Occam's razor or Hickam's dictum-COVID-19 is not a textbook aetiology of acute pancreatitis: a modified Naranjo score appraisal

Abstract

BACKGROUND: Acute pancreatitis (AP) is a disease spectrum ranging from mild to severe disease. During the coronavirus disease 2019 (COVID-19) pandemic, numerous reports of AP have been published, with most authors concluding a causal relationship between COVID-19 and AP. Retrospective case reports or small case series are unable to accurately determine the cause-effect relationship between COVID-19 and AP. AIM: To establish whether COVID-19 is a cause of AP using the modified Naranjo scoring system. METHODS: A systematic review was conducted on PubMed, World of Science and Embase for articles reporting COVID-19 and AP from inception to August 2021. Exclusion criteria were cases of AP which were not reported to be due to COVID-19 infection, age < 18 years old, review articles and retrospective cohort studies. The original 10-item Naranjo scoring system (total score 13) was devised to approximate the likelihood of a clinical presentation to be secondary to an adverse drug reaction. We modified the original scoring system into a 8-item modified Naranjo scoring system (total score 9) to determine the cause-effect relationship between COVID-19 and AP. A cumulative score was decided for each case presented in the included articles. Interpretation of the modified Naranjo scoring system is as follows: ≤ 3: Doubtful, 4-6: Possible, ≥ 7: Probable cause. RESULTS: The initial search resulted in 909 articles, with 740 articles after removal of duplicates. A total of 67 articles were included in the final analysis, with 76 patients which had AP reported to be due to COVID-19. The mean age was 47.8 (range 18-94) years. Majority of patients (73.3%) had ≤ 7 d between onset of COVID-19 infection and diagnosis of AP. There were only 45 (59.2%) patients who had adequate investigations to rule out common aetiologies (gallstones, choledocholithiasis, alcohol, hypertriglyceridemia, hypercalcemia and trauma) of AP. Immunoglobulin G4 testing was conducted in 9 (13.5%) patients to rule out autoimmune AP. Only 5 (6.6%) patients underwent endoscopic ultrasound and/or magnetic resonance cholangiopancreatogram to rule out occult microlithiasis, pancreatic malignancy and pancreas divisum. None of the patients had other recently diagnosed viral infections apart from COVID-19 infection, or underwent genetic testing to rule out hereditary AP. There were 32 (42.1%), 39 (51.3%) and 5 (6.6%) patients with doubtful, possible, and probable cause-effect relationship respectively between COVID-19 and AP. CONCLUSION: Current evidence is weak to establish a strong link between COVID-19 and AP. Investigations should be performed to rule out other causes of AP before establishing COVID-19 as an aetiology.