SARS-CoV-2 induced necrotizing pancreatitis

Dear Editor,

Acute pancreatitis diagnosis is a combination of clinical, laboratory and imaging findings. Common etiologies are alcohol, biliary obstruction/gall stones, drugs, trauma, and severe hypertriglyceridemia. While viral pancreatitis by HIV (human immunodeficiency virus), Cytomegalovirus, Coxsackievirus B, EBV (Epstein-Barr virus), Mumps and Influenza A (H1N1) has been reported, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced pancreatitis was rarely reported in the literature. We here-below present such a case.

A 62-year-old male presented to the Emergency Department complaining of shortness of breath at rest, watery diarrhea, vomiting and associated decrease in oral intake of two weeks’ duration. His past medical history is significant for hypertension, type 2 diabetes mellitus and end stage renal disease status post kidney transplant four years ago.

Vital signs, including temperature, were within normal range. Physical exam was unremarkable except for decreased bilateral air entry. Initial blood tests were only suggestive of mild leukopenia with a white blood cell count (WBC) of 3600/cu.mm (reference range 4000–11,000/cu.mm) and acute kidney injury with creatinine level of 2.3 mg/dL compared to a baseline of 1.9 mg/dL (normal range). C-reactive peptide (CRP) was 58 mg/L (reference range 0–2.5 mg/L) and pro-calcitonin level was 0.2 ng/mL (reference range <0.05 ng/mL). Patient tested positive for SARS-CoV-2 on polymerase chain reaction (PCR). The patient was admitted to the SARS-CoV-2 unit at our institution.

On the second day, he reported severe epigastric pain radiating to the back. Physical exam revealed a soft abdomen with epigastric tenderness. Laboratory tests were significant for elevated lipase levels reaching 4361 U/L (reference range 13–60 U/L). Thus, the diagnosis of acute pancreatitis was made.

On further history, patient denied trauma, alcohol or steroid intake, scorpion sting, recent endoscopic retrograde cholangiopancreatography (ERCP) or previous pancreatitis. Medications were carefully reviewed with none associated with pancreatitis except for saxagliptin in less than one percent of cases. Saxagliptin was thus discontinued. Abdominal ultrasound showed no acute finding of cholelithiasis or cholecystitis, with no evidence of gallstones. Triglyceride level and liver function tests were unremarkable.

Epigastric pain failed to improve a week later despite treatment with perfalgan, hydration and cessation of saxagliptin. Resonance imaging (MRI) of the abdomen with gadolinium was positive for acute necrotizing pancreatitis involving the peripancreatic tissue with an acute necrotic collection supero-anterior to the pancreatic tail.

In the setting of worsening inflammatory markers, we opted to empirically treat with meropenem for a total of 6 days without CT-guided fine needle aspiration.

At the end of the antibiotic course, inflammatory markers trended down and epigastric pain resolved. By exclusion, and since the patient worsened despite cessation of saxagliptin, SARS-CoV-2 was attributed as a cause of the acute necrotizing pancreatitis.

SARS-CoV-2 induced pancreatitis was rarely described in case reports. Wang et al. reported mild pancreatic injury in 17% of patients with SARS-CoV-2 pneumonia. This was attributed to either direct viral involvement of the pancreas, or secondary to severe illness without substantial pancreatic injury.¹ In a large cohort study, Inamdar et al. showed a low prevalent association between SARS-CoV-2 and acute pancreatitis with a 0.43% incidence compared to 0.27% in patients without SARS-CoV-2.² As per the authors, the etiology of pancreatitis was undetermined in a significant proportion of SARS-CoV-2 patients.

The pathogenesis of SARS-CoV-2 induced pancreatic injury is thought to be related to the increased expression of angiotensin converting enzyme-2 (ACE-2) in the pancreatic islet cells of affected individuals.³ SARS-CoV-2 has high binding affinity to transmembrane ACE-2 and uses a wide array of host proteases include transmembrane protease serine 2 (TMPRSS2) to facilitate cell entry following receptor binding.⁴ ACE-2 mediated anti-oxidant, anti-hypertrophic and vasodilatory effects are lost following endocytosis to the enzyme along with SARS-CoV-2. In a cohort of SARS-CoV-2 patients, circulating angiotensin II (pro-inflammatory mediator) levels were markedly elevated compared to healthy control and markedly correlated to the viral load.⁵ Indeed, ischemia, inflammation and pancreatic edema induced by SARS-CoV-2 ACE-2 blockade could be the culprits of this entity.

In conclusion, SARS-CoV-2 is a newly described cause of acute necrotizing pancreatitis. Given the overall low prevalence of pancreatitis compared to other gastrointestinal manifestations, this entity has mainly been reported in case reports. We suggest including pancreatitis in the list of SARS-CoV-2 gastrointestinal complications.