Int J Gastrointest Interv 2023; 12(1): 22-28
Published online January 31, 2023 https://doi.org/10.18528/ijgii210060
Copyright © International Journal of Gastrointestinal Intervention.
Asad Ali Kerawala1,* , Bhagwan Das2 , Rabika Fatima3 , and Ahda Solangi4
1Department of Surgery, Cancer Foundation Hospital, Karachi, Pakistan
2Department of Endocrinology, Cancer Foundation Hospital, Karachi, Pakistan
3Department of Surgery, Dow University of Health Sciences, Karachi, Pakistan
4Department of Medicine, New York Medical College, Valhalla, NY, USA
Correspondence to:*Department of Surgery, Cancer Foundation Hospital, C-130, Block 09, Gulshan-e-Iqbal, Karachi 75500, Pakistan.
E-mail address: firstname.lastname@example.org (A.A. Kerawala).
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Originally thought to be a respiratory pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has been shown to cause a dizzying array of symptoms, including all major organ systems of the human body. As time elapsed, new strains of the virus have emerged, validating concerns about genetic mutation. No single treatment has proven beneficial in treating the consequences, and the world has been left at the mercy of this deadly pathogen. It has been proven that COVID-19 can cause strokes, myocardial infarcts, mesenteric infarcts, acute limb ischemia, and a wide array of other symptomatology. This review aimed to evaluate whether there exists an association between COVID-19 and pancreatitis. Forty publications (34 case reports and 4 case series) were included in the review. In total, 44 cases of acute pancreatitis (38 cases of acute edematous pancreatitis and 6 cases of necrotizing pancreatitis) in COVID-19 patients without any predisposing factors have been published since January 2020. Fortunately, only 4 (9.1%) of these patients were reported to have died. Although the exact mechanism by which COVID-19 causes pancreatitis is still unclear, studies so far have reported it as a multifactorial phenomenon. COVID-19 associated pancreatic injury is thought to involve direct cellular damage via local replication of SARS-CoV-2 within pancreatic cells, as they express angiotensin-converting enzyme 2 receptors even more strongly than lung cells. Our review concludes that acute pancreatitis should be kept in the differential list of all COVID-19 patients with gastrointestinal manifestations, especially in patients with acute abdomen.
Keywords: COVID-19, Necrotizing pancreatitis, Pancreatitis, SARS-CoV-2
The novel coronavirus (now officially named severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), the causative agent of coronavirus disease 2019 (COVID-19), emerged at the end of 2019 in Wuhan, a city in Hubei Province of China. The virus jumped hosts from bats to humans and engulfed the whole world, causing more than three million deaths.1 Originally thought to be a respiratory pathogen, SARS-CoV-2 has been shown to cause a dizzying array of symptoms including all major organ systems of the human body. As time elapsed, new strains have emerged, validating concerns about genetic mutation. No single treatment has proven beneficial in treating the consequences, and the world has been left at the mercy of this deadly pathogen. Initially, only symptomatic patients were tested and isolated. However, it quickly became evident that all contacts of the positive cases would also need to be tested, since many were found to have contracted the virus. Attempts at preparing a vaccine to bolster immunity started in mid-2020, and large-scale vaccination programs were implemented worldwide. However, the emergence of new strains in different countries and climates made SARS-CoV-2 an elusive target for prevention. The unpredictable range of symptoms in patients remains a cause of confusion and perplexity for clinicians.
Emerging data suggest that all patients presenting to a hospital with respiratory symptoms should be tested for COVID-19 with a high index of suspicion. Surgical societies have recommended testing all asymptomatic patients undergoing surgery with the fear of positive cases exposing all healthcare workers involved in their care. When hospitals were overwhelmed with COVID-19 cases, creating shortages of oxygen and hospital beds, elective cases were deferred, and all healthcare resources were diverted towards COVID-19 patients. In this context, patients with problems other than COVID-19 were subjected to long wait times, and some succumbed to their diseases due to a lack of prompt medical care. Those lucky enough to have found hospital beds were tested for COVID-19, and many were found to be infected. This prompted clinicians to search for other symptoms related to the virus. The coming months proved that SARS-CoV-2 could cause strokes, myocardial infarcts, mesenteric infarcts, acute limb ischemia, and a wide array of other symptomatology. This review aimed to establish whether COVID-19 is associated with pancreatitis.
A rapid review was performed to identify relevant cases.
The search engines used for the review were PubMed and Google Scholar, without any language restriction. The keywords used were “pancreatitis,” “necrotizing,” and “COVID-19.” Cases reported after January 2020 were included. A detailed review of the bibliography of the included cases was done.
The search results were evaluated by abstracts and titles. The full texts of the relevant studies were evaluated. All case reports or case series presenting patients with a clinical, radiological, or biochemical diagnosis of COVID-19 along with a clinical, biochemical, or radiological diagnosis of acute pancreatitis were included. No other predisposing factors of pancreatitis such as gallstones or endoscopic retrograde cholangiopancreatography were present.
Asad Ali Kerawala, Bhagwan Das, and Rabika Fatima performed the data retrieval. The country of the study, date of publication, age and sex of the patient, comorbidities, clinical course, any complications, treatment, and eventual outcome were recorded for all cases.
Tables 12–7 and 28–41 present the search results.
Table 1 . Reports of Patients with COVID-19 and Necrotizing Pancreatitis.
|Author||Date of publication||Country||Sex||Age (yr)||Comorbidity||Mode of COVID-19 diagnosis||Mode of pancreatitis diagnosis||Treatment||Outcome|
|Kumaran et al2||Sep 2020||UK||Female||67||HTN, SMA stenosis-1 year previously||RT-PCR||Abdominal CT||Conservative management including antibiotics||Alive|
|Mohammadi Arbati and Molseghi3||13 Apr 2021||Iran||Male||28||None||RT-PCR||Abdominal CT||Conservative management including antibiotics||Alive|
|Maalouf et al4||28 Jan 2021||Lebanon||Male||62||HTN, DM, ESRD, renal transplant||RT-PCR||Abdominal CT||Conservative management including antibiotics||Alive|
|Alloway et al5||6 Jun 2020||USA||Female||7||None||RT-PCR||Abdominal CT||Conservative management including antibiotics||Alive|
|Madhurantakam et al6||18 Dec 2020||India||Female||48||HTN, DM, ESRD on dialysis||RT-PCR||Abdominal CT||Invasive ventilation plus steroids, antibiotics||N/A|
|Liaquat et al7||Jul 2020||USA||Male||53||None||RT-PCR||Abdominal CT||Antibiotics, percutaneous drainage of necrotic collection, Steroids||Alive|
UK, United Kingdom; USA, United States of America; HTN, hypertension; SMA, superior mesenteric artery; DM, diabetes mellitus; ESRD, end-stage renal disease; RT-PCR, reverse transcriptase-polymerase chain reaction; CT, computed tomography; N/A, not available..
Table 2 . Patients with COVID-19 Presenting with Acute Pancreatitis (Non-Necrotizing).
|Author||Date of publication||Country||Sex||Age (yr)||Comorbidity||Mode of COVID-19 diagnosis||Mode of pancreatitis diagnosis||Treatment||Outcome|
|Meireles et al8||May 2020||Portugal||Female||36||HTN, ESRD||RT-PCR||Biochemical markers||Conservative management||Alive|
|Aloysius et al9||20 Jul 2020||USA||Female||36||Obesity||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Alive|
|Anand et al10||Jun 2020||UK||Female||59||Thrombophilia, history of cholecystectomy||RT-PCR||Abdominal CT||Conservative management||Alive|
|Hadi et al11||20 Jun 2020||Denmark||Female||47||None||RT-PCR||Biochemical markers and ultrasound||Invasive ventilation||N/A|
|Denmark||Female||68||HTN, hyperthyroidism||RT-PCR||Biochemical markers||Invasive ventilation||N/A|
|Gadiparthi et al12||23 Jun 2020||USA||Male||40||None||RT-PCR||Abdominal CT||Intensive care admission and conservative management||Alive|
|Suchman et al13||2 Jan 2021||USA||N/A||N/A||None||RT-PCR||Biochemical markers, clinical||Conservative management||Alive|
|Female||N/A||None||RT-PCR||Biochemical markers, clinical||Conservative management||Alive|
|Stevens et al14||Nov 2020||USA||Female||10||Obesity, asthma||RT-PCR||Abdominal CT||Intensive care admission and IV Immunoglobulins||Alive|
|Shinohara et al15||Nov 2020||Japan||Male||58||HTN||RT-PCR||Abdominal CT||Conservative management (antibiotics and steroids), ECMO||Alive|
|Kataria et al16||Jul 2020||Pakistan||Female||49||None||RT-PCR||Biochemical markers||Conservative management with antibiotics||Alive|
|Meyers et al17||Nov 2020||USA||Male||67||HTN, alcoholism||RT-PCR||Biochemical markers||Conservative management||Alive|
|Cheung et al18||Aug 2020||USA||Male||38||None||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Alive|
|Kandasamy et al19||Nov 2020||India||Female||45||None||RT-PCR||Abdominal CT||Conservative management||Alive|
|Jespersen Nizamic et al20||Dec 2021||USA||Female||49||CKD, renal transplant—on immunosuppressants||RT-PCR||Abdominal CT||Conservative management including tacrolimus||Alive|
|Narang et al21||Mar 2021||USA||Female||20||Pregnant, obesity, history of cholecystectomy||RT-PCR||MRCP||Steroids, preterm induction of labor||Alive|
|Gonzalo-Voltas et al22||Aug 2020||Spain||Female||76||Smoker, hypercholesterolemia||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Alive|
|Lakshmanan and Malik23||Aug 2020||USA||Male||68||ESRD, HTN, DM||RT-PCR||Abdominal CT||Conservative management||Alive|
|Simou et al24||Oct 2020||Morocco||N/A||67||DM, obesity, alcoholism, history of cholecystectomy||RT-PCR||Abdominal CT||Invasive ventilation||Expired|
|Wang et al25||Aug 2020||China||Male||42||None||RT-PCR||Biochemical markers and abdominal CT||Invasive ventilation||Expired|
|China||Male||35||None||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Alive|
|Brikman et al26||Jul 2020||Israel||Male||61||None||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Alive|
|Tollard et al27||Mar 2021||France||Female||32||Obesity, DM, DKA||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Expired|
|Acherjya et al28||Oct 2020||Bangladesh||Female||57||HTN, DM, breast cancer, and laryngeal cancer—receiving radiation and chemotherapy||RT-PCR||Abdominal CT||Conservative management||Alive|
|Karimzadeh et al29||Jun 2020||Iran||Female||65||HTN, Asthma||RT-PCR||Clinical and biochemical diagnosis||Conservative management||Alive|
|Mazrouei et al30||Jun 2020||UAE||Male||24||None||RT-PCR||Abdominal CT||Conservative management||Alive|
|Samies et al31||Feb 2021||USA||Male||15||None||RT-PCR||Biochemical markers||Conservative management||Alive|
|USA||Male||11||None||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Alive|
|USA||Female||16||History of pancreatitis||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Alive|
|Alwaeli et al32||Nov 2020||USA||Male||30||None||RT-PCR||Biochemical markers and abdominal CT||Conservative management including TPN||Alive|
|Purayil et al33||Aug 2020||Qatar||Male||58||None||RT-PCR||Clinical and biochemical diagnosis||Conservative management||Alive|
|Rabice et al34||May 2020||USA||Female||36||Pregnant, obese, DM, pre-eclampsia||RT-PCR||Clinical and biochemical diagnosis||Conservative management||Alive|
|Patnaik et al35||Sep 2020||India||Male||29||None||RT-PCR||Biochemical markers and abdominal CT||Conservative management including antibiotics||Alive|
|Pinte and Baicus36||Jun 2020||Romania||Male||47||None||RT-PCR||Abdominal CT||Conservative management||Alive|
|Alves et al37||Sep 2020||Brazil||Female||56||HTN||RT-PCR||MRCP||Intensive care management||Alive|
|Ibrahim et al38||Oct 2020||Qatar||Male||36||None||RT-PCR||Abdominal CT||Intensive care management plus hemodialysis||N/A|
|Miao et al39||Jul 2020||France||Female||26||None||RT-PCR||Abdominal CT||Conservative management||Alive|
|Bokhari and Mahmood40||Sep 2020||Pakistan||Male||32||None||RT-PCR||Biochemical markers and abdominal CT||Conservative management||Alive|
|Hassani et al41||2020||Iran||Female||78||HTN, IHD||RT-PCR||Clinical and biochemical diagnosis||Invasive ventilation||Expired|
UAE, United Arab Emirates; HTN, hypertension; ESRD, end-stage renal disease; CKD, chronic kidney disease; DM, diabetes mellitus; IHD, ischemic heart disease; DKA; diabetic ketoacidosis; RT-PCR, reverse transcription polymerase chain reaction; CT, computed tomography; MRCP, magnetic resonance cholangiopancreatography; ECMO, extracorporeal membrane oxygenation; TPN, total parenteral nutrition; N/A, not available..
Out of the 176 and 479 search results from Google Scholar and PubMed, respectively, 104 were relevant. After a detailed read, 35 publications fulfilled the inclusion criteria. The bibliography of these publications revealed 5 more articles pertinent to our study. Hence, a total of 38 publications (34 case reports and 4 case series) were analyzed.
In total, 44 cases of acute pancreatitis (38 cases of acute edematous pancreatitis and 6 cases of necrotizing pancreatitis) in COVID-19 patients without any predisposing factors have been published since January 2020. Even though quite a few authors claimed to be the first to report the combination, after thorough research we came to the conclusion that the first case reported was in May 2020 from Portugal by Meireles et al8 Journals around the world have considered all COVID-19 related studies for fast track publication—and rightly so, as our understanding evolved from viewing SARS-CoV-2 as a respiratory virus to recognizing it as a pathogen capable of causing multiorgan disease. For this reason, there was an overlap of cases published in mid-2020.
In the acute edematous cohort, 17 (44.7%) were males, 20 (52.6%) were females, and sex was not reported for 2 (5.3%) patients. The necrotizing group showed an even sex distribution, with three (50.0%) patients each. The median age of presentation was 45 years. The median ages of male and female patients were 38 and 47 years, respectively. The median age of patients with necrotizing pancreatitis was 50.5 years. The youngest case presented was necrotizing pancreatitis in a 7-year-old girl from the USA by Alloway et al5. Samies et al31 published a case series of three pediatric patients from the USA. The oldest patient reported was 78 years old from Iran.
The United States of America has been the country with the highest number of COVID-19 cases and deaths. The most cases reported were therefore from the USA itself (
Reverse-transcription polymerase chain reaction (RT-PCR) from a nasopharyngeal swab was used to confirm the diagnosis of COVID-19 in all patients. The diagnosis of acute pancreatitis was more varied. Computed tomography (CT) of the abdomen was the most frequently used modality for diagnosis, as it was performed in all (
Twenty-two patients had no comorbidities and no significant past medical history. Hypertension was the most common comorbidity, present in 12 patients (27.3%), followed by diabetes mellitus (
All six patients with necrotizing pancreatitis were treated with antibiotics and intensive care. Only one patient required invasive ventilation and one required percutaneous drainage of an infected collection.
In the acute edematous pancreatitis group, conservative management with bowel rest, intravenous fluids, analgesics, and anti-emetics in the ward was the most frequently used treatment modality (
Fortunately, death was reported in only four (9.1%) patients. Historically, pancreatitis itself is a deadly disease with an unpredictable course, and in combination with the deleterious effects of COVID-19 on the immune system, the expectation would be to have a high mortality rate. The unexpectedly low mortality rate could be due to the incomplete information available at the time of publication. These cases were all reported rapidly, with a short follow-up. None of the patients in the necrotizing pancreatitis cohort succumbed to the disease, and both pregnant women gave birth to healthy babies and returned home healthy.
Since the beginning of the COVID-19 pandemic caused by a respiratory virus, SARS-CoV-2, the medical literature has reported several extra-respiratory manifestations caused by this virus, including acute pancreatitis.
Acute pancreatitis is among the most common health care emergencies encountered during routine clinical practice.42 Around 10%–20% of cases of acute pancreatitis have been reported to involve necrosis of the pancreatic gland itself and/or surrounding peripancreatic tissue, a condition known as acute necrotizing pancreatitis.43
Infectious agents as an etiology of acute pancreatitis are not novel, as several infectious agents have been reported to infect the pancreas.44 Several viruses have been described in the literature as etiologies of viral pancreatitis; the most common among them are mumps, cytomegalovirus, coxsackievirus, and hepatitis A-E virus.45 The exact pathological mechanism by which these viruses induce pancreatic injury is still unknown. Some proposed mechanisms by which viruses can cause viral pancreatitis are the replication of viruses within acinar cells leading to the leakage and activation of pancreatic enzymes, cellular damage by ampullary edema, and cholangiopathy.46
Studies done during the previous SARS-CoV pandemic, in the early 2000s, reported the presence of viral RNA and antigen within the pancreatic tissues.47 Likewise, SARS-CoV-2 RNA was also detected in the fluid sampled from a pancreatic pseudocyst of a patient with pancreatitis and COVID-19 infection.48 Because of the genomic similarity of SARS-CoV-2 and SARS-CoV and the expression of angiotensin-converting enzyme 2 (ACE2) receptors of SARS-CoV-2 in pancreatic tissues,49,50 the pancreas can be assumed to be a potential target of SARS-CoV-2.
Though the exact mechanism by which SARS-CoV-2 causes pancreatitis is still unclear, but the extant studies have reported it to be a multifactorial phenomenon. COVID-19-associated pancreatic injury is thought to involve direct cellular damage via local replication of the virus within pancreatic cells, as they express ACE2 receptors at an even higher level than lung cells.50 SARS-CoV-2 has a high binding affinity for ACE2 receptors, and after binding to these receptors, the virus utilizes a variety of host proteins including transmembrane protease serine 2 (TMPRSS2) for easy cellular entry.51,52 In addition to direct injury, lipotoxicity has also recently been reported in COVID-19 patients, resulting in leakage of lipase from pancreatic cells and causing cellular damage.53
Furthermore, cytokine storm secondary to a dysregulated inflammatory response also causes pancreatic injury, as described by Liu et al50 in patients with severe COVID-19 disease. Thus, direct cellular injury, lipotoxicity, and severe inflammatory response syndrome in combination drive the disease progression, leading to not only pancreatitis, but also acute respiratory distress syndrome, multiorgan failure, and in some cases mortality.54,55
From precise published data, it can be concluded that acute pancreatitis is less common than other gastrointestinal manifestations seen in COVID-19 patients. It was reported slightly more frequently in female patients and at a relatively younger age in male patients, with no age-related immunity, as it was reported in patients from 7 years to 78 years of age. Abdominal CT was the most common imaging modality used for the diagnosis of both necrotizing (in 100% of cases) and non-necrotizing pancreatitis (in 63% of cases). As in several other studies,56–59 we found that hypertension was the most common comorbid condition in this review, followed by diabetes mellitus, obesity, and end-stage renal disease.
COVID-19 infection was confirmed by RT-PCR in all patients, and after confirmation of diagnosis, almost all patients diagnosed with pancreatitis received conventional conservative therapy with bowel rest, intravenous fluids, analgesics, and anti-emetics. Intensive care was required by all patients with necrotizing pancreatitis and in less than one-third of patients with edematous pancreatitis. Out of two pregnant patients, preterm labor was induced in one and the second one was managed conservatively.
The exact outcome data of acute pancreatitis in COVID-19 patients are quite difficult to report from this review, as the current status and complete follow-up of many patients were missing in the reported literature. This constitutes the most substantial limitation of our study. Mortality was reported in only 9% of the published cases in this review. The reason for this low mortality rate could be that viral pancreatitis is usually of mild severity, with most patients recovering on their own. The long-term effects of COVID-19 on the pancreas, as part of so-called “long COVID,” remain obscure. Only time will tell if any of these patients will develop chronic pancreatitis or pancreatic insufficiency in the long term. Although there are insufficient data to consider pancreatitis in all patients with COVID-19, the significant mortality associated with pancreatitis makes it imperative for the clinician to keep pancreatitis in the differential list in COVID-19 patients with any gastrointestinal symptoms.
Our review concludes that acute pancreatitis should be kept in the differential list of all COVID-19 patients with gastrointestinal manifestations, especially in patients with acute abdomen. Likewise, COVID-19 RT-PCR testing should be done in all patients diagnosed with acute pancreatitis for the timely isolation and observation of other COVID-19-associated complications.
No potential conflict of interest relevant to this article was reported.
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