{"paper_id":"b4a5ef7c-47a2-401c-820f-e6db809f4b3f","body_text":"Already in its third wave of new cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued for one year keeping the world under a pandemic with more than 2.8 million deaths. ( 1 )  The virus was initially detected in December 2019 in Wuhan, China, with atypical findings of viral pneumonia. On March 11, 2020, the virus had spread across the globe, and a pandemic for coronavirus 2019 disease (COVID-19) was determined by the World Health Organization (WHO). ( 2 )\nAs the number of cases increased, extrapulmonary symptoms were found, such as ageusia, anosmia, diarrhea, myocarditis, and urticaria, among others. ( 3 )  This was due to the ability of the virus to infect the host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, which is present in various tissues, such as the respiratory tract, cardiovascular system, kidneys, and intestines. ( 4 )  Among the gastrointestinal manifestations, an incidence of 3% to 79% of symptoms was detected, ranging from vomiting, anorexia, diarrhea, and nausea to gastrointestinal bleeding. ( 5 )\nMiao et al., reported the first case of acute pancreatitis in a patient with COVID-19 without respiratory symptoms. ( 6 )  Along the same line, other studies were published regarding pancreatic involvement by SARS-CoV-2, suggesting that the virus can cause pancreatic injury. ( 7 )  Supporting these findings, Liu et al., identified that ACE2 receptor is expressed in the pancreas in healthy people, and is even slightly more significant in pancreatic tissue than in the lungs, proposing that SARS-CoV-2 may cause pancreatic injury by binding to pancreatic ACE2. ( 8 )\nFew pathological studies in patients with COVID-19 have been performed with emphasis on the pancreas to support these hypotheses, but it was possible to find autopsies in the literature describing degeneration of pancreatic cells, ( 9 )  interstitial fibrosis, and lipomatosis separating the acinar cells ( 10 )  in these patients, besides detecting SARS-CoV-2 RNA in pancreatic cells. ( 11 )\nAcute pancreatitis is a potentially severe disease, with the main causes being cholelithiasis (40% to 70%), and alcoholism (25% to 35%). Other rare causes (10%), such as medications, trauma, endoscopic retrograde cholangiopancreatography (ERCP), hyperkalemia, hypertriglyceridemia (>1,000mg/dL), infection, genetics, and autoimmune diseases. ( 12 )  Among the infectious agents are viruses (hepatotropic, coxsackievirus, cytomegalovirus (CMV), human immunodeficiency virus (HIV), herpes simplex virus, paramyxovirus, and varicella-zoster virus), bacteria (mycoplasma,  Legionella, Salmonella , and leptospira), fungi ( Aspergillus ), and parasites (toxoplasma,  Cryptosporidium,  and  Ascaris ). ( 13 )\nIn the current context, in which several articles described acute pancreatitis in patients who tested positive for COVID-19 infection, it is suggested the virus may be another infectious cause of pancreatic injury, as well as several other agents described here.\n\nTo investigate the capacity of SARS-CoV-2 of causing acute pancreatitis and the peculiarities in diagnosis and care of these cases.\n\nThe database chosen was PubMed ® . On February 16, 2020, articles with the words “COVID-19” and “acute pancreatitis” were selected. From this search, 105 articles were found; one article was added manually. Inclusion criteria were studies that associated acute pancreatitis with COVID-19, as well as those about hyperlipasemia or hyperamylasemia and COVID-19. Exclusion criteria were articles about acute pancreatitis from another well-defined cause; in letter or comment form; with patients with a negative result for COVID-19; about the treatment of pancreatitis; about multisystem inflammatory syndrome of the child; and that did not deal with acute pancreatitis.  Figure 1  shows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram, based on the reading of titles and abstracts; 30 articles were excluded, leaving 74. Of these, 12 were excluded because they dealt with the mechanism of action of the virus, acute pancreatitis with negative COVID-19 results; they either did not mention the disease or pancreatic alterations, or had a defined cause for acute pancreatitis. Sixty-two articles were then included. The initial analysis was done by the main author and later reviewed by the supervisor of this work. Information such as patients’ age, comorbidities, and personal history, chief complaint, gastrointestinal symptoms, pneumonia, or severe acute respiratory syndrome (SARS), type of COVID-19 diagnostic test, medications, laboratory and imaging tests, and diagnostic criteria for pancreatitis, whenever cited, were used for analysis in this study. Regarding the diagnostic criteria, the Revised Atlanta Classification of acute pancreatitis, of 2012, was considered standard. Among the radiological findings, localized or diffuse enlargement of the pancreas, blurring of peripancreatic fat, presence of periglandular collections, pancreatic necrosis, and pancreatic pseudocyst were considered late presentations. Regarding the increase in pancreatic enzymes, hyperamylasemia shows high sensitivity and low specificity, whereas hyperlipasemia shows high sensitivity and specificity for the diagnosis of acute pancreatitis.\nFigure 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram\n\nThe research findings were divided into three tables, one containing literature reviews, prospective and retrospective studies ( Table 1 ), another with the case reports ( Table 2 ), and the last with the frequencies of the case report findings ( Table 3 ).\nTable 1 Data from prospective, retrospective studies, and literature reviews Studies Type of article Patients (n) Age (median) Amylase/lipase (U/L) Diagnosis of pancreatitis Relation between COVID-19 and acute pancreatitis? Zippi et al. (7) Review 14 - - - Yes Suchman et al. (14) Cohort 13 12 Amylase and lipase >3x INSPPIRE Yes Hegyi et al. (15) Meta-analysis 12 - - - Yes Akarsu et al. (16) Prospective study 316 54 Amylase and lipase >3x Modified Atlanta Classification Yes Gupta (17) Meta-analysis 4 53 Amylase and lipase >3x - Yes Juhász et al. (18) Systematic review 8 - - Atlanta Classification No McNabb-Baltar et al. (19) Cohort 71 64.9 Lipase >60 Atlanta Classification No Miró et al. (20) Case-control 54 - Amylase >3x Atlanta Classification No Lax et al. (21) Prospective study (autopsy) 11 80.5 - - Yes Rasch et al. (22) Cohort 38 68.5 Mean lipase of 422U/L Modified Atlanta Classification No Inamdar et al. (23) Cohort 32 53.44±16.60 Amylase and lipase >3x Atlanta Classification Yes Dirweesh et al. (24) Cohort 14 55.2±14.8 - Atlanta Classification Yes Hanley et al. (25) Cohort 8 - - Autopsy Yes Szatmary et al. (26) Cohort 5 42 Median amylasemia of 149U/L Atlanta Classification Yes Gubatan et al. (27) Cohort 8 55.3±18.7 - - No Akkus et al. (28) Cohort 20 55.5±18.9 Mean lipase of 91U/L Atlanta Classification No Samanta et al. (29) Systematic review 5 - - - No Shiralkar et al. (30) Cohort 10 45.1±19.6 - Abdominal CT and MRI Yes Pandanaboyana et al. (31) Cohort 149 59.9±17.2 Hyperamylasemia Modified Atlanta Classification Yes Goyal et al. (32) Systematic review 7 - Hyperlipasemia - No Rathi et al. (33) Cohort 83 - Median lipase of 391U/L - No McGuinness et al. (34) Cohort 650 57 Lipase >3x Atlanta Classification No Wang et al. (35) Cohort 52 55±15 Median amylase of 115±25U/L Median lipase of 71±34U/L >90U/L amylase and >70U/L lipase with pancreatic injury Yes INSPIRRE: International Study Group of Pediatric Pancreatitis: In Search for a CuRE; CT: computed tomography; MRI: magnetic resonance imaging.\nINSPIRRE: International Study Group of Pediatric Pancreatitis: In Search for a CuRE; CT: computed tomography; MRI: magnetic resonance imaging.\nTable 2 Key data from the case reports  Article data   Miao et al. (6)  Aloysius et al. (36)  Anand et al. (37)  Hadi et al. (38)  Hadi et al. (38)  Meireles et al. (39)  Age   26   36   59   47   68   36   Sex   Female   Female   Female   Female   Female   Female   Past history   -   Obesity and anxiety disorder   Thrombophilia and prior cholecystectomy   -   HTN, hypothyroidism, and osteoporosis   Post-HELLP syndrome, CKD, and HTN   Initial symptoms   Vomiting, epigastric pain, and fever   Fever, dry cough, dyspnea, nausea, vomiting, and diarrhea   Fever, sore throat, and myalgia   Fever, headache, anorexia, sore throat, and dyspnea   Epigastric pain and fever   Dry cough, fever, and dyspnea   GIT symptoms   Yes   Yes   Yes   No   Yes   Yes   Abdominal pain   Epigastric   Band-like epigastric pain irradiating towards the back   -   -   Epigastric   Band-like epigastric pain   Pneumonia   Yes   Yes   Yes   Yes   Yes   Yes   SARS   No   Yes   No   Yes   Yes   Yes   Test to confirm COVID-19   RT-PCR   RT-PCR   RT-PCR   RT-PCR   RT-PCR   ?   Amylase, U/L   Not done   325   Not done   >1,500   934   718   Lipase, U/L   430   627   Not done   Not done   Not done   631   CRP, mg/dL   1.38   1.95   6.27   -   7.7   11.9   Imaging test suggestive of acute pancreatitis   Abdominal CT scan   No   Abdominal CT scan   Abdominal ultrasound   No   Abdominal CT scan   Triglycerides, mg/dL   Not done   136   Not done   Normal   Normal   120   Cholelithiasis or alcoholism   No   No   No   No   No   No   Diagnosis of pancreatitis   Imaging, clinical, and laboratory   Modified Atlanta Classification   Suggestive abdominal CT scan   Modified Glasgow Coma Score for Acute Pancreatitis (5 points)   Modified Glasgow Coma Score for Acute Pancreatitis (5 points)   Imaging, clinical, and laboratory   CUM   -   Alprazolam   -   -   Losartan, levothyroxine, alendronate, and cyanocobalamin (Vitamina B12)   Nifedipine and carvedilol   Medication on admission   -   -   -   -   -   -   Complications     NIV   -   OTI and mechanical ventilation, hemodialysis, and ECMO   OTI and mechanical ventilation, and hemodialysis   -   Outcome   Resolution   Resolution   Resolution   Not available   Not available   Resolution  \n \n Article data Shinohara et al. (40) Meyers et al. (41) Cheung et al. (42) Kandasamy et al. (43) Lakshmanan et al. (44)   \n \n  Age   58   67   38   45   68   Sex   Male   Male   Male   Female   Male   Personal antecedents   HTN   HTN and cholecystectomy   -   ?   DM, HTN, and CKD   Initial symptoms   Fever and dyspnea   Epigastric pain, fever, tachycardia, and tight abdomen   Fever, intense epigastric pain, nausea, and vomiting   Epigastric pain irradiating towards the back, nausea, and vomiting   Loss of appetite and nausea   GIT symptoms   Yes   Yes   Yes   Yes   Yes   Abdominal pain   -   Epigastric   Epigastric   Epigastric irradiating towards the back   Denies   Pneumonia   Yes   Yes   No   Yes   No   SARS   Yes   No   No   No   No  Article data Shinohara et al. (40) Meyers et al. (41) Cheung et al. (42) Kandasamy et al. (43) Lakshmanan et al. (44)  Test to confirm COVID-19   RT-PCR   RT-PCR   RT-PCR   RT-PCR   RT-PCR   Amylase, U/L   383   Not done   Not done   364   1,030   Lipase, U/L   Not done   5,295   1,219.2   293   2,035   CRP, mg/dL   11.51   Not done   Not done   Not done   15.8   Imaging test suggestive of acute pancreatitis   Abdominal CT scan   Abdominal CT scan   Abdominal CT scan and MRI   Abdominal CT scan   Abdominal CT scan   Triglycerides, mg/dL   Not done   Normal   Normal   Not done   Normal   Cholelithiasis or alcoholism   No   Mild alcoholism   No   No   No   Diagnosis of pancreatitis   Imaging, clinical, and laboratory   Abdominal CT   Abdominal CT   Abdominal CT   Imaging, clinical, and laboratory   CUM   -   -   -   -   -   Medication on admission   Piperacillin- tazobactam, azithromycin, favipiravir, nafamostat mesilate, and methylprednisolone   -   -   Empirical antibiotic   Empirical antibiotic   Complications   OTI and ECMO   Not available   -   NIV   -   Outcome   Resolution   Not available   Resolution   Resolution   Resolution  \n \n Article data Gonzalo-Voltas et al. (45) Brikman et al. (46) Narang et al. (47) Wang et al. (48) Wang et al. (48) \n \n  Age   76   61   20   42   35   Sex   Female   Male   Female   Male   Male   Past history   Hypercholesterolemia and GERD   -   Primigesta, 33- week gestation, obesity, and cholecystectomy   -   -   Initial symptoms   Epigastric pain and vomiting   Fever, dyspnea, and cough   Dry cough and myalgia   Nausea and epigastic pain   Abdominal pain, nausea, and vomiting   GIT symptoms   Yes   Yes   Yes   Yes   Yes   Abdominal pain   Band-like epigastric pain   Diffuse abdominal pain   Epigastric pain irradiating to the back   Epigastric pain irradiating to the back   Epigastric pain irradiating to the back   Pneumonia   No   Yes   Yes   Yes   Yes   SARS   No   Yes   Yes   Yes   No   Test to confirm COVID-19   RT-PCR   RT-PCR   RT-PCR   RT-PCR   RT-PCR   Amylase, U/L   3,568   142   1,168   132   Normal   Lipase, U/L   Not done   203   859   382   1,042   CPR, mg/dL   1.9   -   -   >20   >20   Imaging test suggestive of acute pancreatitis   Abdominal CT and ultrasound   Abdominal CT   Abdominal CT   -   Abdominal CT   Triglycerides, mg/dL   Not done   281.67   -   283.44   170.06   Cholelithiasis or alcoholism   No   No   No   No   No   Diagnosis of pancreatitis   Imaging, clinical, and laboratory   Modified Atlanta Classification   Presumptive   Ranson   Imaging, clinical, and laboratory   CUM   Omeprazole 20mg/day   -   -   -   -  \n \n Article data Gonzalo-Voltas et al. (45) Brikman et al. (46) Narang et al. (47) Wang et al. (48) Wang et al. (48) \n \n  Medication on admission   Azithromycin, chloroquine, lopinavir, and ritonavir   Azithromycin, hydroxychloroquine, zinc, tocilizumabe, dexamethasone, enoxaparin, lopinavir- ritonavir, pantoprazole, ciprofloxacin, and clindamycin   -   -   -   Complications   -   NIV   NIV and premature rupture of membranes, and preterm birth   Cardiac arrest, OTI and mechanical ventilation, and hemodialysis   -   Outcome   Resolution   Resolution   Resolution   Death   Resolution  \n \n Article data Tollard et al. (49) Acherjya et al. (50) Karimzadeh et al. (51) Simou et al. (52) Mazrouei et al. (53) \n \n  Age   32   57   65   67   24   Sex   Female   Female   Female   ?   Male   Past history   Morbid obesity and diabetic ketoacidosis   HTN, type 2 DM, breast and larynx cancer, and prior cholecystectomy   HTN and asthma   Type 2 DM, obesity, and prior cholecystectomy   -   Initial symptoms   Dyspnea, polyuria, polydipsia, and abdominal pain   High fever, myalgia, anosmia, fatigue, and arthralgia   Epigastric pain, nausea, chills, and myalgia. On the 7 th  day, the patient presented with dyspnea   Fever, dyspnea, myalgia, and arthralgia   Epigastric pain, nausea, vomiting, and mild respiratory symptoms   GIT symptoms   Yes   Yes   Yes   No   Yes   Abdominal pain   Abdominal   Epigastric pain irradiating to the back   Epigastric   No   Epigastric   Pneumonia   Yes   Yes   Yes   Yes   No   SARS     No   No   No   No   Test to confirm COVID-19   RT-PCR   RT-PCR   RT-PCR   RT-PCR   RT-PCR   Amylase, U/L   Not done   Not done   192   -   391   Lipase, U/L   321   8,352   283   576   578   CRP, mg/dL   -   25.2   -   4.13   -   Imaging test suggestive of acute pancreatitis   Abdominal CT scan   Abdominal CT scan   Abdominal CT scan   Abdominal CT scan   Abdominal CT scan   Triglycerides, mg/dL   Normal   276   80   212.58   Not done   Cholelithiasis or alcoholism   No   No   No   No   No   Diagnosis of pancreatitis   Imaging, clinical, and laboratory   Atlanta Classification   Clinical   Balthazar Classification of Abdominal CT   Atlanta Classification   CUM   -   Radiation therapy, trastuzumab, losartan, metformin, and insulin   -   -   -   Medication on admission   -   Favipiravir and enoxaparin in prophylactic dose   Levofloxacin, ondansetron, oseltamivir, hydroxychloroquine, ribavirin, lopinavir, ritonavir, vancomycin, cefepime, and oxygen therapy   Oxygen therapy, hydroxychloroquine, azithromycin, methylprednisolone, vitamin C, zinc, and enoxaparin   -   Complications   Diabetic ketoacidosis, pulmonary thromboembolism, OTI and mechanical ventilation, and distributive shock   NIV   NIV   NIV   -   Outcome   Death   Resolution   Resolution   Death   Resolution  \n \n Article data Kumaran et al. (54) Kataria et al. (55) AlHarmi et al. (56) Alwaeli et al. (57)     \n \n  Age   67   46   52   30   Sex   Female   Female   Female   Male   Past history   Laparotomy with intestinal resection for stenosis of the mesenteric artery, and secondary prophylaxis of thrombosis   -   Type 2 DM, HTN, hypothyroidism, and morbid obesity   -   Initial symptoms   Epigastric pain, diarrhea, and vomiting   Fever, dry cough, and dyspnea   Fever, dry cough, and dyspnea   Fever, dry cough, nausea, vomiting, abdominal pain, diarrhea, and progressive dyspnea   GIT symptoms   Yes   Yes   Yes   Yes   Abdominal pain   Epigastric   Epigastric pain irradiating to the back   Abdominal   Epigastric pain irradiating to the back   Pneumonia   No   Yes   Yes   Yes   SARS   No   Yes   Yes   Yes   Test to confirm COVID-19   RT-PCR   RT-PCR   RT-PCR   RT-PCR   Amylase, U/L   1,483   501   47   151   Lipase, U/L   Not done   1,541     1,022   CPR, mg/dL   15.8   2.51   1.09   -   Imaging test suggestive of acute pancreatitis   Abdominal CT   Abdominal CT   Abdominal CT   Abdominal CT   Triglycerides, mg/dL   310   153   168.3   133   Cholelithiasis or alcoholism   No   No   No   No   Diagnosis of pancreatitis   Modified Atlanta Classification   Imaging, clinical, and laboratory   Imaging and clinical   Imaging, clinical, and laboratory   CUM   -   -   -   -   Medication on admission   Meropenem, metronidazole, and clyndamycin   Azithromycin, ceftriaxone, and oxygen therapy   Dexamethasone, methylprednisolone, ceftriaxone, doxycycline, azithromycin, enoxaparin, vitamin D, zinc, fluticasone, salbutamol, ipratropium, and pantoprazole   -   Complications   NIV   NIV   NIV   OTI and mechanical ventilation   Outcome   Resolution   Resolution   Resolution   Resolution  \n \n Article data Alves et al. (58) Fernandes et al. (59) Purayil et al. (60) Patnaik et al. (61) Rabice et al. (62) \n \n  Age   56   36   58   29   36   Sex   Female   Female   Male   Male   Female   Past history     -   -   -   G4PC2 33-week gestation, obesity, pre-eclampsia, type 1 DM, and prior cholecystectomy   Initial symptoms   Dry cough, dyspnea, malaise, and abdominal pain   Fever, headache, and dyspnea   Fever, vomiting, and epigastric pain   Diffuse abdominal pain, irradiating to the back, fever, and dyspnea   Cough and fever   GIT symptoms   Yes   Yes   Yes   Yes   Yes   Abdominal pain   Epigastric   Epigastric   Epigastric   Diffuse, irradiating to the back   Abdominal   Pneumonia   Yes   Yes   Yes   Yes   Yes   SARS   Yes   No   No     No  \n \n Article data Alves et al. (58) Fernandes et al. (59) Purayil et al. (60) Patnaik et al. (61) Rabice et al. (62) \n \n  Test to confirm COVID-19   RT-PCR   RT-PCR   RT-PCR   RT-PCR   RT-PCR   Amylase, U/L   544   710   249   2,861   88   Lipase, U/L   2,993   640   >600   1,650   875   CRP, mg/dL   -   -   29   14.6   -   Imaging test suggestive of acute pancreatitis   Abdominal CT   Abdominal CT   No   Abdominal CT   No   Triglycerides, mg/dL   Not done   Not done   Normal   84   210   Cholelithiasis or alcoholism   No   No   No   No   No   Diagnosis of pancreatitis   Imaging, clinical, and laboratory   Imaging, clinical, and laboratory   Clinical and laboratory   Imaging, clinical, and laboratory   Clinical and laboratory   CUM   -   -   -   -   -   Medication on admission   -   -   Azithromycin and hydroxychloroquine   Meropenem and support   Dicloxacillin   Complications   OTI and mechanical ventilation   -   -   -   NIV and Caesarean section   Outcome   Resolution   Resolution   Resolution   Resolution   Resolution  \n \n Article data Bokhari et al. (63) Samies et al. (64) Samies et al. (64) Samies et al. (64) Kurihara et al. (65) \n \n  Age   32   15   11   16   55   Sex   Male   Male   Male   Female   Male   Past history   -   Obesity   Overweight   Prior pancreatitis   -   Initial symptoms   Fever, sore throat, productive cough, myalgia, and diarrhea   Vomiting, epigastric pain, fever, ageusia, and anosmia   Abdominal pain, headache, chills, intermittent hematochezia, and epistaxis   Nausea and epigastric abdominal pain   Pneumonia   GIT symptoms   Yes   Yes   Yes   Yes   ? - sedated patient   Abdominal pain   Epigastric irradiated to the back   Epigastric   Periumbilical   Epigastric irradiating to the back   ? - sedated patient   Pneumonia   Yes   Yes   Yes   No   Yes   SARS   No     No   No   Yes   Test to confirm COVID-19   RT-PCR   RT-PCR   RT-PCR   RT-PCR   RT-PCR   Amylase, U/L   672   Not done   215   Not done   252   Lipase, U/L   721   233   953   1,909   263   CPR, mg/dL   1.58   1.47   24.11   Not done   8.53   Imaging tests suggestive of acute pancreatitis   Abdominal CT   Abdominal CT   Abdominal CT   Abdominal ultrasound   Abdominal CT   Triglycerides, mg/dL   150   Not done   Not done   Not done   185   Cholelithiasis or alcoholism   No   No   No   Yes   No   Diagnosis of pancreatitis   Imaging, clinical, and laboratory   Imaging, clinical, and laboratory   Clinical and laboratory   Clinical and laboratory   Imaging, clinical, and laboratory   CUM   -   -   -   -   -   Medication on admission   -   -   Piperacillin-tazobactam   -   Lopinavir-ritonavir, azithromycin, and ceftriaxone   Complications   -   -   Acute appendicitis   -   OTI and mechanical ventilation, ECMO, and hemodialysis   Outcome   Resolution   Resolution   Resolution   Resolution   Resolution  \n \n Article data Bineshfar et al. (66) Hassani et al. (67) Bouali et al. (68) Schepis et al. (69) Ahmed et al. (70) \n \n  Age   14   78   60   67   47   Sex   Male   Female   Female   Female   Male   Past history   -   HTN and ischemic heart disease   -   -   -   Initial symptoms   Abdominal pain, nausea, and vomiting   Positional epigastric pain, nausea, and vomiting   Respiratory failure, diffuse abdominal pain, hematemesis, and melena   Fever, epigastric pain, and vomiting   Fever, sore throat, left-sided cervical edema, fatigue, and myalgia   GIT symptoms   Yes   Yes   Yes   Yes   Yes   Abdominal pain   Abdominal   Positional epigastric   Diffuse   Epigastric   Diffuse/RIF   Pneumonia   No   Yes   No   Yes   Yes   SARS   No   Yes   No   No   No   Test to confirm COVID-19   RT-PCR   RT-PCR   RT-PCR   RT-PCR   RT-PCR   Amylase, U/L   1,914   1,200   -   Normal   349   Lipase, U/L   Not done   1,450   627   Normal   >600   CRP, mg/dL   4   -   8   Increased   2.51   Imaging test suggestive of acute pancreatitis   Abdominal CT   Abdominal ultrasound   Abdominal CT   Abdominal CT   Abdominal CT   Triglycerides, mg/dL   Not done   Normal   Not done   Not done   Not done   Cholelithiasis or alcoholism   No   No   No   No   No   Diagnosis of pancreatitis   Atlanta Classification   Imaging, clinical, and laboratory   Balthazar Classification of abdominal CT   Analysis of pancreatic pseudocyst fluid containing SARS-CoV-2 RNA   Clinical and laboratory   CUM   -   Valsartan, clopidogrel, ASA, and atorvastatin   -   -   -   Medication on admission   -   Remdesivir and interferon beta-1b   -   -   Hydroxychloroquine, azithromycin, and cefuroxime   Complications   -   OTI and mechanical ventilation, kidney failure, and cardiorespiratory arrest   Laparotomy, gastrectomy, and cardiorespiratory arrest   Drainage of pancreatic pseudocyst   -   Outcome   Resolution   Death   Death   Resolution   Resolution  \n \n Article data Dietrich et al. (71) Chivato et al. (72)  ...Continuation  Table 2.  Key dat ...Continuation  Table 2.  Key data from the case reports a from the case reports   ...Continuation  Table 2.  Key data from the case reports   ...Continuation  Table 2.  Key data from the case reports    \n \n  Age   72 55  Sex  Male Male  Past history   Overweight and HTN  -  Initial symptoms  Nausea and mild abdominal pain Respiratory failure  GIT symptoms  Yes -  Abdominal pain  Mild -  Pneumonia  Yes Yes  SARS  Yes Yes  Test to confirm COVID-19  RT-PCR RT-PCR  Amylase, U/L  Not done Increased \n \n Article data Dietrich et al. (71) Chivato et al. (72) \n \n Lipase, U/L 185 Not done CRP, mg/dL 2.3 - Imaging test suggestive of acute pancreatitis Abdominal ultrasound Abdominal CT Triglycerides, mg/dL Not done Normal Cholelithiasis or alcoholism Cholelithiasis, without cholestasis Normal Diagnosis of pancreatitis Imaging, clinical, and laboratory Imaging and laboratorial CUM Beta-blocker - Medication on admission Ceftriaxone and clarithromycin Hydroxychloroquine, lopinavir, azithromycin, and methylprednisolone Complications OTI and mechanical ventilation Not available Outcome Resolution Resolution HTN: hypertension; HELLP: hemolysis, elevated liver enzymes, low platelet count; CKD: chronic kidney disease; GIT: gastrointestinal tract; SARS: severe acute respiratory syndrome; RT-PCR: reverse transcriptase polymerase chain reaction; CRP: C-reactive protein; CUM: continuous use medications; NIV: noninvasive ventilation; OTI: orotracheal intubation; ECMO: extracorporeal membrane oxygenation; DM:  diabetes mellitus ; MRI: magnetic resonance imaging; GERD: gastroesophageal reflux disease; ASA: acetylsalicylic acid; ? / - : information not available in the article.\nHTN: hypertension; HELLP: hemolysis, elevated liver enzymes, low platelet count; CKD: chronic kidney disease; GIT: gastrointestinal tract; SARS: severe acute respiratory syndrome; RT-PCR: reverse transcriptase polymerase chain reaction; CRP: C-reactive protein; CUM: continuous use medications; NIV: noninvasive ventilation; OTI: orotracheal intubation; ECMO: extracorporeal membrane oxygenation; DM:  diabetes mellitus ; MRI: magnetic resonance imaging; GERD: gastroesophageal reflux disease; ASA: acetylsalicylic acid; ? / - : information not available in the article.\nTable 3 Frequencies of data from the case reports   Mean 46.47 and median 47 Sex 22 female, 19 male, and one unknown Comorbidities, % 47.62 Abdominal pain, % 83.33 Pneumonia, % 80.95 SARS, % 38.1 Amylase mean, U/L 779.25 Lipase, U/L 1,230.88 2 C-reactive protein mean, mg/dL 9.73 Imaging suggestive of pancreatitis, % 85.71 Diagnostic classification as per Atlanta, % 73.8 (31/42) Complications, %* 52.38 Outcome, %* 80.95 in recovery and 11.9 deaths * Percentage excluding articles that do not mention complications or outcome. SARS: severe acute respiratory syndrome.\n* Percentage excluding articles that do not mention complications or outcome.\nSARS: severe acute respiratory syndrome.\nIn 23 studies, including 14 cohort studies, six literature reviews, one case-control study, and two prospective studies, 12 of them concluded there is some relation between COVID-19 and the pancreas or with acute pancreatitis; seven concluded no association but considered some data, and three concluded that there is no association.\nZippi et al., performed a literature review of 14 articles that proposed five theories for pancreatic damage in COVID-19. The first one is the direct damage of the virus, which is able to bind to ACE2 receptors, also expressed in the gastrointestinal tract and in the pancreas; the second one is the increase of pancreatic enzymes by kidney failure and by the lack of elimination of enzymes by the kidneys; the third is their translocation due to altered gastrointestinal permeability; the fourth, due to the use of pancreatic toxic drugs used in the treatment of COVID-19, such as lopinavir, ritonavir, tocilizumab, and baricitinib, among others; and the fifth, due to the cytokine storm caused by SARS-CoV-2, which would attack the pancreas, causing damage to the organ. ( 7 )  Along the same line, Hegyi et al., concluded that multiple organ failure that occurs in severe forms of COVID-19 resembles the lipotoxicity in severe acute pancreatitis. ( 15 )  Furthermore, they suggest that early supplementation with calcium and albumin helps to reduce lipotoxicity and subsequently counteract the cytokine storm, reducing severe outcomes. ( 15 )\nStill regarding pathophysiology, Rasch et al., pointed out that hyperlipasemia without typical signs of acute pancreatitis is a frequent finding in patients with COVID-19, due to the impaired microcirculation in severe patients, which would explain the increase in lipase rather than an extrapulmonary finding of the viral infection. ( 22 )  Goyal et al., and Rathi et al., also did not recommend associating high lipase levels with severity of pancreatic injury in COVID-19, but hyperlipasemia had a greater association with frequency of gastrointestinal signs and symptoms, a threefold increased risk for poor outcome, intensive care unit (ICU) admission, and mechanical ventilation. ( 32 , 33 )  This relation is not fully elucidated, but Akkus et al., suggested amylase and lipase can be used as indicators of disease activity and prognosis in patients with SARS-CoV-2, and can be included in their routine follow-up. ( 28 )\nWang et al., evaluated 52 patients admitted to Zhongnan Hospital of Wuhan University, from January to February 2020, and analyzed pancreatic injury as elevated lipase (>70U/L) and amylase (>90U/L). They identified a pattern of mild pancreatitis present in patients with COVID-19 pneumonia, but it may not be the result of direct viral involvement of pancreatic cells, since there was usually no positive clinical finding for acute pancreatitis. ( 35 )\nContrary to the studies described, McNabb-Baltar et al., showed hyperlipasemia (>60U/L) was not associated with severe forms of COVID-19 nor with worse clinical outcomes. Furthermore, they did not associate this finding with acute pancreatitis, since 48% of patients presented with hyperlipasemia, and none had criteria - whether laboratory or tomographic - for acute pancreatitis. ( 19 )\nTwo of the included studies diagnosed pancreatitis at autopsy examination. Lax et al., analyzed 11 bodies from patients infected with COVID-19, aged between 66 and 91 years. Acute pancreatitis was identified in four out of 11 patients, and in one third of them, no typical symptoms had been seen. ( 21 )  The other study was performed by Hanley et al., with bodies from eight SARS-CoV-2 positive patients, and 25% of them had acute pancreatitis. Among them, only one patient had microscopic findings of acute pancreatitis. As a limitation, the authors of the latter study could not confirm whether the findings of acute pancreatitis were due to iatrogenesis, comorbidities, or secondary infection. ( 25 )\nGubatan et al., in a cohort of eight patients, concluded that those with a history of pancreatitis were more susceptible to COVID-19; 7.8% of patients with prior pancreatitis had positive COVID-19 serology, whereas 2.8% of those had no prior pancreatitis. However, the authors did not associate an increased risk of pancreatic inflammation with SARS-CoV-2 infection, since none of the patients in the study had acute pancreatitis during viral infection. ( 27 )\nIdiopathic acute pancreatitis in the setting of COVID-19 has been identified in several studies. Inamdar et al., in a cohort of 32 patients infected with SARS-CoV-2 and diagnosed with acute pancreatitis by the Atlanta Classification, found the idiopathic form of pancreatitis to be the most common. Furthermore, they identified that Hispanic patients with acute pancreatitis were more likely to be diagnosed with COVID-19 than other ethnicities. ( 23 )  Corroborating these findings, Szatmary et al., concluded the endocrine pancreas is more vulnerable to COVID-19 infection, and male sex, abdominal pain, metabolic stress, and tomographic findings of pancreatic and duodenal inflammation with hepatic steatosis represent a distinction of pancreatitis in SARS-CoV-2. ( 26 )\nPandanaboyana et al., showed those with SARS-CoV-2 and acute pancreatitis had a significantly increased risk of developing moderate to severe or even severe acute pancreatitis, and a higher risk of secondary complications. They also had higher mortality compared to the group without the virus infection. However, this finding may have been due to the more advanced age, worse functionality score, and more severe and advanced stages of acute pancreatitis. ( 31 )  Dirweesh et al., also identified higher mortality in the SARS-CoV-2 infected group. In their cohort study, they diagnosed acute pancreatitis according to the Atlanta Classification, and found a higher incidence of multiple organ failure and persistent organ failure in this cohort. ( 24 )  In their prospective study, Akarsu et al., also showed that acute pancreatitis in patients with COVID-19 may deteriorate their clinical status and increase mortality. ( 16 )\nNot only in the adult group, Suchman et al., performed a retrospective study of patients under 18 years of age admitted to twelve New York City hospitals, between March and June 2020. Thirteen patients in the study were diagnosed with acute pancreatitis by the International Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPIRRE) criteria, ten of whom were diagnosed with idiopathic pancreatitis, with only two COVID-19 positive and the remainder negative. The authors suggest acute pancreatitis may occur in pediatric patients, and may be more common in those infected with SARS-CoV-2, particularly if there are associated gastrointestinal symptoms. ( 14 )\nRegarding imaging findings, Shiralkar et al., analyzed abdominal and thoracic CT and MRI scans of patients admitted with COVID-19 to the service included in the study. Ninety percent of them had pulmonary findings typical of COVID-19, and 25% of them had gastrointestinal findings of intestinal wall, pancreatitis, and cholecystitis. Among these patients, 70% had gastrointestinal symptoms upon admission, and 30% had them throughout their hospitalization. The authors call for early testing for SARS-CoV-2 in patients with typical or even atypical gastrointestinal symptoms, since it can lead to earlier diagnosis and isolation. ( 30 )  Along the same line, Gupta, in a meta-analysis, suggests associating clinical-radiological tests for the diagnosis of acute pancreatitis and COVID-19 and, furthermore, warns about exposure to peritoneal fluid, if a surgical approach is necessary, since this fluid or other peritoneal fluid may contain viral particles and be a source of contamination for the staff. ( 17 )\nThree of the studies analyzed demonstrated no relation between the virus and acute pancreatitis. Samanta et al., in five articles analyzed in systematic review, did not conclude about this relation. ( 29 )  McGuinness et al., compared hospitalization for acute abdomen, and there was no significant difference between 2019 and 2020 in severity of disease in patients with acute appendicitis (p=0.970), acute diverticulitis (p=0.333), or acute pancreatitis (p=0.803). However, this study was carried out in New Zealand, where there were few cases of COVID-19 cases during the study period. ( 34 )  Miró et al., found that hospital admission for acute pancreatitis as a presentation of COVID-19 is uncommon in emergency departments, and demonstrated that in-hospital mortality does not differ between patients with acute pancreatitis, with or without concomitant viral infection. However, mortality in COVID-19 patients was higher in the setting of acute pancreatitis, perhaps due to the severity of presenting both diseases at the same time. ( 20 )\nRegarding published case reports, Juhász et al., pointed out that not all of them follow the case report guidelines, often skipping steps in the investigation of acute pancreatitis or not giving importance to the effect of several drugs used in the treatment of COVID-19 at hospital settings, which have also been described as a cause of acute drug-induced pancreatitis. ( 18 )\nThe 39 case reports included in this study (some with case series) totaled 42 patients. Not all studies presented complete data of the clinical case and diagnosis of acute pancreatitis.\nMost studies diverge as to diagnostic criteria, with three reports based on the Atlanta Classification; three on the modified Atlanta Classification; two on the modified Glasgow coma scale for acute pancreatitis; 17 joining clinical, laboratory, and imaging data; seven only with abdominal computed tomography (CT); two with clinical diagnosis; five with clinical and laboratory data, and one with clinical data and abdominal CT. Among the signs of acute pancreatitis on imaging, in 33 of 42 cases there were descriptions of suggestive findings, such as pancreatic edema, blurring of peripancreatic fat, necrosis, pancreatic pseudocyst, among others. Only three studies presented cases of patients with a history of mild alcoholism  ( 41 )  and cholelithiasis. ( 64 , 71 )\nAmong the characteristics of patients (n=42), 19 had comorbidities, sometimes combined, such as obesity or overweight (8), hypertension (10), type 1 or 2  diabetes mellitus  (six), and hypercholesterolemia (one). The female patients appeared subtly more numerous than males - 22 and 19 cases, respectively. The mean age was 46.64 years, with a minimum of 11 years and a maximum of 78 years, with a median of 47 years and a mode of 67 years (four patients), and 36 years (four patients). Only seven studies cited the continuous use of medications, that is, beta-blocker, valsartan, clopidogrel, acetylsalicylic acid (ASA), atorvastatin, trastuzumab, losartan, metformin, insulin, omeprazole, nifedipine, carvedilol, levothyroxine, alendronate, cyanocobalamin (Vitamina B12), and alprazolam.\nAmong the initial symptoms that led the patient to seek medical care, gastrointestinal (64.28%), respiratory (47.61%), and fever (54.76%) problems were the most common. Regarding abdominal pain, it was typical in the epigastric region, in a band-like area, irradiating to the back (12/42); only epigastric (13/42); diffuse (8/42); in the right iliac fossa (1/42), periumbilical (1/42), or absent (3/42); four studies did not mention abdominal pain.\nThe diagnosis of pneumonia was made in 34 patients, 16 of whom had SARS  per se . Only one article did not mention the diagnosis of COVID-19, ( 39 )  and, in the others, it was made by reverse transcriptase polymerase chain reaction (RT-PCR).\nRegarding laboratory tests, 28 studies included serum amylase results, with a mean of 779.25U/L (the highest being 3,568U/L); 32 included serum lipase, with a mean of 1,230.88U/L (the highest being 8,352U/L); C-reactive protein was cited in 25 articles, with a mean of 9.73mg/dL (the highest being 29mg/dL); and triglycerides were performed in 15 articles, with a mean of 191.54mg/dL (the highest being 310mg/dL)-nine articles did not cite the triglyceride result, but described it as normal.\nThe medications used during hospitalization were cited in 18 of the reports included in the study. There were antibiotics, antimalarials, antivirals, corticosteroids, anticoagulants, bronchodilators, zinc, vitamin D, pantoprazole, and ondansetrone.\nRegarding the evolution of cases, the most frequent complications were the need for non-invasive ventilation (NIV) with some oxygen supplementation (11/42), followed by the need for orotracheal intubation (10/42). Other noteworthy complications were kidney failure and need for hemodialysis (5/42), use of extracorporeal membrane oxygenation (ECMO) (3/42), and cardiac arrest (3/42). Among other less frequent events in the sample were the need to conduct term (1/42) and premature (1/42) labor, diabetic ketoacidosis (1/42), pulmonary thromboembolism (1/42), refractory distributive shock (1/42), acute appendicitis concomitant with pancreatitis (1/42), pancreatic pseudocyst and its drainage (1/42), and laparotomy approach due to extensive necrosis (1/42). Two reports did not provide complications. The outcome of the cases was mostly resolution of the condition (34/42), with five deaths. Three reports did not provide the outcome.\n\nThe pancreas as an extrapulmonary site in SARS-CoV-2 infection is still a doubt among several researchers. An interesting number of case reports suggested this association, but there is no pattern among them, which makes analysis and comparison among studies difficult. In addition, there is a small number of studies that are not case reports, but in those found in this research, most of them concluded there is some association.\nThe hypothesis that the increasing diagnosis of acute idiopathic pancreatitis is related to COVID-19 as a possible infectious etiology, is due to the known ability of other viruses to infect and inflame the gland. ( 13 )  Therefore, associating the two causes could be plausible. Furthermore, SARS-CoV-2 causes infection in cells by binding its glycoprotein (spike protein S) to the ACE2 receptor, which is present in various tissues, including the pancreas. ( 4 )  It is also known that ACE2 participates in the regulation of metabolism through its action in the gland, allowing better insulin secretion and glucose homeostasis. ( 73 )  Interestingly, the expression of SARS-CoV-2 in the pancreatic tissue, in addition to supporting the hypothesis it causes acute pancreatitis, can also cause insulin-dependent  diabetes mellitus  by destroying the pancreatic islets. ( 74 )  Additionally, several studies have demonstrated pancreatic involvement with histopathological analysis in autopsy of patients with COVID-19. ( 9 , 10 )\nIn contrast, another pathological study that also identified viral RNA in the pancreas analyzed the SARS-CoV-2 RT-PCR Ct (RT-PCR-cycle threshold) values. ( 11 ) These values are used to measure the prognosis of the disease. Low values correlated with a greater risk of a serious evolution and higher mortality and, therefore, worse prognosis. ( 75 )  In the study, higher Ct values were found in non-respiratory tissues, and no active viral replication or hybrid virus capture was identified in them. It was concluded that, although RT-PCR for SARS-CoV-2 was positive in non-respiratory tissues, such as the pancreas, this finding might be due to residual viral RNA in the blood of these organs. The much-feared cytokine storm and multiple organ failure, which occur in severe forms of COVID-19, resemble the lipotoxicity process in severe acute pancreatitis. ( 15 )  Thus, some authors suggested that in a patient in moderate to severe state, pancreatitis may be either by systemic inflammation of COVID-19 or by the virus itself in the pancreas. Severe cases of COVID-19 are strongly related to comorbidities, mainly hypertension, followed by  diabetes mellitus , coronary disease, and obesity, among others. ( 3 )  Of the 42 patients described in the included reports, 19 presented at least one of these diseases, which may support the theory of exacerbated systemic inflammation in response to the virus that caused the pancreatic injury, and not the direct viral action in the gland.\nAcute pancreatitis is a multifactorial inflammatory disease of the pancreas, and the major concern is the progression to severe forms, with high morbidity and mortality. ( 76 )\nThe diagnosis is made using the 2012 Atlanta Classification, which includes typical abdominal pain (acute and persistent epigastric pain, of strong intensity, irradiating to the back), serum lipase or serum amylase increased by at least three times the normal limit, and imaging findings compatible with acute pancreatitis on contrast-enhanced CT, MRI, or abdominal ultrasound. The diagnosis is established with at least two of the three criteria listed, and the disease is classified as mild, moderate, or severe, according to the patient’s evolution within 48 hours. This criterion is accepted worldwide, leading to a consensus for the diagnosis of the disease, as well as better differentiation between the presentations (acute peripancreatic collection, pseudocyst, necrosis, and walled-off necrosis), and guidance for the most appropriate treatment. ( 77 )\nAmong the case reports included in this study, only six explicitly stated that the Atlanta Classification was used, which makes it difficult to compare with the others that cited diagnosis only by imaging tests (seven studies) or clinical examination (one), because the universally established criteria were not respected, leading to hasty conclusions. Although 23 studies did not directly cite the Atlanta Classification, they respected the guideline by presenting at least two criteria, used other severity scales, such as Ranson, or modified Glasgow for acute pancreatitis, also accepted internationally. The diagnosis, in general, was well performed, with 31 studies against eight others without the Atlanta Classification. However, given the important systemic manifestations in SARS-CoV-2 infection, it is necessary to use the globally accepted criteria to properly validate the diagnosis of acute pancreatitis in a potentially severe patient. This is an important orientation, both to guide the management of disease, for statistical consideration, and for studies on viral infectivity in the pancreas, the characteristics of symptoms, and their evolution.\nIt is interesting to note there was a greater increase in lipase compared to amylase. Lipase is more sensitive than amylase for the diagnosis of acute pancreatitis, since it has a higher peak and stays elevated longer. However, lipase can be elevated for several reasons, such as cytotoxic effects of COVID-19 or increased intestinal permeability, as in critical illness in intense care unit (ICU), diabetes, use of opioids, and diarrhea. ( 66 , 78 )\nSeveral authors have noted divergences in diagnoses of acute pancreatitis, mainly because hyperlipasemia draws so much attention. Rasch et al., warned this finding is a result from impaired microcirculation rather than an extrapulmonary finding of viral infection  per se. ( 22 )  McNabb-Baltar et al., further demonstrated hyperlipasemia was not related to acute pancreatitis, since 48% of patients in the study with this finding did not present with laboratory or tomographic criteria to definitely make diagnosis. ( 19 )  Along the same line, in his meta-analysis Gupta also alerted to the need of complementation of increased serum lipase with clinical and radiological findings. ( 17 )  Wang et al., also reported increased pancreatic enzymes and associated this finding with pancreatic injury, but could not conclude whether there was a relation with direct viral damage to the gland. ( 35 )  However, in this latter study, the classification of pancreatic injury did not follow the Atlanta Classification, with mean normal value or slightly elevated values of lipase and amylase - 77U/L and 86U/L, respectively.\nTherefore, it is even more important to use the Atlanta Classification, since in the presence of SARS-CoV-2 infection, hyperlipasemia, or hyperamylasemia may occur, with or without clinical or radiological findings of acute pancreatitis. These findings should be supplemented with clinical and imaging examinations, to elucidate the diagnosis and adequately treat the patients.\nOn the other hand, three studies ( 28 , 32 , 33 )  suggested hyperlipasemia can be used as a prognostic value in critically-ill patients with COVID-19. They demonstrated that higher values were associated with increased risk for poor outcomes, ICU admission, intubation, and mechanical ventilation time. Although McNabb-Baltar et al., ( 19 )  concluded otherwise, these other three studies have relevant numbers of patients and similar results, which help to clarify the role of increased serum lipase in these cases. Thus, dosing the enzyme, especially upon admission of critically-ill patients, may contribute to more targeted care, as a simple and low-cost test that would act as a prognostic factor. Given the serious situation in several hospitals around the world, including Brazil, at the peak of the pandemic, with ICU capacity rates above 80% in several states, ( 79 )  dosing of lipase could help in the allocation of patients and predict the care they may need, such as ICU admission and mechanical ventilation, improving hospital organization and patient management.\nThe fact that most patients described in the included reports sought medical care for gastrointestinal symptoms (64.28%), typical or atypical of acute pancreatitis, is a worrisome fact. Most presented only with extrapulmonary symptoms, had respiratory symptoms late in their hospitalization, or presented suggestive tomographic findings by chance, such as ground-glass opacities, in the absence of respiratory symptoms. These facts have led teams to test RT-PCR for SARS-CoV-2 in these cases. Dietrich et al., described the case of a 72-year-old patient who presented with nausea and abdominal pain for 7 days. On investigation, an abdominal ultrasound showed cholelithiasis with no signs of cholestasis, and pancreatic parenchyma barely visible and apparently heterogeneous. Endoscopy and transesophageal ultrasound showed heterogeneous pancreatic tissue, with no focal masses, biliary duct with no signs of intraluminal or papillary calculi, suggesting acute non-biliary pancreatitis and no alcoholic etiology, since there was no past history of alcoholism. The patient progressively worsened until, on the fifth day of hospitalization, his chest CT scan showed bilateral ground-glass opacities. He was immediately isolated and subsequently confirmed with COVID-19. ( 71 )  Thus, it is important to reinforce the use of personal protective equipment, even when treating patients without classic symptoms of the virus, since this may be an extrapulmonary manifestation of the virus or an early presentation.\nThe gastrointestinal tract is a known focus of SARS-CoV-2. In March 2020, Tian et al., found a 3% to 79% incidence of patients with gastrointestinal symptoms in SARS-CoV-2 infection, including anorexia (39.9% to 50.2%), diarrhea (2% to 49%), vomiting (3.6% to 66.7%), nausea (1% to 29.4%), abdominal pain (2.2% to 6%), and gastrointestinal bleeding (4% to 13.7%). Diarrhea was the most common symptom in both adults and children, and was observed before and after diagnosis. More alarmingly, adults and children could present such symptoms without manifesting any respiratory complaints. ( 5 ) These facts agree with those on  table 2 , in which most patients sought medical care without respiratory complaints, and were later diagnosed with the virus. ( 6 , 38 , 41 - 45 , 48 , 51 , 54 , 60 , 64 , 66 , 67 , 69 , 71 )\nThe typical presentation of acute pancreatitis, with abdominal pain, nausea, and vomiting, fits into the most common set of gastrointestinal symptoms of COVID-19. Furthermore, diarrhea as an initial symptom was present in four of the reports included in this study, raising an alarm for the differential diagnosis of acute pancreatitis with SARS-CoV-2, or, in addition, alerting to the concomitant presence of these diseases, which, by causing intense systemic inflammation, increase morbidity and mortality in these patients. It is extremely important to apply the Atlanta Classification to diagnose acute pancreatitis and test for the virus, to identify these patients early, assist in their management, and protect the staff and other patients hospitalized at the same service for other causes.\nFollowing the same reasoning, there are studies proving the presence of the virus in the peritoneal and peripancreatic fluid, and in pancreatic pseudocysts, sometimes in viral concentrations even higher than in the respiratory tract, poses a risk for infection of the staff during invasive procedures. ( 17 , 40 , 54 , 69 ) Therefore, more protective measures should be taken if the surgical management of these patients is necessary.\nThe measures of care for acute pancreatitis initially include aggressive volume replacement and oral fasting, and in COVID-19, depending on the status of the patient, such measures would not be taken. ( 12 )  In addition, some drugs can be toxic to the pancreas and even cause drug-induced pancreatitis, such as antivirals (lopinavir and ritonavir), antipyretics, tocilizumab, and baricitinib. ( 7 )  In the case reports presented on  table 2 , only 18 of them cited drugs used during hospitalization - among them lopinavir (5/19), ritonavir (4/19), and tocilizumab (1/19); in four patients the concomitant use of lopinavir and ritonavir was used, and in one of them the combined use of these three drugs. Early detection of patients with acute pancreatitis and SARS-CoV-2 is necessary to avoid the occurrence of drug-induced pancreatitis, although rare, in patients already susceptible to severe systemic inflammation, or worsening of an already installed acute pancreatitis.\n\nThe literature is still divergent regarding pancreatic involvement in COVID-19. There are several confounding factors in the diagnosis of acute pancreatitis during concomitant infection by SARS-CoV-2, but the currently available information offers important warnings. First, in relation to the clinic, since in most cases the search for the health service was for abdominal pain, which should raise the suspicion of acute pancreatitis and other gastrointestinal diseases, as well as SARS-CoV-2 infection. Second, regarding the use of hyperlipasemia as a risk factor for admission to the intensive care unit, and use of mechanical ventilation. Third, the importance of following the Atlanta Classification or modified Atlanta Classification in patients with COVID-19 with increased pancreatic enzymes and/or gastrointestinal symptoms. Similarly, patients presenting with acute pancreatitis should be tested for COVID-19, since the clinical picture may be similar.\nThus, it is possible to identify early two diseases that can develop into serious and even fatal conditions, and to detect and isolate these patients more quickly. Additional studies are needed to prove the virus is capable of infecting the pancreas, but the data analyzed here are an important starting point.","source_license":"CC-BY-4.0","license_restricted":false}