PMC:7212949 / 28089-36793 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7212949","sourcedb":"PMC","sourceid":"7212949","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7212949","text":"GASTROINTESTINAL MANIFESTATIONS\n\nSARS-CoV\nGastrointestinal (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\nTable 3 Hepatobiliary manifestation of SARS-CoV, MERS-CoV and COVID-19.\nSARS (only studies with large study population included)\nStudy 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\nClinical Features Hepatic dysfunction Hepatic dysfunction Hepatic dysfunction Hepatic dysfunction Hepatic dysfunction Diabetes:• 35.9% within 3 days\n• 51.3% within 2 weeks\nKey findings on investigations • ↑ALT \u0026/or AST (37.7%)\n• ↑ALT (70.7%)\n• ↑ALT and AST (22.4%)\n• ALT and AST normalized within 2 weeks in 75.9%\n• ↑T. bili (8.4%)\n• ↑Albumin (24%)\n• ↓ Prealbumin (28.6%) • ↑ ALT\n• + viral RT-PCR in liver, not sera • ↑ ALT (32.76-62.50%)\n• ↑ AST (13.04-40.00%)\n• ↓ Albumin (40.35-72.00%)\n• Total protein remained normal ↑ ALT:• Peak: 111.32 ± 160.24 U/L\n• At admission: 52.5%,\n• First week: 71.8%\n• Second week: 85.7%\n• Third week: 85.2%\n• ↓ Albumin ↑ blood glucose\nHistopathology N/A • Virus detected in liver, pancreas\n• Virus not detected in spleen. • Apoptosis (3/3)\n• Accumulated cells in mitosis (2/3)\n• Ballooning hepatocytes\n• Mild to moderate lobular lymphocytic infiltration\n• Ki-67 + nuclei (0.5-11.4%)\n• Virus detected in liver by RT-PCR, but not by EM N/A Nonspecific inflammation Spleen:• Severe white pulp damage\n• Altered cell distribution\n• Markedly reduced or absent CD3+, CD4+, and CD8+ cells\n• CD68+ macrophages most numerous ACE2 receptors found in pancreatic islet cells\nKey study findings and message • AST/ALT elevation rates associated with disease severity (P \u003c 0.05)\n• 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\n• Liver damage likely by virus directly\n• Hepatotoxic drugs may contribute • Spleen damage most likely due to direct viral attack\n• Steroid medication may contribute\n• Indirect viral mechanism, perhaps vascular, causing spleen injury • Higher mortality in patients with hyperglycemia, ↑ AST (P \u003c 0.0001)\n• Mortality not higher in patients with ↑ ALT (P = 0.35)\n• SARS-CoV may cause acute insulin dependent diabetes mellitus\n• 5% (2/39) still had diabetes 3 years after discharge\nMERS\nStudy 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\nClinical Features Hepatic dysfunction (31.4%) Hepatic dysfunction later during ICU stay (62.5%) N/A\nKey findings on investigations • ↓ Albumin\n• ↑ AST\n• ↑ T.bil • ↑ AST, ALT\n• ↑ T.bil N/A\nHistopathology N/A N/A Liver:• Mild portal inflammation, chronic, with CD4+ and CD8+ T lymphocytes. Necroinflammatory foci in hepatic lobules\n• Reactive parenchyma with mild hydropic degeneration, more in perivenular area\n• Rare multinucleated hepatocytes\n• Mild disarray of the hepatic plates\n• Minimal macrovesicular perivenular steatotic change, sinusoidal congestion, hemorrhage and focal perivenular hepatocytes loss\nKey study findings and message Albumin \u003c35 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\nCOVID-19\nStudy 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\nClinical features Hepatic dysfunction at admission (50.7%) Preexisting chronic liver disease (2%) Pre-existing chronic liver disease (2.9%)\nKey findings on investigations ↓ CD4+ and CD8+ T cells in patients with hepatic dysfunction N/A ↑ AST (37%)(62% ICU, 25% non-ICU) ↑ LDH\nHistopathology N/A ACE2 expression in cholangiocytes (59.7%) and hepatocytes (2.6%) N/A N/A\nKey study findings and message • Patients with hepatic dysfunction more likely to have moderate-high fever, more in males (P = 0.035, 0.005)\n• Abnormal liver function after admission associated with prolonged stay (P = 0.02) • Hepatic dysfunction more likely due to cholangiocyte damage by virus, not hepatocyte\n• 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 \u003c 0.001, P = 0.007,P = 0.02, P \u003c 0.001)\nALT, 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.\nA 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\n\nMERS-CoV\nPatients may present with GI symptoms, pain and fever16 , 77 , 78 (Table 3). Patients with GI symptoms have delayed MERS-CoV serological clearance.60 , 79 MERS-CoV RNA in stool has been detected in about 15% of patients, much lower than SARS-CoV, and may not correlate with the presence of GI symptoms.79 , 80 While the virus replicates in the intestinal tract, isolation of the virus from feces and fecal-oral transmission are rare.81, 82, 83\n\nCOVID-19\nThere is increasing recognition of GI symptoms in COVID-19 patients (up to 50%).84 Patients may present only with GI symptoms.20 , 84 Loss of appetite and diarrhea have been the most commonly reported symptom (in up to 78.6% cases), and less often vomiting (up to 5%), and abdominal pain (up to 2%) (Table 3).20, 21, 22 , 84 Vomiting has been shown to be a more common presenting symptoms in children. The GI features seem to worsen with overall disease severity and the presence of abdominal pain has been associated with about 4 times higher odds of severe COVID.22 , 24 The delayed recognition of GI symptoms and lack of awareness may lead to a delay in seeking medical care.22 Patients who present later during their illness were more likely to suffer from hepatic dysfunction but without a difference in mortality, ICU days or time to discharge.22 Patients with obesity are at significantly higher risk for severe disease requiring critical care and invasive mechanical ventilation. Compared with patients with a BMI \u003c25 kg/m2, patients with BMI \u003e35 kg/m2 have been seen to have 7 times the odds for requiring invasive mechanical ventilation.25 , 26\nCOVID-19 virus enters enteric epithelial tissue through ACE 2 and transmembrane protease, serine 2, but the exact mechanism of GI symptoms is not known.85 The virus is detectable in stool in up to half of COVID-19 patients,86 , 87 and the feces remains positive for as much as 4 weeks.87 ACE 2 and viral protein have been detected in GI epithelial cells, and infectious virus particles were isolated from feces.88 Fecal polymerase chain reaction (PCR) testing has been shown to be as accurate as PCR detection from a sputum sample, and in some cases, fecal PCR is positive before sputum PCR.88 It remains unclear if the fecal-oral route is a significant mode of 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