An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, Hubei Province, China, has spread rapidly to multiple countries, causing a public health crisis. [1, 2] Many studies have confirmed that SARS-CoV-2 infections can cause multiple organ damage. The lungs, heart, kidney, immune system and coagulation system are common targets of SARS-CoV-2. [3, 4] It has been reported that COVID-19 can be combined with pancreatic injury. [5, 6] Recently, some reports of COVID-19-associated acute pancreatitis have been published in the literatures. [7, 8] However, onset with acute pancreatitis in COVID-19 patients has not been reported. We describe two cases of COVID-19 with acute pancreatitis as the initial manifestation.
A 42-year-old male was admitted on 28 February 2020 with a history of nausea and persistent upper abdominal pain with radiation to the back for three days. He did not complain of fever, cough, fatigue, or diarrhea. He denied drinking, taking medicine, or overeating in recent days.
He had no history of gallstone or autoimmune disease. Abdomen computed tomography (CT) on 28 February (day 3 of illness) revealed prominence of the pancreas and peripancreatic fluid accumulation, without biliary dilatation or microlithiasis. Both amylase and lipase in the blood were increased, with values of 132 U/L (reference, 0-180 U/L) and 382 U/L (reference, 0-180 U/L), respectively. Initial liver biochemical tests showed that transaminase, bilirubin, and albumin were normal. Serum calcium and triglyceride levels were 1.96 mmol/L (reference, 2.11-2.52 mmol/L) and 3.2 mmol/L (reference, <1.7 mmol/L), respectively. The 
In this study, we described two patients with COVID-19 who initially presented with persistent upper abdominal pain and nausea and were diagnosed with acute pancreatitis.
Alternative etiologies for pancreatitis, including medication, gallstones, alcohol, autoimmune or other, more common etiologies, were ruled out in these two patients. Patient one died of circulatory and acute renal failure. The second patient was discharged after showing significant improvement. Wang et al. reported that the incidence of pancreatic injury was 17% in patients with COVID-19 pneumonia, but they did not find any patients with acute pancreatitis. [5] Amer et al reported two patients who were diagnosed with acute pancreatitis associated with SARS-CoV-2. [7] Autopsy revealed that SARS-CoV-2 was detected in the tissues of the lung, liver, and heart, but whether the virus invades the pancreas is still unclear. [9] A spike protein encoded by the coronaviral genome is responsible for facilitating the entry of the CoV into the target cell; analysis of the receptor-binding motif in the spike protein shows that most of the amino acid residues essential for receptor binding are conserved between SARS-CoV and SARS-CoV-2, suggesting that SARS-CoV-2 uses the same cell entry receptor, angiotensin converting enzyme II (ACE2). [10, 11] SARS-CoV has been detected not only in the tissues of the lung, liver, stomach, and kidney but also in the pancreas, indicating that the pancreas is a potential coronaviral target. [12] ACE2 is highly expressed in the pancreas, and SARS-CoV enters the islets using ACE2 as its receptor and damages them, causing acute A c c e p t e d M a n u s c r i p t diabetes. [13] It has been reported that viral infection or immune factors are a rare cause of pancreatitis. [14, 15] This evidence suggests that coronavirus may directly cause pancreatic injury. Whether pancreatic injury is secondarily caused by hypoxia or immune damage secondary to the systemic inflammatory response is unclear.
Notably, the number of T cells in peripheral blood was decreased in these two patients. A reduction of T cells is common in severe COVID-19, indicating that the novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. [16] The T cell count was extremely low in patient one after COVID-19 infection, and the patient died despite maximal mechanical ventilatory support and circulation support. A low T cell count may be a surrogate for poor clinical outcomes.
Clinical data on COVID-19 with pancreatic injury are very limited. We reported two COVID-19 patients who initially presented with acute pancreatitis with different outcomes.
Low T cells may indicate a poor outcome. The pathogenesis of acute pancreatitis caused by SARS-CoV-2 requires further research.
Written informed consent was obtained from patient or legal representative. Ethical approval was granted by the ethics board of the Institute of People's Hospital of Wuhan University (WDRY2020-K068).
This work was supported by the National Key Development Plan for Precision Medicine M a n u s c r i p t 