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Case report
peer-reviewed

A Case Report on Acute Pancreatitis in a Patient With Coronavirus Disease 2019 (COVID-19) Pneumonia



Abstract

With the ongoing coronavirus disease 2019 (COVID-19) pandemic, there has been an explosion of scientific literature on the clinical manifestations and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Gastrointestinal symptoms occur in 15-20% of COVID-19 patients; however, there have not been many case reports on acute pancreatitis in COVID-19 patients. The expression of ACE-2 ([angiotensin-converting enzyme 2] the host receptor for SARS-CoV-2) is very high in the pancreas, which might be a contributing factor, but the high expression is mainly localized to endocrine pancreas. This case report describes a case of a 25-year-old Indian female with COVID-19 with acute pancreatitis in the absence of any other known risk factors for pancreatitis.

Introduction

The identification of a novel coronavirus had led to a cluster of severe pneumonia cases in Wuhan, China, in December 2019. The disease was later designated as coronavirus disease 2019 (COVID-19) [1] by the World Health Organization on March 11, 2020 [2]. Since its inception, there have been more than 83.3 million cumulative cases and 1.8 million deaths worldwide as of January 5, 2021 [3]. The clinical spectrum of the disease ranges from asymptomatic infection [4] to critical life-threatening respiratory disease [5]. However, the organ involvement in COVID-19 is not limited to the respiratory system, and several other organ systems can be involved. Data analysis indicates the presence of six distinct clusters of symptoms of COVID-19 [6], including gastrointestinal symptoms of varying severity. There has been evidence of pancreatic injury in COVID-19 patients, but this is often overlooked and the real prevalence of this complication is unknown. This case report highlights the case of a patient with COVID-19 pneumonia who developed acute pancreatitis.

Case Presentation

A 25-year-old Indian female with no significant past history presented to our emergency department with complaints of fever, headache, sore throat, dry cough, and loss of taste sensation for nine days, and abdominal pain with vomiting for two days. Her COVID reverse transcription polymerase chain reaction (RT-PCR) test performed on the second day of her illness returned positive. Subsequent to her first positive RT-PCR, the patient was started on oral favipiravir, tablet ivermectin 12 mg once daily for three days, and other supportive therapy. The patient did not have shortness of breath at this time or a history of smoking or alcohol intake. On the eighth day of illness, the patient started experiencing severe, dull aching, epigastric pain radiating to the back, with vomiting. The investigations on her eighth day of illness revealed that her repeat COVID RT-PCR was positive, C-reactive protein was 18.62 mg/L, D-dimer was highly elevated (>5,000 ng/mL) and serum lipase was 2,052.61 U/L (>3 times upper limit of normal). She was then admitted to our hospital on the ninth day of illness as a case of COVID-19 with suspected acute pancreatitis. On physical examination, her vitals were normal and epigastric tenderness was appreciated. Her investigations before and after admission are shown in Table 1, indicating a pro-inflammatory and hyper-coagulable state of COVID-19.

Parameter Day 9 Day 11 Day 13 Day 14 Day 15 Day 16
COVID RT-PCR - - Negative Negative - -
TLC (cells/mm3) 9700 7010 6730 7400 5490 6400
Neutrophil (cells/mm3) 7700 5570 5320 5700 4350 4780
Lymphocyte (cells/mm3) 1300 940 1110 1200 870 1000
NLR 5.7 5.92 4.79 4.9 5.0 4.78
Hemoglobin (g/dL) 11.6 10.0 10.0 10.1 11.0 11.2
Platelet count (x103/mm3) 190 184 183 236 267 256
Eosinophil (cells/mm3) 100 80 0 - 0 90
CRP (mg/L) 52.6 81.9 62.1 34.9 27.6 37.4
D-dimer (ng/mL) 3627 11,100 1850 3600 442 606
NT-proBNP (pg/mL) - 3990 2320 5010 - -
Troponin I - 0.021 <0.010 <0.010 - -
Procalcitonin 0.030 0.24 0.13 0.096 - -
Serum amylase 1814 -     - -
Serum lipase 11920 - 301 275.3 225 327
IL-6 514.6 -     - -
Urea 22.6 19.7 38 19.2 - -
Creatinine 0.8 0.7 0.5 0.6 - -
Calcium 9.2 8.7 9.0 - - -
Blood sugar 83.8 81.1 - - - -
ESR 55 - - - - -
HbA1c 5.83 - - - - -
SGOT 24 23.4 - - - -
SGPT 25.4 18.7 - - - -
ALP 121.1 100.0 - - - -
Serum bilirubin 0.6 0.8 - - - -
Ferritin 44.9 - - - - -
Triglycerides 97.4 - - - - -
Prothrombin time - 16.2 - - - -
VDRL Negative
Malaria antigen Negative
HIV Negative
HBsAg Negative
Anti-HCV antibody Negative
Blood culture Negative
TSH 2.54

A contrast-enhanced CT of the whole abdomen showed a bulky pancreas with poor enhancement, no parenchymal necrosis or calcification (Figures 1, 2), with soft tissue stranding and inflammatory changes in peripancreatic and mesenteric fat; renal and lateroconal fascial thickening (Figure 3); and mild free fluid in peritoneal cavity and pelvis (Figure 4); which further confirmed our diagnosis of acute interstitial pancreatitis (fulfilling all three criteria of acute pancreatitis as per the revised Atlanta classification) with mild ascites (modified CT Severity Index - 6).

The high-resolution CT of the chest showed patchy ground-glass opacities in the left lung, CO-RADS 6 ([COVID-19 Reporting and Data System] RT-PCR positive), CT severity score of 3/25 (Figures 5A, 5B), and bilateral pleural effusion (left > right) (Figure 6).

A screening 2D-ECHO (echocardiography) indicated no regional wall motion abnormality and a left ventricular ejection fraction of 60%. She was managed conservatively and kept nil per os with nasogastric suction, judicious intravenous (IV) fluids, IV antibiotics (piperacillin-tazobactam and metronidazole), IV methylprednisolone 40 mg once daily, subcutaneous enoxaparin 60 mg twice daily, and other supportive measures. On her third day of admission (day 11 of illness), she required transfer to the intensive care unit for respiratory distress and increased oxygen requirement. She was also switched to IV imipenem and started on IV remdesivir. The possibility of microthrombi formation in the pulmonary circulation (highly elevated D-dimer: 11,100 ng/mL), leading to pulmonary hypertension and myocardial stress (elevation of NT-proBNP [N-terminal-pro-B-type natriuretic peptide]: 3,990 pg/mL) was kept, and the patient was started on IV furosemide 20 mg once daily. The patient started showing significant improvement in abdominal pain and shortness of breath, and her oxygen requirement started decreasing. Her repeat COVID RT-PCR was negative on days 13 and 14 of illness (days 5 and 6 of admission), and she was able to tolerate oral liquid diet. She was off oxygen support and able to tolerate full oral diet by day 7 of admission and was discharged on day 9 of admission. A timeline of events (symptoms, treatment initiated) prior to admission is depicted (Figure 7). A graphical representation of her CRP (C-reactive protein), D-dimer, and NT-proBNP during the course of illness (after admission) is depicted (Figure 8).

Discussion

Patients with COVID-19 frequently present with gastrointestinal symptoms. In a report of over 3,70,000 cases of COVID-19, 19% had diarrhea, 12% had nausea/vomiting, and 7.6% had abdominal pain [7]. A meta-analysis and systematic review of 60 studies of gastrointestinal manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection estimated the pooled prevalence of gastrointestinal symptoms at 17.6% overall (13% for diarrhea, 10% for nausea/vomiting, and 9% for abdominal pain) [8], particularly higher in the severely ill. However, to date, there have not been many case reports of acute pancreatitis in COVID-19.

The diagnosis of acute pancreatitis requires two out of the following three features (as per the revised Atlanta classification) [9]: (1) abdominal pain consistent with acute pancreatitis, (2) serum lipase or amylase activity at least three times greater than the upper limit of normal, and (3) characteristic findings of acute pancreatitis on contrast-enhanced CT or MRI or USG. The common causes of pancreatitis, which were ruled out in this case, included biliary tract disease (e.g. gallstones), alcohol, hypertriglyceridemia, hypercalcemia, trauma, history of surgical procedures/post-ERCP (endoscopic retrograde cholangiopancreatography), developmental anomalies, and tumors. Drug-induced pancreatitis has not been reported with either ivermectin or favipiravir. Infections with viruses, helminths, and protozoa are known to cause pancreatitis, and viral infections such as those from hepatitis viruses, Coxsackie viruses, Echoviruses, mumps virus, cytomegalovirus, Epstein-Barr virus, Varicella Zoster virus, and influenza virus (H1N1) are the most common infectious cause (65% cases) of acute pancreatitis [10].

Anand et al. [11] reported the development of acute pancreatitis in a patient 10 days after the first positive PCR report. The patient was readmitted after discharge with fever, abdominal pain, and constipation, and CT obtained on day 3 of readmission indicated acute pancreatitis [11]. They raised the possibility of an association between this novel coronavirus and acute pancreatitis [11]. The temporal presentation of acute pancreatitis in their case matches that of our case; however, a serum amylase level test was not done in their patient on admission.

Another case report of acalculous acute pancreatitis in a COVID-19 patient was reported by Meireles et al. [12], where the patient developed nausea, vomiting, and pain abdomen on the 11th day of the disease. Her investigations revealed a 10-fold rise in her amylase and lipase levels, and imaging did not reveal any evidence of calculi or ischemia [12]. They suggested that pancreatic involvement likely arose from an immune inflammatory response to the virus (rather than direct viral invasion) given the temporal association between the development of pancreatitis and the clinical picture [12].

Hadi et al. [13] described the cases of three family members admitted with COVID-19, two of whom developed severe acute pancreatitis. The authors did not find a reason as to why only two of the five cases in the family developed acute pancreatitis. Both of them had severe pancreatitis with acute respiratory distress syndrome (ARDS) and multi-organ failure, and whether severe pancreatitis caused the ARDS and multi-organ failure or COVID-19 caused it could not be ascertained [13]. Kumaran et al. [14] reported the case of a 67-year-old hypertensive female who presented with one-day history of epigastric pain, nausea, and vomiting and was found to have acute necrotising pancreatitis after due investigations. In that case also, common causes of acute pancreatitis were ruled out, but the patient did have a positive history of superior mesenteric artery stenosis one year ago, for which she underwent surgery and was on apixaban. She later developed tachypnea and hypoxia and was found to be COVID-19 positive [14]. It highlights the fact that patients with COVID-19 may even present with pancreatitis, and the worsening of respiratory system after the development of acute pancreatitis in their case matches that of our case.

The presence of viral RNA in fecal specimens and gastrointestinal epithelium despite negative respiratory tests has led to the suggestion of a possible feco-oral transmission route for SARS-CoV-2 [15]. The expression of ACE-2 ([angiotensin-converting enzyme 2] the host receptor for SARS-CoV-2 entry) is very high in the pancreas and gastrointestinal epithelium [16].

The endocrine part of the pancreas strongly expresses ACE-2, whereas exocrine tissues are only weakly positive; consequently, there are very few reports of pancreatitis in patients with SARS [17] or COVID-19. Wang et al. [18] reported that 17% patients of COVID-19 had evidence of pancreatic injury (defined as elevation of pancreatic enzymes), and two-thirds of those patients had abnormal blood glucose levels [18]. They attributed this injury possibly due to either direct cytopathic effect of SARS-CoV-2 or mediated by the immune response directed against SARS-CoV-2 [18]. In another study by Liu et al. [19] of 121 patients with COVID-19, only one out of 54 mild cases had pancreatic enzyme elevation, but in severe cases, 12 out of 64 cases (17.9%) had enzyme elevation, but no case had necrotising pancreatitis [19]. Clinicians should have a high index of suspicion for pancreatic injury in patients with COVID-19 (especially in those with pancreatic enzyme elevation), as it can be a life-threatening complication.

There are some lessons to be learned here from the 2002-2004 SARS epidemic. The pancreatic involvement in SARS was not only limited to pancreatic enzyme elevation. The development of acute diabetes in 20 out of 39 patients of SARS (who were initially non-diabetic) was noted by Yang et al. [17]. Of those 20 patients, 18 returned to normoglycemia in the three-year follow-up of the study [17]. This indicated that SARS-CoV-1 caused damage to pancreatic islets and caused acute diabetes. Considering the genetic similarities between SARS-CoV-1 and 2, the potential for permanent pancreatic damage, chronic pancreatitis, and acute or chronic diabetes due to SARS-CoV-2 cannot be overlooked.

Hanley et al. [20] reported the histopathological post-mortem findings in 10 patients over the age of 18 years who died due to COVID-19. The most consistent findings were diffuse alveolar damage, thrombosis, and immune cell depletion primarily affecting the lungs, hearts, and kidneys [20]. But the unexpected finding was pancreatitis in two patients, with the first having gross necrotising hemorrhagic pancreatitis and the second having only microscopic evidence of acute inflammation in the pancreas [20]. While it was not obvious what determines the spread of SARS-CoV-2 outside the respiratory tract (as the sites of highest ACE-2 expression did not correlate with severity of pathological involvement), it possibly depends on several other factors such as cellular receptor status, route of transmission, and host factors (genetic makeup, TMPRSS2 expression/polymorphism, etc.) [20].

Conclusions

Respiratory, cardiac, renal, and multi-organ failure, as well as thrombosis are the most common causes of mortality in patients with COVID-19. Acute pancreatitis can be a rare cause of mortality, especially in those with moderate-to-severe disease. Patients with COVID-19 may be screened for pancreatic injury, as it may have an effect on prognosis. Larger studies are required to confirm the cause and pathogenesis of acute pancreatitis in COVID-19.


References

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  2. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. (2020). Accessed: November 22, 2020: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-....
  3. COVID-19 Weekly Epidemiological Update - 5 January. (2021). Accessed: January 11, 2021: https://www.who.int/publications/m/item/weekly-epidemiological-update---5-january-2021.
  4. Oran DP, Topol EJ: Prevalence of asymptomatic SARS-CoV-2 infection: a narrative review. Ann Intern Med. 2020, 173:362-7. 10.7326/M20-3012
  5. Wu Z, McGoogan JM: Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020, 323:1239-42. 10.1001/jama.2020.2648
  6. Wise J: Covid-19: study reveals six clusters of symptoms that could be used as a clinical prediction tool. BMJ. 2020, 370:2911. 10.1136/bmj.m2911
  7. Stokes EK, Zambrano LD, Anderson KN, et al.: Coronavirus disease 2019 case surveillance - United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020, 69:759-65. 10.15585/mmwr.mm6924e2
  8. Cheung KS, Hung IFN, Chan PPY, et al.: Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a Hong Kong cohort: systematic review and meta-analysis. Gastroenterology. 2020, 159:81-95. 10.1053/j.gastro.2020.03.065
  9. Banks PA, Bollen TL, Dervenis C, et al.: Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013, 62:102-11. 10.1136/gutjnl-2012-302779
  10. Imam Z, Simons-Linares CR, Chahal P: Infectious causes of acute pancreatitis: a systematic review. Pancreatology. 2020, 20:1312-2. 10.1016/j.pan.2020.08.018
  11. Anand ER, Major C, Pickering O, Nelson M: Acute pancreatitis in a COVID-19 patient. Br J Surg. 2020, 107:e182. 10.1002/bjs.11657
  12. Meireles PA, Bessa F, Gaspar P, Parreira I, Silva VD, Mota C, Alvoeiro L: Acalculous acute pancreatitis in a COVID-19 patient. Eur J Case Rep Intern Med. 2020, 7:001710. 10.12890/2020_001710
  13. Hadi A, Werge M, Kristiansen KT, Pedersen UG, Karstensen JG, Novovic S, Gluud LL: Coronavirus disease-19 (COVID-19) associated with severe acute pancreatitis: case report on three family members. Pancreatology. 2020, 20:665-7. 10.1016/j.pan.2020.04.021
  14. Kumaran NK, Karmakar BK, Taylor OM: Coronavirus disease-19 (COVID-19) associated with acute necrotising pancreatitis (ANP). BMJ Case Rep. 2020, 13:237903. 10.1136/bcr-2020-237903
  15. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H: Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020, 158:1831-3. 10.1053/j.gastro.2020.02.055
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  17. Yang JK, Lin SS, Ji XJ, Guo LM: Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010, 47:193-9. 10.1007/s00592-009-0109-4
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  19. Liu F, Long X, Zhang B, Zhang W, Chen X, Zhang Z: ACE2 expression in pancreas may cause pancreatic damage after SARS-CoV-2 infection. Clin Gastroenterol Hepatol. 2020, 18:2128-30. 10.1016/j.cgh.2020.04.040
  20. Hanley B, Naresh KN, Roufosse C, et al.: Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe. 2020, 1:245-53. 10.1016/S2666-5247(20)30115-4

Case report
peer-reviewed

A Case Report on Acute Pancreatitis in a Patient With Coronavirus Disease 2019 (COVID-19) Pneumonia


Author Information

Aviral Gupta Corresponding Author

Department of General Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, IND

Dharam P. Bansal

Department of General Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, IND

Puneet Rijhwani

Department of General Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, IND

Vipasha Singh

Department of Radiology, Mahatma Gandhi Medical College and Hospital, Jaipur, IND


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Mahatma Gandhi Medical College and Hospital issued approval MGMCH/IEC/JPR/2021/271. Subject:- “-A case report on acute pancreatitis in a patient with coronavirus disease 2019 (COVID-19) pneumonia.” submitted for ethics committee approval.
Dear Sir/Madam,
Your letter for permission to conduct the above mentioned study was reviewed and discussed in the meeting of the Institutional Ethics Committee held on 6th March 2021.

The following members of the ethics committee were present during the meeting:
Dr. R.P. Kothari, Retd. Professor , General Medicine - CHAIRMAN *
Dr. Rajendra kumar Sureka , PHOD, Neurology, MGMC&H, Jaipur- MEMBER SECRETARY
Dr. Puneet Rijhwani, PHOD, General Medicine, MGMC&H, Jaipur – Clinician
Dr. R.C. Gupta, Professor-Anaesthesia & Additional Medical Superintendent, MGMC&H, Jaipur – Clinician
Dr. B.N. Sharma, PHOD, Community Medicine, MGMC&H, Jaipur – Social Scientist
Dr. Munish Kumar Kakkar, PHOD, Paediatrics, MGMC&H, Jaipur – Clinician
Dr. Anusha Vohara ,PHOD ,Pharmacology- Basic Medical Scientist
Dr. Monica Jain Member-EC, Associate Professor, Department of Pharmacology, SMSMC, Jaipur (Basic Medical Scientist)
Mr. Siddhant Jain , Advocate-Legal Advisor - Legal Expert
Dr. Manju Bhaskar , Associate Professor, Psychiatry, MGMC&H, Jaipur. - Clinician
Dr. Amitabh Dube, Member Secretary-EC, Senior Professor, Department of Physiology, SMSMC, Jaipur. (Basic Scientist)
Dr.(Mrs.)Lata Joshi, Lay Person from the Community-Lay Person.
The Research Project in prescribed format A,B and C submitted by you were reviewed by the committee.
The Committee approves the above mentioned study. The Committee fee of the IEC is exempted. This is certified that investigator or his/her representative was not present during the decision making procedure /discussion. The Ethics committee expects to be informed about:
• The progress of the study time as well as about the completion of the study. • Any changes in the protocol and patient information/informed consent. • You will strictly follow the guidelines of schedule Y, ICMR, ICH-GCP,
instructions of DCGI New Delhi, and also the SOP of this institution. • In case of any deviation, default or any unlawful activity, your study will be
discontinued under intimation to the DCGI and ICMR New Delhi. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.



Case report
peer-reviewed

A Case Report on Acute Pancreatitis in a Patient With Coronavirus Disease 2019 (COVID-19) Pneumonia


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