Digestive System Involvement During Coronavirus Disease 2019; the Newest Clinical Features and Potential Mechanisms

  • Aida Najafi Kashkooli Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Parisa Jooya Department of Family Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • Farzaneh Navari Department of emergency medicine, Imam Hossein Educational Hospital, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
  • Neda Gorjizadeh Department of Gastroenterology, Tehran University of Medical Sciences, Tehran, Iran
  • Maryam Poudineh School of Medicine, Mashhad Azad University, Mashhad, Iran
  • Neda Pouralimohamadi Department of Family Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • Asma Asadian Clinical Research Development Unit, 9Dey Educational Hospital Torbat Heydariyeh University Of Medical Sciences, Torbat Heydariyeh, Iran
  • Hamidreza Sabet Department of Medical Journalism, Faculty of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
Keywords: COVID-19, Digestive System, Gastrointestinal Tract, Liver Injury, Pancreas


The coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been recognized as a worldwide pandemic and mostly affects the respiratory system. A considerable proportion of patients; however, might also experience gastrointestinal (GI) manifestations. Several investigations have assessed GI and hepatic involvement in this disease, although the mechanisms of these involvements in relation to the progression of COVID-19 remain unclear. This review summarized the clinical observations and the main mechanisms behind GI, liver, and pancreatic involvement among COVID-19 patients.


Vakili S, Akbari H, Jamalnia S. Clinical and Laboratory findings on the differences between h1n1 influenza and coronavirus disease-2019 (covid-19): focusing on the treatment approach. Clin Pulm Med. 2020;27(4):87-93.


Vakili S, Savardashtaki A, Jamalnia S, Tabrizi R, Nematollahi MH, Jafarinia M, et al. Laboratory findings of COVID-19 infection are conflicting in different age groups and pregnant women: a literature review. Archives of Medical Research. 2020;51(7):603-7.


PMid:32571605 PMCid:PMC7287430

Zaim S, Chong JH, Sankaranarayanan V, Harky A. COVID-19 and Multiorgan Response. Curr Probl Cardiol. 2020;45(8):100618.


PMid:32439197 PMCid:PMC7187881

Zhong P, Xu J, Yang D, Shen Y, Wang L, Feng Y, et al. COVID-19-associated gastrointestinal and liver injury: clinical features and potential mechanisms. Sig Transduct Target Ther. 2020;5(1):1-8.


PMid:33139693 PMCid:PMC7605138

Singal CMS, Jaiswal P, Seth P. SARS-CoV-2, more than a respiratory virus: its potential role in neuropathogenesis. ACS Chem Neurosci. 2020;11(13):1887-99.



Mao R, Qiu Y, He JS, Tan JY, Li X-H, Liang J, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(7):667-78.



Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5(5):428-30.



Tian Y, Rong L, Nian W, He Y. gastrointestinal features in COVID‐19 and the possibility of faecal transmission. Aliment Pharmacol Ther. 2020;51(9):843-51.


PMid:32222988 PMCid:PMC7161803

Ungaro RC, Sullivan T, Colombel J-F, Patel G. What should gastroenterologists and patients know about COVID-19? Clin Gastroenterol Hepatol. 2020;18(7):1409-11.


PMid:32197957 PMCid:PMC7156804

Cheung KS, Hung IF, Chan PP, Lung K, Tso E, Liu R, 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(1):81-95.


PMid:32251668 PMCid:PMC7194936

Fang D, Ma J, Guan J, Wang M, Song Y, Tian D, et al. Manifestations of digestive system of hospitalized patients with coronavirus disease 2019 in Wuhan, China: a single-center descriptive study. Chinese Journal of Digestion. 2020:151-6.

Cha MH, Regueiro M, Sandhu DS. Gastrointestinal and hepatic manifestations of COVID-19: A comprehensive review. World J Gastroenterol. 2020;26(19):2323.


PMid:32476796 PMCid:PMC7243653

Aziz M, Haghbin H, Lee-Smith W, Goyal H, Nawras A, Adler DG. Gastrointestinal predictors of severe COVID-19: systematic review and meta-analysis. Ann Gastroenterol. 2020;33(6):615.


PMid:33162738 PMCid:PMC7599357

Parasa S, Desai M, Chandrasekar VT, Patel HK, Kennedy KF, Roesch T, et al. Prevalence of gastrointestinal symptoms and fecal viral shedding in patients with coronavirus disease 2019: a systematic review and meta-analysis. JAMA Netw Open. 2020;3(6):e2011335.


PMid:32525549 PMCid:PMC7290409

Dong ZY, Xiang BJ, Jiang M, Sun MJ, Dai C. The prevalence of gastrointestinal symptoms, abnormal liver function, digestive system disease and liver disease in COVID-19 infection: a systematic review and meta-analysis. J Clin Gastroenterol. 2021;55(1):67.


PMid:33116063 PMCid:PMC7713642

Zarifian A, Zamiri Bidary M, Arekhi S, Rafiee M, Gholamalizadeh H, Amiriani A, et al. Gastrointestinal and hepatic abnormalities in patients with confirmed COVID‐19: A systematic review and meta‐analysis. J Med Virol. 2021;93(1):336-50.


PMid:32681674 PMCid:PMC7405277

Kumar VCS, Mukherjee S, Harne PS, Subedi A, Ganapathy MK, Patthipati VS, et al. Novelty in the gut: a systematic review and meta-analysis of the gastrointestinal manifestations of COVID-19. BMJ Open Gastroenterol. 2020;7(1):e000417.


PMid:32457035 PMCid:PMC7252994

Tariq R, Saha S, Furqan F, Hassett L, Pardi D, Khanna S. Prevalence and Mortality of COVID-19 Patients With Gastrointestinal Symptoms: A Systematic Review and Meta-analysis. Mayo Clin Proc. 2020;95(8):1632-48.


PMid:32753138 PMCid:PMC7284248

Rokkas T. Gastrointestinal involvement in COVID-19: a systematic review and meta-analysis. Ann Gastroenterol. 2020;33(4):355.


PMid:32624655 PMCid:PMC7315709

Li J, Huang DQ, Zou B, Yang H, Hui WZ, Rui F, et al. Epidemiology of COVID‐19: A systematic review and meta‐analysis of clinical characteristics, risk factors, and outcomes. J Med Virol. 2021;93(3):1449-58.


PMid:32790106 PMCid:PMC7436673

Kumar A, Arora A, Sharma P, Anikhindi SA, Bansal N, Singla V, et al. Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis. Indian J Gastroenterol. 2020;39(3):268-84.


PMid:32749643 PMCid:PMC7399358

Shehab M, Alrashed F, Shuaibi S, Alajmi D, Barkun A. Gastroenterological and hepatic manifestations of patients with COVID-19, prevalence, mortality by country, and intensive care admission rate: systematic review and meta-analysis. BMJ Open Gastroenterol. 2021;8(1):e000571.


PMid:33664052 PMCid:PMC7934201

Merola E, Armelao F, De Pretis G. Prevalence of gastrointestinal symptoms in coronavirus disease 2019: a meta-analysis. JAMA Netw Open. 2020;83:603-15.

Dorrell RD, Dougherty MK, Barash EL, Lichtig AE, Clayton SB, Jensen ET. Gastrointestinal and hepatic manifestations of COVID‐19: A systematic review and meta‐analysis. JGH Open. 2021;5(1):107-15.


PMid:33363257 PMCid:PMC7753450

Wang H, Qiu P, Liu J, Wang F, Zhao Q. The liver injury and gastrointestinal symptoms in patients with coronavirus disease 19: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2020;44(5):653-61.


PMid:32418852 PMCid:PMC7214284

Sultan S, Altayar O, Siddique SM, Davitkov P, Feuerstein JD, Lim JK, et al. AGA institute rapid review of the gastrointestinal and liver manifestations of COVID-19, meta-analysis of international data, and recommendations for the consultative management of patients with COVID-19. Gastroenterology. 2020;159(1):320-34.e27.


PMid:32407808 PMCid:PMC7212965

Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831-3.e3.


PMid:32142773 PMCid:PMC7130181

Liang W, Feng Z, Rao S, Xiao C, Xue X, Lin Z, et al. Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus. Gut. 2020;69(6):1141-3.



Zhang H, Kang Z, Gong H, Xu D, Wang J, Li Z, et al. Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process. Gut. 2020;69(6):1010-8.



Lin L, Jiang X, Zhang Z, Huang S, Zhang Z, Fang Z, et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69(6):997-1001.


PMid:32241899 PMCid:PMC7316116

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-80. e8.


PMid:32142651 PMCid:PMC7102627

Ye Q, Wang B, Zhang T, Xu J, Shang S. The mechanism and treatment of gastrointestinal symptoms in patients with COVID-19. Am J Physiol Gastrointest Liver Physiol. 2020;319(2):G245-52.


PMid:32639848 PMCid:PMC7414235

Akbari H, Tabrizi R, Lankarani KB, Aria H, Vakili S, Asadian F, et al. The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. Life Sci. 2020;258:118167.


PMid:32735885 PMCid:PMC7387997

Hu B, Huang S, Yin L. The cytokine storm and COVID‐19. J Med Virol. 2021;93(1):250-6.


PMid:32592501 PMCid:PMC7361342

De Lucena TMC, Da Silva Santos AF, De Lima BR, De Albuquerque Borborema ME, De Azevêdo Silva J. Mechanism of inflammatory response in associated comorbidities in COVID-19. Diabetes Metab Syndr. 2020;14(4):597-600.


PMid:32417709 PMCid:PMC7215143

Moghaddam Tabrizi F, Rasmi Y, Hosseinzadeh E, Rezaei S, Balvardi M, Kouchari MR, et al. Diabetes is associated with higher mortality and severity in hospitalized patients with COVID-19. Excli J. 2021;20:444-53.

Hoseinyazdi M, Esmaeilian S, Jahankhah R, Teimouri A, Sherbaf FG, Rafiee F, et al. Clinical, laboratory, and chest CT features of severe versus non-severe pediatric patients with COVID-19 infection among different age groups. BMC Infect Dis. 2021;21(1):560.


PMid:34118894 PMCid:PMC8196295

Zarei F, Jalli R, Iranpour P, Sefidbakht S, Soltanabadi S, Rezaee M, et al. Differentiation of Chest CT Findings Between Influenza Pneumonia and COVID-19: Interobserver Agreement Between Radiologists. Acad Radiol. 2021;28(10):1331-8.


PMid:34024714 PMCid:PMC8112282

Zhang Y, Geng X, Tan Y, Li Q, Xu C, Xu J, et al. New understanding of the damage of SARS-CoV-2 infection outside the respiratory system. Biomed Pharmacother. 2020;127:110195.


PMid:32361161 PMCid:PMC7186209

Wong SH, Lui RN, Sung JJ. Covid‐19 and the digestive system. J Gastroenterol Hepatol. 2020;35(5):744-8.



Yu W, Ou X, Liu X, Zhang S, Gao X, Cheng H, et al. ACE2 contributes to the maintenance of mouse epithelial barrier function. Biochem Biophys Res Commun. 2020;533(4):1276-82.


PMid:33097186 PMCid:PMC7576438

Budden KF, Gellatly SL, Wood DL, Cooper MA, Morrison M, Hugenholtz P, et al. Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol. 2017;15(1):55-63.



De Oliveira GLV, Oliveira CNS, Pinzan CF, De Salis LVV, Cardoso CRdB. Microbiota modulation of the gut-lung axis in COVID-19. Front Immunol. 2021;12:6354712.


PMid:33717181 PMCid:PMC7945592

Hunt RH, East JE, Lanas A, Malfertheiner P, Satsangi J, Scarpignato C, et al. COVID-19 and gastrointestinal disease: implications for the gastroenterologist. Dig Dis. 2021;39(2):119-39.


PMid:33040064 PMCid:PMC7705947

Zhang D, Li S, Wang N, Tan H-Y, Zhang Z, Feng Y. The cross-talk between gut microbiota and lungs in common lung diseases. Front Microbiol. 2020;11:301.


PMid:32158441 PMCid:PMC7052046

Wang J, Li F, Wei H, Lian Z-X, Sun R, Tian Z. Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation. J Exp Med. 2014;211(12):2397-410.


PMid:25366965 PMCid:PMC4235643

Stenstad H, Ericsson A, Johansson-Lindbom B, Svensson M, Marsal J, Mack M, et al. Gut-associated lymphoid tissue-primed CD4+ T cells display CCR9-dependent and-independent homing to the small intestine. Blood. 2006;107(9):3447-54.



Papadakis KA, Prehn J, Nelson V, Cheng L, Binder SW, Ponath PD, et al. The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system. J Immunol. 2000;165(9):5069-76.



Crowe CR, Chen K, Pociask DA, Alcorn JF, Krivich C, Enelow RI, et al. Critical role of IL-17RA in immunopathology of influenza infection. J Immunol. 2009;183(8):5301-10.


PMid:19783685 PMCid:PMC3638739

Delgado-Gonzalez P, Gonzalez-Villarreal CA, Roacho-Perez JA, Quiroz-Reyes AG, Islas JF, Delgado-Gallegos JL, et al. Inflammatory effect on the gastrointestinal system associated with COVID-19. World J Gastroenterol. 2021;27(26):4160.


PMid:34326616 PMCid:PMC8311540

Maconi G, Bosetti C, De Monti A, Boyapati RK, Shelton E, Piazza N, et al. Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population. Dig Liver Dis. 2021;53(3):263-70.


PMid:33483259 PMCid:PMC7762705

Neurath MF. COVID-19 and immunomodulation in IBD. Gut. 2020;69(7):1335-42.


PMid:32303609 PMCid:PMC7211083

Holmer A, Singh S. Overall and comparative safety of biologic and immunosuppressive therapy in inflammatory bowel diseases. Expert Rev Clin Immunol. 2019;15(9):969-79.


PMid:31322018 PMCid:PMC6813772

Beaugerie L, Rahier J-F, Kirchgesner J. Predicting, preventing, and managing treatment-related complications in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2020;18(6):1324-35.e2.



Cavezzi A, Troiani E, Corrao S. COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review. Clin Pract. 2020;10(2):1271.


PMid:32509258 PMCid:PMC7267810

Singhal R, Shah YM. Oxygen battle in the gut: Hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine. J Biol Chem. 2020;295(30):10493-505.


PMid:32503843 PMCid:PMC7383395

Paniz‐Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, et al. Central nervous system involvement by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). J Med Virol. 2020;92(7):699-702.


PMid:32314810 PMCid:PMC7264598

Trottein F, Sokol H. Potential causes and consequences of gastrointestinal disorders during a SARS-CoV-2 infection. Cell Rep. 2020;32(3):107915.


PMid:32649864 PMCid:PMC7332457

Mao R, Liang J, Shen J, Ghosh S, Zhu L, Yang H, et al. Chinese society of IBD, Chinese elite IBD union; Chinese IBD quality care Evaluation Center Committee. Implications of COVID-19 for patients with pre-existing digestive diseases. Lancet Gastroenterol Hepatol. 2020;5(5):426-8.



Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20.


PMid:32109013 PMCid:PMC7092819

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497-506.



Zhang Y, Zheng L, Liu L, Zhao M, Xiao J, Zhao Q. Liver impairment in COVID‐19 patients: A retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int. 2020;40(9):2095-103.



Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, et al. COVID-19: Abnormal liver function tests. J Hepatol. 2020;73(3):566-74.



PMid:32298767 PMCid:PMC7194951

Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting interleukin-6 signaling in clinic. Immunity. 2019;50(4):1007-23.



Kishimoto T. Interleukin-6: from basic science to medicine-40 years in immunology. Annu Rev Immunol. 2005;23:1.



Zhan K, Liao S, Li J, Bai Y, Lv L, Yu K, et al. Risk factors in patients with COVID-19 developing severe liver injury during hospitalisation. Gut. 2021;70(3):628-9.


PMid:32571973 PMCid:PMC7873415

Wang Y, Liu S, Liu H, Li W, Lin F, Jiang L, et al. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol. 2020;73(4):807-16.



Wu H-T, Chuang Y-W, Huang C-P, Chang M-H. Loss of angiotensin converting enzyme II (ACE2) accelerates the development of liver injury induced by thioacetamide. Exp Anim. 2018;67(1):41-9.


PMid:28845018 PMCid:PMC5814313

Schett G, Sticherling M, Neurath MF. COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Nat Rev Immunol. 2020;20(5):271-2.


PMid:32296135 PMCid:PMC7186927

Glowacka I, Bertram S, Müller MA, Allen P, Soilleux E, Pfefferle S, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol. 2011;85(9):4122-34.


PMid:21325420 PMCid:PMC3126222

Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med. 2020;383(6):590-2.


PMid:32402155 PMCid:PMC7240771

Sonzogni A, Previtali G, Seghezzi M, Grazia Alessio M, Gianatti A, Licini L, et al. Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations. Liver Int. 2020;40(9):2110-6.


PMid:32654359 PMCid:PMC7404964

Pirola CJ, Sookoian S. COVID-19 and ACE2 in the liver and gastrointestinal tract: putative biological explanations of sexual dimorphism. Gastroenterology. 2020;159(4):1620.


PMid:32348773 PMCid:PMC7194954

Lien T-C, Sung C-S, Lee C-H, Kao H-K, Huang Y-C, Liu C-Y, et al. Characteristic features and outcomes of severe acute respiratory syndrome found in severe acute respiratory syndrome intensive care unit patients. J Crit Care. 2008;23(4):557-64.


PMid:19056023 PMCid:PMC7125607

Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ, et al. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A. 2004;101(44):15748-53.


PMid:15496474 PMCid:PMC524836

Wang K, Chen W, Zhang Z, Deng Y, Lian J-Q, Du P, et al. CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal Transduct Target Ther. 2020;5(1):1-10.


PMid:33277466 PMCid:PMC7714896

Fara A, Mitrev Z, Rosalia RA, Assas BM. Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines. Open Biol. 2020;10(9):200160.


PMid:32961074 PMCid:PMC7536084

Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355-62.


PMid:32376901 PMCid:PMC7201395

Feng G, Zheng KI, Yan QQ, Rios RS, Targher G, Byrne CD, et al. COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies. J Clin Transl Hepatol. 2020;8(1):18.


PMid:32274342 PMCid:PMC7132016

Rasouli J, Ciric B, Imitola J, Gonnella P, Hwang D, Mahajan K, et al. Expression of GM-CSF in T cells is increased in multiple sclerosis and suppressed by IFN-β therapy. J Immunol. 2015;194(11):5085-93.


PMid:25917097 PMCid:PMC4433790

Crayne CB, Albeituni S, Nichols KE, Cron RQ. The immunology of macrophage activation syndrome. Front Immunol. 2019;10:119.


PMid:30774631 PMCid:PMC6367262

Yang L, Han Y, Nilsson-Payant BE, Gupta V, Wang P, Duan X, et al. A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids. Cell stem Cell. 2020;27(1):125-36.e7.


PMid:32579880 PMCid:PMC7303620

Banales JM, Huebert RC, Karlsen T, Strazzabosco M, LaRusso NF, Gores GJ. Cholangiocyte pathobiology. Nat Rev Gastroenterol Hepatol. 2019;16(5):269-81.


PMid:30850822 PMCid:PMC6563606

Mederacke I, Hsu CC, Troeger JS, Huebener P, Mu X, Dapito DH, et al. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun. 2013;4(1):1-11.


PMid:24264436 PMCid:PMC4059406

Geier A, Fickert P, Trauner M. Mechanisms of disease: mechanisms and clinical implications of cholestasis in sepsis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(10):574-85.



Peralta C, Jiménez-Castro MB, Gracia-Sancho J. Hepatic ischemia and reperfusion injury: effects on the liver sinusoidal milieu. J Hepatol. 2013;59(5):1094-106.



Horvatits T, Trauner M, Fuhrmann V. Hypoxic liver injury and cholestasis in critically ill patients. Curr Opin Crit Care. 2013;19(2):128-32.



Dar WA, Sullivan E, Bynon JS, Eltzschig H, Ju C. Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms. Liver Int. 2019;39(5):788-801.


PMid:30843314 PMCid:PMC6483869

Horvatits T, Drolz A, Trauner M, Fuhrmann V. Liver injury and failure in critical illness. Hepatology. 2019;70(6):2204-15.



Sprent J, Tough DF. T cell death and memory. Science. 2001;293(5528):245-8.



Kulkarni AV, Kumar P, Tevethia HV, Premkumar M, Arab JP, Candia R, et al. Systematic review with meta‐analysis: liver manifestations and outcomes in COVID‐19. Aliment Pharmacol Ther. 2020;52(4):584-99.


PMid:32638436 PMCid:PMC7361465

Oyelade T, Alqahtani J, Canciani G. Prognosis of COVID-19 in patients with liver and kidney diseases: an early systematic review and meta-analysis. Trop Med Infect Dis. 2020;5(2):80.


PMid:32429038 PMCid:PMC7345004

Kundal V, Qureshi S, Mahajan S. Chronic Liver Disease: Etiological Spectrum in Adults. JK Science. 2017;19(3):145-9.

Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61(6):1385-96.



Cichoż-Lach H, Michalak A. Liver injury in the era of COVID-19. World J Gastroenterol. 2021;27(5):377.


PMid:33584070 PMCid:PMC7856845

Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N. Acetaminophen-induced hepatotoxicity: a comprehensive update. J Clin Transl Hepatol. 2016;4(2):131.


Akinci E, Cha M, Lin L, Yeo G, Hamilton MC, Donahue CJ, et al. Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics. BioRxiv. 2020.


Chiou H-E, Liu C-L, Buttrey MJ, Kuo H-P, Liu H-W, Kuo H-T, et al. Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers. Chest. 2005;128(1):263-72.


PMid:16002945 PMCid:PMC7094379

Breining P, Frølund AL, Højen JF, Gunst JD, Staerke NB, Saedder E, et al. Camostat mesylate against SARS‐CoV‐2 and COVID‐19-Rationale, dosing and safety. Basic Clin Pharmacol Toxicol. 2021;128(2):204-12.



Montefusco L, Ben Nasr M, D'Addio F, Loretelli C, Rossi A, Pastore I, et al. Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection. Nat Metab. 2021;3(6):774-85.



Qadir MMF, Bhondeley M, Beatty W, Gaupp DD, Doyle-Meyers LA, Fischer T, et al. SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes. JCI insight. 2021;6(16):e151551.


PMid:34241597 PMCid:PMC8410013

Geravandi S, Mahmoudi-Aznaveh A, Azizi Z, Maedler K, Ardestani A. SARS-CoV-2 and pancreas: a potential pathological interaction? Trends Endocrinol Metab. 2021;32(11):842-5.


PMid:34373155 PMCid:PMC8302839

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(9):2128-30.e2.


PMid:32334082 PMCid:PMC7194639

Masamune A, Watanabe T, Kikuta K, Shimosegawa T. Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis. Clin Gastroenterol Hepatol. 2009;7(11):S48-54.



Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020;53:25-32.


PMid:32446778 PMCid:PMC7211650

Muniraj T, Dang S, Pitchumoni CS. PANCREATITIS OR NOT?-Elevated lipase and amylase in ICU patients. J Crit Care. 2015;30(6):1370-5.



How to Cite
Najafi Kashkooli , A., Jooya , P., Navari , F., Gorjizadeh, N., Poudineh, M., Pouralimohamadi , N., Asadian, A., & Sabet , H. (2022). Digestive System Involvement During Coronavirus Disease 2019; the Newest Clinical Features and Potential Mechanisms. Galen Medical Journal, 11, e2569. https://doi.org/10.31661/gmj.v11i.2569
Review Article