SARS-CoV
Gastrointestinal (GI) involvement in SARS-CoV was common and occurred at different stages of the disease; rarely, patients reported only GI symptoms.68, 69, 70 The most common GI presentation was loss of appetite (up to 55%) and watery diarrhea (up to 76%)69 , 71 (Table 3 ). Patients also complained of nausea, vomiting (14-22.2%) and abdominal pain (3.5-12.6%).72 The association between symptoms and outcomes had been mixed. Leung et al found that patients with diarrhea had a higher likelihood of requiring ICU admission and ventilatory support.68 Others found that GI symptoms at presentation conferred a better prognosis.69 Others found no association between diarrhea and the development of ARDS or the requirement of ventilatory support.70 The mechanism of GI symptoms is unclear, but SARS-CoV particles have been detected in saliva (100%), feces (97%) and mucosal epithelial and lymphoid tissue of affected patients with associated depletion of lymphoid tissue.72
Table 3 Hepatobiliary manifestation of SARS-CoV, MERS-CoV and COVID-19.
SARS (only studies with large study population included)
Study Duan et al (2003)N = 154, confirmed casesRetrospective study Ding et al (2004)N = 8 (4 confirmed cases, 4 control)Clinicopathologic study Chau et al (2004)N = 3, confirmedCase report Zhao et al (2004)N = 169, confirmed casesRetrospective study Yang et al (2005)N = 168, confirmed casesRetrospective study Zhan et al (2006)N = 12 (6 confirmed cases, 6 controls)Clinicopathologic study Yang et al (2010)N = 539 (520 confirmed cases)Prospective study
Clinical Features Hepatic dysfunction Hepatic dysfunction Hepatic dysfunction Hepatic dysfunction Hepatic dysfunction Diabetes:• 35.9% within 3 days
• 51.3% within 2 weeks
Key findings on investigations • ↑ALT &/or AST (37.7%)
• ↑ALT (70.7%)
• ↑ALT and AST (22.4%)
• ALT and AST normalized within 2 weeks in 75.9%
• ↑T. bili (8.4%)
• ↑Albumin (24%)
• ↓ Prealbumin (28.6%) • ↑ ALT
• + viral RT-PCR in liver, not sera • ↑ ALT (32.76-62.50%)
• ↑ AST (13.04-40.00%)
• ↓ Albumin (40.35-72.00%)
• Total protein remained normal ↑ ALT:• Peak: 111.32 ± 160.24 U/L
• At admission: 52.5%,
• First week: 71.8%
• Second week: 85.7%
• Third week: 85.2%
• ↓ Albumin ↑ blood glucose
Histopathology N/A • Virus detected in liver, pancreas
• Virus not detected in spleen. • Apoptosis (3/3)
• Accumulated cells in mitosis (2/3)
• Ballooning hepatocytes
• Mild to moderate lobular lymphocytic infiltration
• Ki-67 + nuclei (0.5-11.4%)
• Virus detected in liver by RT-PCR, but not by EM N/A Nonspecific inflammation Spleen:• Severe white pulp damage
• Altered cell distribution
• Markedly reduced or absent CD3+, CD4+, and CD8+ cells
• CD68+ macrophages most numerous ACE2 receptors found in pancreatic islet cells
Key study findings and message • AST/ALT elevation rates associated with disease severity (P < 0.05)
• Possibly beneficial to suppress cytokine storm in early stage Liver may also be target of infection besides lungs Liver damage likely by virus directly Total protein remained normal despite albuminemia • No association found between liver damage, and oxygen saturation or degree of fever or immune dysfunction
• Liver damage likely by virus directly
• Hepatotoxic drugs may contribute • Spleen damage most likely due to direct viral attack
• Steroid medication may contribute
• Indirect viral mechanism, perhaps vascular, causing spleen injury • Higher mortality in patients with hyperglycemia, ↑ AST (P < 0.0001)
• Mortality not higher in patients with ↑ ALT (P = 0.35)
• SARS-CoV may cause acute insulin dependent diabetes mellitus
• 5% (2/39) still had diabetes 3 years after discharge
MERS
Study Saad et al (2014)N = 70, confirmed casesRetrospective Al-Hameed et al (2016)N = 8, confirmed casesProspective study Alsaad et al (2017)N = 1, confirmed casesClinicopathologic
Clinical Features Hepatic dysfunction (31.4%) Hepatic dysfunction later during ICU stay (62.5%) N/A
Key findings on investigations • ↓ Albumin
• ↑ AST
• ↑ T.bil • ↑ AST, ALT
• ↑ T.bil N/A
Histopathology N/A N/A Liver:• Mild portal inflammation, chronic, with CD4+ and CD8+ T lymphocytes. Necroinflammatory foci in hepatic lobules
• Reactive parenchyma with mild hydropic degeneration, more in perivenular area
• Rare multinucleated hepatocytes
• Mild disarray of the hepatic plates
• Minimal macrovesicular perivenular steatotic change, sinusoidal congestion, hemorrhage and focal perivenular hepatocytes loss
Key study findings and message Albumin <35 g/L at diagnosis predictor of severe infection (P = 0.026) 41% developed multiorgan failure Portal and lobular hepatitis, viral particles not identified in liver on EM
COVID-19
Study Fan et al (2020)N = 148, confirmed casesRetrospective study Chai et al (2020)N = 4 (healthy)Clinicopathologic Huang et al (2020)N = 41, confirmed casesRetrospective study Wang et al (2020)N = 138, confirmed casesRetrospective study
Clinical features Hepatic dysfunction at admission (50.7%) Preexisting chronic liver disease (2%) Pre-existing chronic liver disease (2.9%)
Key findings on investigations ↓ CD4+ and CD8+ T cells in patients with hepatic dysfunction N/A ↑ AST (37%)(62% ICU, 25% non-ICU) ↑ LDH
Histopathology N/A ACE2 expression in cholangiocytes (59.7%) and hepatocytes (2.6%) N/A N/A
Key study findings and message • Patients with hepatic dysfunction more likely to have moderate-high fever, more in males (P = 0.035, 0.005)
• Abnormal liver function after admission associated with prolonged stay (P = 0.02) • Hepatic dysfunction more likely due to cholangiocyte damage by virus, not hepatocyte
• Drug induced damage, SIRS may also play a role Cytokine storm possible associated with disease severity AST, ALT, T.bil, LDH higher in ICU patients (P < 0.001, P = 0.007,P = 0.02, P < 0.001)
ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; MERS-CoV, middle east respiratory syndrome coronavirus; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-COV, severe acute respiratory syndrome coronavirus; T. Bili, total bilirubin.
A significant mode of spread in community outbreaks was fecal-oral transmission.70 , 73 , 74 Patients with diarrhea also had a higher rate of positive serological and nasopharyngeal secretion tests.75 The virus remained stable in stool up to 2-4 days, and may even be detectable as late as 4 weeks.70 , 73 , 76