COVID-19-associated gastrointestinal and liver injury: clinical features and potential mechanisms

Abstract

Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is spreading globally and poses a huge threat to human health. Besides common respiratory symptoms, some patients with COVID-19 experience gastrointestinal symptoms, such as diarrhea, nausea, vomiting, and loss of appetite. SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2 (ACE2) and there is increasing evidence of a possible fecal–oral transmission route. In addition, there exist multiple abnormalities in liver enzymes. COVID-19-related liver injury may be due to drug-induced liver injury, systemic inflammatory reaction, and hypoxia–ischemia reperfusion injury. The direct toxic attack of SARS-CoV-2 on the liver is still questionable. This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.

Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications

“…In support, intra-gastric inoculation of SARS-CoV-2 in a mouse model expressing human ACE2 caused productive infection and most interestingly led to pulmonary pathological changes [ 40 ]. A significant association between liver dysfunction and mortality of COVID-19 patients has been also reported [ 41 , 42 ], which may relate to direct viral infection (still questionable due to relatively low ACE2 expression levels in the liver [ 17 ]); to indirect damage because of drug-induced liver injury or because of COVID-19-triggered systemic inflammation [ 43 ]. Analyses of severe COVID-19-induced biochemical alterations in the liver have shown the elevation of liver enzymes, such as alanine aminotransferases and aspartate aminotransferases, and significantly lower albumin levels [ 43 , 44 ] and thus, liver markers should be monitored continuously during COVID-19 evolvement.…”

“…A significant association between liver dysfunction and mortality of COVID-19 patients has been also reported [ 41 , 42 ], which may relate to direct viral infection (still questionable due to relatively low ACE2 expression levels in the liver [ 17 ]); to indirect damage because of drug-induced liver injury or because of COVID-19-triggered systemic inflammation [ 43 ]. Analyses of severe COVID-19-induced biochemical alterations in the liver have shown the elevation of liver enzymes, such as alanine aminotransferases and aspartate aminotransferases, and significantly lower albumin levels [ 43 , 44 ] and thus, liver markers should be monitored continuously during COVID-19 evolvement. ACE2 and TMPRSS2 are highly expressed in gallbladder [ 17 ], whereas regarding pancreas ACE2 is expressed in exocrine tissue microvasculature and in a subset of pancreatic ducts with TMPRSS2 expression being restricted to ductal cells [ 45 , 46 ].…”

“…The molecular pathways involved in SARS-CoV-2 infection in human (e.g., lung) cells are depicted in Fig. 1 relate to direct viral infection (still questionable due to relatively low ACE2 expression levels in the liver [17]); to indirect damage because of drug-induced liver injury or because of COVID-19-triggered systemic inflammation [43]. Analyses of severe COVID-19-induced biochemical alterations in the liver have shown the elevation of liver enzymes, such as alanine aminotransferases and aspartate aminotransferases, and significantly lower albumin levels [43,44] and thus, liver markers should be monitored continuously during COVID-19 evolvement.…”

Delayed discharge is associated with higher complement C3 levels and a longer nucleic acid-negative conversion time in patients with COVID-19

“…In this study, only one critically ill patient required tracheotomy and ventilator support. Similarly, this patient had diarrhea, indicating that patients with COVID-19 with diarrhea need ventilator support and intensive care more often than those without diarrhea 22 . The presence of gastrointestinal symptoms is associated with a higher risk of hospitalization, which becomes more pronounced as the severity of the disease increases 23 , 24 .…”

Impact of the 2019 Novel Coronavirus Disease (COVID-19) Epidemic on Radiotherapy-Treated Patients with Cancer: A Single-Center Descriptive Study

“…COVID-19 is a systemic disease caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV -2), which is most notable for causing substantial respiratory pathology. 9 The clinical symptoms of COVID-19 are primarily fatigue, fever, cough and shortness of breath. Some patients with severe disease have life-threatening multiple failures, such as myocardial dysfunction, acute kidney injury, hepatocellular injury, hyperglycemia and ketosis.…”