARS-CoV-2: Respiratory disease; zoonotic with bats/unknown natural reservoir
Middle Eastern Respiratory Syndrome (MERS): Respiratory disease; zoonotic with bats and dromedary camels as natural reservoir
Rabbit Enteric Coronavirus: Transient and mild diarrhea with villus blunting and enterocyte necrosis, especially in young rabbits (3-10 wks of age)

Gammacoronavirus

Avian infectious bronchitis virus (IBV): Tracheobronchitis, nephritis, decreased egg production
Turkey coronavirus (Bluecomb virus of turkeys): Enteritis, cyanosis of skin of head and neck

Deltacoronavirus

Porcine Deltacoronavirus

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