COVID-19-associated diarrhea

• Alexey M. Shchikota
• Irena V. Pogonchenkova
• Elena A. Turova
• Antonina V. Starodubova
• Natalya V. Nosova

Abstract

In addition to the typical clinical picture of respiratory symptoms and intoxication, the SARS-CoV-2 virus is also characterized by a gastroenterotropic effect. Diarrhea is one of the most common gastroenterological symptoms of COVID -19 and is detected, according to the various authors, in 2-49.5% of cases, including children. The presence of diarrhea aggravates the patient’s clinical condition, limits the possibility of carrying out the necessary diagnostic manipulations, and complicates the selection of therapy. The article provides an overview of the scientific literature on the formation of diarrheal syndrome in patients with COVID-19.

Objective. Analysis of scientific publications studying the pathogenesis, incidence, clinical features, aspects of diagnosis and therapy of diarrhea in patients with COVID-19.

Material and methods. A search was made for scientific publications on the electronic resources PubMed, Google Scholar and eLIBRARY.ru.

Results. The pathogenesis of diarrhea in a new coronavirus infection is complex and includes, among other things, the effect of the virus on the angiotensin-converting enzyme 2 receptors, inducing an inflammatory process in the gastrointestinal tract mucosa, neurotropic effect on the autonomic regulation of intestinal motor activity, disturbance of the colon microbiota, liver and pancreas damage. Another important pathogenetic aspect of diarrhea in COVID-19 is iatrogenic one, i.e. a side effect of drugs used in the treatment of a new coronavirus infection and its complications, and the activation of opportunistic clostridial intestinal flora against the background of antibiotic therapy. The variety of pathogenetic mechanisms of diarrheal syndrome formation allows us to speak of “COVID-associated diarrhea” as an independent clinical phenomenon characteristic for the new coronavirus infection. Mandatory diagnostic algorithm of a patient with COVID-19 and diarrhea is the fecal analysis test for toxins Cl. difficile, while the possibility of endoscopic examinations during the pandemic is limited. Compliance with the hygiene measures, diet correction and nutritional support, rational antibiotic therapy of COVID-19 complications, careful use of antiperistaltic antidiarrheal drugs, nonspecific therapy (antiviral, rehydration, adsorbents) are considered as the main therapeutic approaches for diarrheal syndrome against the background of COVID-19. The administration of probiotics and antibacterials should be considered in case of confirmed clostridial co-infection.

Conclusion. Diarrhea is a frequent clinical manifestation of COVID-19 and can affect the course of the disease. The complex genesis of diarrheal syndrome requires further study of therapeutic strategies and nutritional support for patients after COVID-19.

Keywords:COVID-19, diarrhea, Clostridioides difficile, antibiotic, gastrointestinal tract, probiotics

30. Guotao L., Xingpeng Z., Zhihui D., Huirui W. SARS-CoV-2 infection presenting with hematochezia. Med Mal Infect. 2020; 50 (3): 293–6. DOI: https://doi.org/10.1016/j.medmal.2020.03.005

31. D'Amico F., Baumgart D.C., Danese S., Peyrin-Biroulet L. Diarrhea during COVID-19 infection: pathogenesis, epidemiology, prevention, and management. Clin Gastroenterol Hepatol. 2020; 18 (8): 1663–72. DOI: https://doi.org/10.1016/j.cgh.2020.04.001

32. Holshue M.L., DeBolt C., Lindquist S., et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020; 382 (10): 929–36. DOI: https://doi.org/10.1056/NEJMoa2001191

33. Lu X., Zhang L., Du H., Zhang J., Li Y.Y., Qu J., et al.; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 infection in children. N Engl J Med. 2020; 382 (17): 1663–5. DOI: https://doi.org/10.1056/NEJMc2005073

34. Han C., Duan C., Zhang S., Spiegel B., Shi H., Wang W., et al. Digestive symptoms in COVID-19 patients with mild disease severity: clinical presentation, stool viral RNA testing, and outcomes. Am J Gastroenterol. 2020; 115 (6): 916–23. DOI: https://doi.org/10.14309/ajg.0000000000000664

35. Zheng S., Fan J., Yu F., et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ (Clin Res Ed). 2020; 369: 1443. DOI: https://doi.org/10.1136/bmj.m1443

36. American Society for Gastrointestinal Endoscopy; 2020. ASGE Releases Recommendations for Endoscopy Units in the Era of COVID-19. URL: https://www.asge.org/docs/default-source/default-document-library/press-release_impact-of-covid-19-on-endoscopy.pdf (date of access July 07, 2021)

37. Martínez E.P.-C. Recommendations by the SEPD and AEG, both in general and on the operation of gastrointestinal endoscopy and gastroenterology units, concerning the current SARS-CoV-2 pandemic. Rev Esp Enferm Dig. 2020; 112 (4): 319–22. DOI: https://doi.org/10.17235/reed.2020.7052/2020

38. Association «Endoscopic Society “REndO”» (Association «REndO»). Moscow Research Institute of Epidemiology and Microbiology named after G.N. Gabrichevsky. Organization of work of endoscopic units and provision of epidemiological safety of endoscopic interventions in conditions of epidemic of new coronavirus infection. Temporary recommendations (the version 4 dated 27.04.2020). Klinicheskaya endoskopiya [Clinical Endoscopy]. 2020; 1 (56): 49–65. URL: https://endoexpert.ru/dokumenty-i-prikazy/vremennye-rekomendatsii-fbun-mniiem-im-gabrichevskogo-i-rendo-versiya-4-0-dlya-endoskopicheskikh-otd/ (in Russian)

39. Song Y., Zhang M., Yin L., Wang K., Zhou Y., Zhou M., et al. COVID-19 treatment: close to a cure? A rapid review of pharmacotherapies for the novel coronavirus (SARS-CoV-2). Int J Antimicrob Agents. 2020; 56 (2): 106080. DOI: https://doi.org/10.1016/j.ijantimicag.2020.106080

40. Zhang X., Tang C., Tian D., Hou X., Yang Y. Management of digestive disorders and procedures associated with COVID-19. Am J Gastroenterol. 2020; 115 (8): 1153–5. DOI: https://doi.org/10.14309/ajg.0000000000000728

41. Gupta A., Cifu A.S., Khanna S. Diagnosis and treatment of Clostridium difficile infection. JAMA. 2018; 320: 1031–2. DOI: https://doi.org/10.1001/jama.2018.12194

42. Ianiro G., Mullish B.H., Kelly C.R., et al. Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic. Gut. 2020; 69 (9): 1555–63. DOI: https://doi.org/10.1136/gutjnl-2020-321829

43. Wang C., Wang S., Li D., Wei D.Q., Zhao J., Wang J. Human intestinal defensin 5 inhibits SARS-CoV-2 invasion by cloaking ACE2. Gastroenterology. 2020; 159 (3): 1145–7.e4. DOI: https://doi.org/10.1053/j.gastro.2020.05.015

44. Sundararaman A., Ray M., Ravindra P.V., Halami P.M. Role of probiotics to combat viral infections with emphasis on COVID-19. Appl Microbiol Biotechnol. 2020; 104 (19): 8089–104. DOI: https://doi.org/10.1007/s00253-020-10832-4

45. Jeżewska-Frąckowiak J., Łubkowska B., Sobolewski I., Skowron P.M. Probiotics in the times of COVID-19. Acta Biochim Pol. 2021; 68: 393–8. DOI: https://doi.org/10.18388/abp.2020_5691

46. Kanauchi O., Andoh A., AbuBakar S., Yamamoto N. Probiotics and paraprobiotics in viral infection: clinical application and effects on the innate and acquired immune systems. Curr Pharm Des. 2018; 24: 710–7. DOI: https://doi.org/10.2174/1381612824666180116163411

47. Mulak A. The impact of probiotics on interactions within the microbiota-gut-lung triad in COVID-19. Int J Food Sci Nutr. 2021; 4: 577–8. DOI: https://doi.org/10.1080/09637486.2020.1850651

48. Verma A., Xu K., Du T., Zhu P., Liang Z., Liao S., et al. Expression of human ACE2 in Lactobacillus and beneficial effects in diabetic retinopathy in mice. Mol Ther Methods Clin Dev. 2019; 14: 161–70. DOI: https://doi.org/10.1016/j.omtm.2019.06.007

49. Lee N.-K., Paik H.-D. Prophylactic effects of probiotics on respiratory viruses including COVID-19: a review. Food Sci Biotechnol. 2021; 30: 1–9. DOI: https://doi.org/10.1007/s10068-021-00913-z

50. Hawryłkowicz V., Lietz-Kijak D., Kaźmierczak-Siedlecka K., Sołek-Pastuszka J., Stachowska L., Folwarski M., et al. Patient nutrition and probiotic therapy in COVID-19: what do we know in 2021? Nutrients. 2021; 13 (10): 3385. DOI: https://doi.org/10.3390/nu13103385

51. Louca P., Murray B., Klaser K., Graham M.S., Mazidi M., Leeming E.R., et al. Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app. BMJ Nutr Prev Health. 2021; 4 (1): 149–57. DOI: https://doi.org/10.1136/bmjnph-2021-000250

52. Kullar R., Johnson S., McFarland L.V., Goldstein E.J.C. Potential roles for probiotics in the treatment of COVID-19 patients and prevention of complications associated with increased antibiotic use. Antibiotics. 2021; 4: 408. DOI: https://doi.org/10.3390/antibiotics10040408

53. Hegazy M.A.E., Ashoush O.A., Hegazy M.T., Wahba M., Lithy R.M., Abdel-Hamid H.M., et al. Beyond probiotic legend: ESSAP gut microbiota health score to delineate SARS-COV-2 infection severity. Br J Nutr. 2021; June 7: 1–10. DOI: https://doi.org/10/1017/S0007114521001926

54. WHO. Coronavirus disease (COVID-19) advice for the public: myth busters [Electronic resource]. WHO, 2021. URL: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters (date of access July 07, 2021)

55. British Dietetic Association. COVID-19/coronavirus – advice for the general public: «Can I boost my immune system through my diet?». 16 Mar 2020 [updated April 14 2020]. BDA. URL: https://www.bda.uk.com/resource/covid-19-corona-virus-advice-for-the-generalpublic.html (date of access July 07, 2021)

56. Barazzoni R., Bischoff S.C., Breda J., Wickramasinghe K., Krznaric Z., Nitzan D., et al. ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection. Clin Nutr. 2020; 39: 1631–8. DOI: https://doi.org/10.1016/j.clnu.2020.03.022

57. Yisak H., Ewunetei A., Kefale B., Mamuye M., Teshome F., Ambaw B., et al. Effects of vitamin D on COVID-19 infection and prognosis: a systematic review. Risk Manag Healthc Policy. 2021; 14: 31–8. DOI: https://doi.org/10.2147/RMHP.S291584

58. Tutelyan V.A., Nikityuk D.B. The global challenge of the XXI century – COVID-19: the answer of dietetics. Voprosy pitaniia [Problems of Nutrition]. 2021; 90 (5): 6–14. DOI: https://doi.org/10.33029/0042-8833-2021-90-5-6-14 (in Russian)

59. Aguila E.J.T., Cua I.H.Y., Fontanilla J.A.C., Yabut V.L.M., Causing M.F.P. Gastrointestinal manifestations of COVID-19: impact on nutrition practices. Nutr Clin Pract. 2020; 35 (5): 800–5. DOI: https://doi.org/10.1002/ncp.10554

60. Martindale A., Patel J.J., Taylor B., Warren M., McClave S.A. American Society for Parenteral and Enteral Nutrition (ASPEN) nutrition therapy in the patient with COVID‐19 disease requiring ICU care. URL: https://www.nutritioncare.org/Guidelines_and_Clinical_Resources/Resources_for_Clinicians_Caring_for_Patients_with_Coronavirus/ (date of access July 07, 2021)

61. Oba J., Carvalho W.B., Silva C.A., Delgado A.F. Gastrointestinal manifestations and nutritional therapy during COVID-19 pandemic: a practical guide for pediatricians. Einstein (Sao Paulo, Brazil). 2020; 18: eRW5774. DOI: https://doi.org/10.31744/einstein_journal/2020rw5774

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