Although coronavirus disease 2019 (COVID-19) is mainly considered a lower respiratory tract infection, the disease can induce dysfunction in multiple organs, including the kidney, heart, liver, gut, and pancreas.1 Other viral diseases, such as human immunodeficiency virus, mumps, cytomegalovirus, coxsackievirus B and influenza A (H1N1), have been reported to cause acute pancreatic inflammation.2 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19 uses angiotensin-converting enzyme 2 (ACE2) receptors for invading the tissue cells and primarily spreads via the respiratory tract. The clinical signs of patients with COVID-19 usually include fever, cough, fatigue, and some patients have shown symptoms of gastrointestinal disturbance.3 However, acute liver injury in patients with COVID-19 is independently associated with adverse clinical outcomes.4 Little is known about the influence of SARS-CoV-2 in pancreatic injury. Herein this study discusses the current evidence for the effect of COVID-19 on pancreatic function.

Some associations between COVID-19 and acute pancreatitis have been reported. In a clinical study, two family members admitted to intensive care unit with COVID-19 were identified with acute pancreatitis.5 In one study in China, of 67 patients with severe COVID-19, 12 patients (17.9%) had elevated amylase levels, 11 patients (16.4%) had elevated lipase levels, and five patients (7.5%) had notable imaging features (focal enlargement of the pancreas or dilatation of the pancreatic duct).6 In addition, 2% of patients with non-severe COVID-19 had elevated lipase and amylase levels.6 In another study in China, elevated amylase levels were reported in 19 patients with COVID-19 admitted to the intensive care unit.7 In a cohort of 11 883 patients with COVID-19 in the United States, 32 patients met the criteria for a diagnosis of pancreatitis.8 In another study in the United States, 14 (18.7%) out of 75 patients with COVID-19 met the criteria for a diagnosis of acute pancreatitis.9 Although acute pancreatitis is rarely confirmed in patients with COVID-19, four cases of acute pancreatitis have been confirmed in different three studies after careful exclusion of other factors, highlighting a possible role of COVID-19 as an aetiological factor for acute viral pancreatitis.10 11 12

Elevated levels of pancreatic enzymes without clinical evidence of pancreatitis have been reported in patients with COVID-19.13 Patients with COVID-19 may experience symptoms associated with high pancreatic enzyme levels, such as gut inflammation, diabetes, and kidney diseases.14 Additionally, gastroenteritis is a well-known cause of elevated pancreatic enzymes15 and such elevation could be explained by raised intestinal permeability in response to inflammation, which promotes the reabsorption of macromolecules, such as amylase and lipase.16

In a study in China of 52 patients with COVID-19, nine (17.3%) patients had abnormal amylase or lipase levels, six of whom developed hyperglycaemia without pre-existing diabetes.17 Furthermore, SARS-CoV-2 infection of the surrounding exocrine pancreas can generate islet cell injury through the release of proinflammatory cytokines.18 Owing to the structural and syndromic similarities between SARS-CoV-2 and SARS-CoV, it is reasonable to consider evidence that SARS-CoV infection can destroy islets cells, leading to decreased insulin release: 3 years after recovery from SARS-CoV infection, up to 5% of patients develop diabetes.19 In three patients with COVID-19, Yao et al20 found that few pancreatic islet cells in the autopsy pancreas have degenerated with a normal exocrine pattern. Recently, a survey of 1122 hospitalised patients with COVID-19 indicated uncontrolled hyperglycaemia in 257 of them.21 Thus, similar to SARS-CoV infection, pancreatic injury may be associated with COVID-19 complications.

Autopsy reports from four patients with SARS-CoV infection identified SARS-CoV RNA in pancreatic tissues.22 Coronaviruses such as SARS-CoV and SARS-CoV-2 enter target cells via the ACE2 receptor. Therefore, expression of ACE2 in any organ may provide a pathway for SARS-CoV-2 infection leading to tissue injury.23 Notably, ACE2 is expressed in the exocrine glands and islets of the pancreas and the damage is proportional to the severity of SARS-CoV-2 infection.6 Abundant expression of ACE2 in human islets has been reported.23

In patients with severe COVID-19, the expression of ACE2 in the pancreas during SARS-CoV-2 infection can result in acute inflammation which caused acute pancreatitis.5 However, there are other possible causes of pancreatic injury in patients with COVID-19. Acute pancreatitis has also been reported as an adverse effect of lopinavir-ritonavir, a treatment for patients with COVID-19.24 Similarly, antipyretics, which the patient may have taken before admission, can cause pancreatic injury.17 A mild rise in blood pancreatic enzymes in patients with COVID-19 can also result from causes other than pancreatic damage.14

For intensive care unit clinicians making admission decisions, predicting the severity of acute pancreatitis is important. Validated scoring systems, including Ranson’s score, the updated Glasgow score, the harmless acute pancreatitis score, and the bedside index for severity of acute pancreatitis, have been used for predicting the severity and mortality of acute pancreatitis during presentation and admission. Among them, Ranson’s score diagnostic accuracy on admission is higher for prediction of severity, organ failure, and mortality based on receiver operator characteristic curves.25 26 These scoring systems may be used for predicting the severity and mortality of acute pancreatitis in patients with COVID-19.

Pancreatic dysfunction may be related to SARS-CoV-2 infection by direct invasion of the pancreatic cells or secondarily by tissue damage caused by the systemic inflammatory immune response or even by medication prescribed to treat severe cases of COVID-19. Clinicians should be aware of the possibility of pancreatic dysfunction in patients with COVID-19, and should take appropriate precautions if patients show relevant signs or symptoms.

The author contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. The author had full access to the data, contributed to the study, approved the final version for publication, and takes responsibility for its accuracy and integrity.

The author has disclosed no conflicts of interest.

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