Abstract

COVID-19 is an infectious disease caused by novel coronavirus SARS-CoV-2, a betacoronavirus comprised of single-stranded ribonucleic acid (RNA), the first time reported in December 2019 as pneumonia with unknown etiology in Wuhan City in China. It is a very important current problem for public health worldwide. A typical clinical course includes dyspnoea, dry cough and fever. In the presented paper we conducted the literature review and described the most important facts within the current state of knowledge about symptomatology and pathophysiology of gastrointestinal dysfunction in the course of COVID-19. Data about prevalence of gastrointestinal symptoms in the course of COVID-19 show wide divergence in the cited literature. Generally, the most common reported digestive symptoms were loss of appetite, nausea and vomiting. Liver injury in the course of COVID-19 is also an important and not well understood problem. The virus has high affinity to cells containing angiotensin- -converting enzyme 2 (ACE2) protein. Digestive symptoms of COVID-19 may be associated with ACE2 expression in epithelial cells in upper oesophagus, ileum and colon. Previous scientific reports have elucidated the role of ACE2 in modulating intestinal inflammation and diarrhoea.

References

• 1. Agostoni A., Cugno M.: The kinin system: Biological mechanismsand clinical implications. Recenti Prog. Med., 2001; 92: 764–773
  Google Scholar
• 2. Assiri A., Al-Tawfiq J.A., Al-Rabeeah A.A., Al-Rabiah F.A., Al-Hajjar S., Al-Barrak A., Flemban H., Al-Nassir W.N., Balkhy H.H.,Al-Hakeem R.F., Makhdoom H.Q., Zumla A.I., Memish Z.A.: Epidemiological,demographic, and clinical characteristics of 47 cases ofMiddle East respiratory syndrome coronavirus disease from SaudiArabia: A descriptive study. Lancet Infect. Dis., 2013; 13: 752–761
  Google Scholar
• 3. Bailey E.S., Fieldhouse J.K., Choi J.Y., Gray G.C.: A mini review ofthe zoonotic threat potential of influenza viruses, coronaviruses,adenoviruses, and enteroviruses. Front. Public Health, 2018; 6: 104
  Google Scholar
• 4. Boeckmans J., Rodrigues R.M., Demuyser T., Piérard D., VanhaeckeT., Rogiers V.: COVID 19 and drug induced liver injury: A problemof plenty or a petty point? Arch. Toxicol., 2020; 94: 1367–1369
  Google Scholar
• 5. Bombardini T., Picano E.: Angiotensin-converting enzyme 2 asthe molecular bridge between epidemiologic and clinical featuresof COVID-19. Can. J. Cardiol., 2020; 36: 784.e1–784.e2
  Google Scholar
• 6. Byrnes J.J., Gross S., Ellard C., Connolly K., Donahue S., PicarellaD.: Effects of the ACE2 inhibitor GL1001 on acute dextran sodiumsulfate-induced colitis in mice. Inflamm. Res., 2009; 58: 819–827
  Google Scholar
• 7. Chai X., Hu L., Zhang Y., Han W., Lu Z., Ke A., Zhou J., Shi G., FangN., Fan J., Cai J., Fan J., Lan F.: Specific ACE2 expression in cholangiocytesmay cause liver damage after 2019-nCoV infection. bioRxiv,2020; DOI: 10.1101/2020.02.03.931766
  Google Scholar
• 8. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., WangJ., Liu Y., Wei Y., Xia J., Yu T., Zhang X., Zhang L.: Epidemiologicaland clinical characteristics of 99 cases of 2019 novel coronaviruspneumonia in Wuhan, China: A descriptive study. Lancet, 2020;395: 507–513
  Google Scholar
• 9. Cheung K.S., Hung I.F., Chan P.P., Lung K.C., Tso E., Liu R., NgY.Y., Chu M.Y., Chung T.W., Tam A.R., Yip C.C., Leung K.H., FungA.Y., Zhang R.R., Lin Y., et al.: Gastrointestinal manifestations ofSARS-CoV-2 infection and virus load in fecal samples from a HongKong cohort: Systematic review and meta-analysis. Gastroenterology,2020; 159: 81–95
  Google Scholar
• 10. D’Amico F., Baumgart D.C., Danese S., Peyrin-Biroulet L.: Diarrheaduring COVID-19 infection: Pathogenesis, epidemiology,prevention, and management. Clin. Gastroenterol. Hepatol., 2020;18: 1663–1672
  Google Scholar
• 11. Del Rio C., Malani P.N.: COVID-19 –new insights on a rapidlychanging epidemic. JAMA, 2020; 323: 1339–1340
  Google Scholar
• 12. Dziewas R., Warnecke R., Zürcher P., Schefold J.C.: Dysphagiain COVID-19 –multilevel damage to the swallowing network? Eur.J. Neurol., 2020; 27: e46–e47
  Google Scholar
• 13. El-Hashim A.Z., Renno W.M., Raghupathy R., Abduo H.T.,Akhtar S., Benter I.F.: Angiotensin-(1-7) inhibits allergic inflammation,via the MAS1 receptor, through suppression of ERK1/2- andNF-κB-dependent pathways. Br. J. Pharmacol., 2012; 166: 1964–1976
  Google Scholar
• 14. Elfiky A.A.: Anti-HCV, nucleotide inhibitors, repurposingagainst COVID-19. Life. Sci., 2020; 248: 117477
  Google Scholar
• 15. Fan Z., Chen L., Li J., Cheng X., Yang J., Tian C., Zhang Y.,Huang S., Liu Z., Cheng J.: Clinical features of COVID-19-relatedliver functional abnormality. Clin. Gastroenterol. Hepatol., 2020;18: 1561–1566
  Google Scholar
• 16. Gao J., Tian Z., Yang X.: Breakthrough: Chloroquine phosphatehas shown apparent efficacy in treatment of COVID-19 associatedpneumonia in clinical studies. Biosci. Trends., 2020; 14: 72–73
  Google Scholar
• 17. Golias C., Charalabopoulos A., Stagikas D., Charalabopoulos K.,Batistatou A.: The kinin system – bradykinin: Biological effects andclinical implications. Multiple role of the kinin system – bradykinin.Hippokratia, 2007; 11: 124–128
  Google Scholar
• 18. Goodell J.W.: COVID-19 and finance: Agendas for future research.Finance Res. Lett., 2020; 35: 101512 19 Goyal P., Choi J.J., Pinheiro L.C., Schenck E.J., Chen R., JabriA., Satlin M.J., Campion T.R. Jr., Nahid M., Ringel J.B., HoffmanK.L., Alshak M.N., Li H.A., Wehmeyer G.T., Rajan M., et al.: Clinicalcharacteristics of Covid-19 in New York City. N. Engl. J. Med.,2020; 382: 2372–2374
  Google Scholar
• 19. pandemic. Gastroenterology 2020; 159: 739–758
  Google Scholar
• 20. Gu J., Gong E., Zhang B., Zheng J., Gao Z., Zhong Y., Zou W.,Zhan J., Wang S., Xie Z., Zhuang H., Wu B., Zhong H., Shao H., FangW., et al.: Multiple organ infection and the pathogenesis of SARS.J. Exp. Med., 2005; 202: 415–424
  Google Scholar
• 21. Gu J., Han B., Wang J.: COVID-19: Gastrointestinal manifestationsand potential fecal-oral transmission. Gastroenterology,2020; 158: 1518–1519
  Google Scholar
• 22. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X., Liu L.,Shan H., Lei C.L., Hui D.S., Du B., Li L.J., Zeng G., Yuen K.Y., ChenR.C., et al.: Clinical characteristics of coronavirus disease 2019 inChina. N. Engl. J. Med., 2020; 382: 1708–1720
  Google Scholar
• 23. Heymann D.L., Shindo N., WHO Scientific and Technical AdvisoryGroup for Infectious Hazards: COVID-19: What is next forpublic health? Lancet, 2020; 395: 542–545
  Google Scholar
• 24. Hilgenfeld R., Peiris M.: From SARS to MERS: 10 years of researchon highly pathogenic human coronaviruses. Antiviral Res.,2013; 100: 286–295
  Google Scholar
• 25. Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., HerrlerT., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., Müller M.A., Drosten C., Pöhlmann S.: SARS-CoV-2 cell entry dependson ACE2 and TMPRSS2 and is blocked by a clinically provenprotease inhibitor. Cell, 2020; 181: 271–280
  Google Scholar
• 26. Holshue M.L., DeBolt C., Lindquist S., Lofy K.H., Wiesman J.,Bruce H., Spitters C., Ericson K., Wilkerson S., Tural A., Diaz G.,Cohn A., Fox L., Patel A., Gerber S.I., et al.: First case of 2019 novelcoronavirus in the United States. N. Engl. J. Med., 2020; 382: 929–936
  Google Scholar
• 27. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., FanG., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wie Y., Wu W., et al.: Clinicalfeatures of patients infected with 2019 novel coronavirus in Wuhan,China. Lancet, 2020; 395: 497–506
  Google Scholar
• 28. Jin Y., Yang H., Ji W., Wu W., Chen S., Zhang W., Duan G.: Virology,epidemiology, pathogenesis, and control of COVID-19. Viruses,2020; 12: 372
  Google Scholar
• 29. Jose R.J., Manuel A.: COVID-19 cytokine storm: The interplaybetween inflammation and coagulation. Lancet Respir. Med., 2020;8: e46–e47
  Google Scholar
• 30. Khajah M.A., Fateel M.M., Ananthalakshmi K.V., Luqmani Y.A.:Anti-inflammatory action of angiotensin 1-7 in experimental colitis.PLoS One, 2016; 11: e0150861
  Google Scholar
• 31. Kwan Y.W., Leung C.W., Chiu M.C.: Diarrhoea as the presentingsign in an adolescent suffering from severe acute respiratorysyndrome. Eur. J. Pediatr., 2005; 164: 227–230
  Google Scholar
• 32. Li G., He X., Zhang L., Ran Q., Wang J., Xiong A., Wu D., Chen F.,Sun J., Chang C.: Assessing ACE2 expression patterns in lung tissuesin the pathogenesis of COVID-19. J. Autoimmun., 2020; 112: 102463
  Google Scholar
• 33. Li T., Zhang Y., Gong C., Wang J., Liu B., Shi L., Duan J.: Prevalenceof malnutrition and analysis of related factors in elderlypatients with COVID-19 in Wuhan, China. Eur. J. Clin. Nutr., 2020;74: 871–875
  Google Scholar
• 34. Li Y., Xia L.: Coronavirus disease 2019 (COVID-19): Role of chestCT in diagnosis and management. Am. J. Roentgenol., 2020; 214:1280–1286
  Google Scholar
• 35. Li Y.C., Bai W.Z., Hirano N., Hayashida T., Hashikawa T.: Coronavirusinfection of rat dorsal root ganglia: Ultrastructural characterizationof viral replication, transfer, and the early responseof satellite cells. Virus Res., 2012; 163: 628–635
  Google Scholar
• 36. Liang W., Feng Z., Rao S., Xiao C., Xue X., Lin Z., Zhang Q., QiW.: Diarrhoea may be underestimated: A missing link in 2019 novelcoronavirus. Gut, 2020; 69: 1141–1143
  Google Scholar
• 37. Lin L., Jiang X., Zhang Z., Huang S., Zhang Z., Fang Z., Gu Z.,Gao L., Shi H., Mai L., Liu Y., Lin X., Lai R., Yan Z., Li X., et al.: Gastrointestinalsymptoms of 95 cases with SARS-CoV-2 infection.Gut, 2020; 69: 997–1001
  Google Scholar
• 38. Ling Y., Xu S.B., Lin Y.X., Tian D., Zhu Z.Q., Dai F.H., Wu F., SongZ.G., Huang W., Chen J., Hu B.J., Wang S., Mao E.Q., Zhu L., ZhangW.H., et al.: Persistence and clearance of viral RNA in 2019 novelcoronavirus disease rehabilitation patients. Chin. Med. J., 2020;133: 1039–1043
  Google Scholar
• 39. Lu H., Stratton C.W., Tang Y.W.: Outbreak of pneumonia of unknownethiology in Wuhan, China: The mystery and the miracle.J. Med. Virol., 2020; 92: 401–402
  Google Scholar
• 40. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., SongH., Huang B., Zhu N., Bi Y., Ma X., Zhan F., Wang L., Hu T., et al.:Genomic characterisation and epidemiology of 2019 novel coronavirus:Implications for virus origins and receptor binding. Lancet,2020; 395: 565–574
  Google Scholar
• 41. Luo S., Zhang X., Xu H.: Don’t overlook digestive symptomsin patients with 2019 novel coronavirus disease (COVID-19). Clin.Gastroenterol. Hepatol., 2020; 18: 1636–1637
  Google Scholar
• 42. Mantovani A., Beatrice G., Dalbeni A.: Coronavirus disease 2019and prevalence of chronic liver disease: A meta-analysis. Liver Int.,2020; 40: 1316–1320
  Google Scholar
• 43. Mao R., Qiu Y., He J.S., Tan J.Y., Li X.H., Liang J., Shen J., ZhuL.R., Chen Y., Iacucci M., Ng S.C., Ghosh S., Chen M.H.: Manifestationsand prognosis of gastrointestinal and liver involvement inpatients with COVID-19: A systematic review and meta-analysis.Lancet Gastroenterol. Hepatol., 2020; 5: 667–678
  Google Scholar
• 44. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S.,Manson J.J., HLH Across Speciality Collaboration, UK: COVID-19:Consider cytokine storm syndromes and immunosuppression. Lancet,2020; 395: 1033–1034
  Google Scholar
• 45. Ong J., Young B.E., Ong S.: COVID-19 in gastroenterology:A clinical perspective. Gut, 2020; 69: 1144–1145
  Google Scholar
• 46. Pagliaro P., Penna C.: Rethinking the renin-angiotensin systemand its role in cardiovascular regulation. Cardiovasc. DrugsTher., 2005; 19: 77–87
  Google Scholar
• 47. Pan L., Mu M., Yang P., Sun Y., Wang R., Yan J., Li P., Hu B., WangJ., Hu C., Jin Y., Niu X., Ping R., Du Y., Li T., et al.: Clinical characteristicsof COVID-19 patients with digestive symptoms in Hubei,China: A descriptive, cross-sectional, multicenter study. Am. J.Gastroenterol., 2020; 115: 766–773
  Google Scholar
• 48. Rodrigues Prestes T.R., Rocha N.P., Miranda A.S., Teixeira A.L.,Simoes-E-Silva A.C.: The anti-inflammatory potential of ACE2/angiotensin-(1-7)/Mas receptor axis: Evidence from basic and clinicalresearch. Curr. Drug Targets, 2017; 18: 1301–1313
  Google Scholar
• 49. Schmaier A.H.: The kallikrein-kinin and the renin-angiotensinsystems have a multilayered interaction. Am. J. Physiol. Regul. Integr.Comp. Physiol., 2003; 285: R1–R13
  Google Scholar
• 50. Skoretz S.A., Flowers H.L., Martino R.: The incidence of dysphagiafollowing endotracheal intubation: A systematic review.Chest, 2010; 137: 665–673
  Google Scholar
• 51. Sultan S., Lim J.K., Altayar O., Davitkov P., Feuerstein J.D., SiddiqueS.M., Falck-Ytter Y., El-Serag H.B., AGA Institute: AGA rapidrecommendations for gastrointestinal procedures during the COVID-
  Google Scholar
• 52. Sun J., Aghemo A., Forner A., Valenti L.: COVID-19 and liverdisease. Liver Int., 2020; 40: 1278–1281
  Google Scholar
• 53. Tassorelli C., Mojoli F., Baldanti F., Bruno R., Benazzo M.: COVID-19: What if the brain had a role in causing the deaths? Eur. J.Neurol., 2020; 27: e41–e42
  Google Scholar
• 54. Tian Y., Rong L., Nian W., He Y.: Review article: Gastrointestinalfeatures in COVID-19 and the possibility of faecal transmission.Aliment. Pharmacol. Ther., 2020; 51: 843–851
  Google Scholar
• 55. Vaira LA, Salzano G, Deiana G, De Riu G.: Anosmia and ageusia:Common findings in COVID-19 patients. Laryngoscope, 2020;130: 1787
  Google Scholar
• 56. van de Veerdonk F.L., Netea M.G., van Deuren M., van der MeerJ.W., de Mast Q., Brüggemann R.J., van der Hoeven H.: Kallikreinkininblockade in patients with COVID-19 to prevent acute respiratorydistress syndrome. eLife, 2020; 9: e57555
  Google Scholar
• 57. Wang F., Wang H., Fan J., Zhang Y., Wang H., Zhao Q.: Pancreaticinjury patterns in patients with coronavirus disease 19 pneumonia.Gastroenterology, 2020; 159: 367–370
  Google Scholar
• 58. Weiss S.R., Leibowitz J.L.: Coronavirus pathogenesis. Adv.Virus Res., 2011; 81: 85–164
  Google Scholar
• 59. Wong S.H., Lui R.N., Sung J.J.: Covid-19 and the digestive system.J. Gastroenterol. Hepatol., 2020; 35: 744–748
  Google Scholar
• 60. Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.L.,Abiona O., Graham B.S., McLellan J.S.: Cryo-EM structure of the2019-nCoV spike in the prefusion conformation. Science, 2020;367: 1260–1263
  Google Scholar
• 61. Xie H., Zhao J., Lian N., Lin S., Xie Q., Zhuo H.: Clinical characteristicsof non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: A retrospective study. Liver Int., 2020;40: 1321–1326
  Google Scholar
• 62. Xie Y., Cao S., Dong H., Li Q., Chen E., Zhang W., Yang L., Fu S.,Wang R.: Effect of regular intravenous immunoglobulin therapyon prognosis of severe pneumonia in patients with COVID-19. J.Infect., 2020; 81: 318–356
  Google Scholar
• 63. Xu L., Liu J., Lu M., Yang D., Zheng X.: Liver injury duringhighly pathogenic human coronavirus infections. Liver Int., 2020;40: 998–1004
  Google Scholar
• 64. Xu X., Han M., Li T., Sun W., Wang D., Fu B., Zhou Y., ZhengX., Yang Y., Li X., Zhang X., Pan A., Wei H.: Effective treatment ofsevere COVID-19 patients with tocilizumab. Proc. Natl. Acad. Sci.USA, 2020; 117: 10970–10975
  Google Scholar
• 65. Yao T.T., Qian J.D., Zhu W.Y., Wang Y., Wang G.Q.: A systematicreview of lopinavir therapy for SARS coronavirus and MERS coronavirus– a possible reference for coronavirus disease‐19 treatmentoption. J. Med. Virol., 2020; 92: 556–563
  Google Scholar
• 66. Zhai P., Ding Y., Wu X., Long J., Zhong Y., Li Y.: The epidemiology,diagnosis and treatment of COVID-19. Int. J. Antimicrob.Agents, 2020; 55: 105955
  Google Scholar
• 67. Zhang C., Shi L., Wang F.S.: Liver injury in COVID-19: Managementand challenges. Lancet Gastroenterol. Hepatol., 2020;5: 428–430
  Google Scholar
• 68. Zhang Y., Zheng L., Liu L., Zhao M., Xiao J., Zhao Q.: Liver impairmentin COVID-19 patients: A retrospective analysis of 115cases from a single centre in Wuhan city, China. Liver Int., 2020;40: 2095–2103
  Google Scholar
• 69. Zhu F.C., Li Y.H., Guan X.H., Hou L.H., Wang W.J., Li J.X., WuS.P., Wang B.S., Wang Z., Wang L., Jia S.Y., Jiang H.D., Wang L., JiangT., Hu Y., et al.: Safety, tolerability, and immunogenicity ofa recombinant adenovirus type-5 vectored COVID-19 vaccine:A dose-escalation, open-label, non-randomized, first-in-humantrial. Lancet, 2020; 395: 1845–1854
  Google Scholar

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