Consequences of COVID-19: prevalence and approaches to Long-COVID symptoms therapy


DOI: https://dx.doi.org/10.18565/therapy.2021.10.148-159

Malyavin A.G.

A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of Russia
Abstract. Article reviews current international data on the pathogenesis and prevalence of Long-COVID symptoms. According to the results of All-Russian survey of physicians organized by Russian Scientific Medical Society of Internal Medicine (RSMSIM), it was shown that neurological, pulmonological and gastroenterological symptoms are found in most COVID-19 convalescents during appointments to doctors of various specialties. The aim of the review is to provide a description of possible approaches to pharmacotherapy of post-COVID symptoms in accordance with the frequency of Long-COVID symptoms occurrence in patients in Russian clinical practice.
Keywords: Long-COVID, functional gastrointestinal disorders, psycho-emotional disorders, asthenia, cognitive disorders
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Literature


  1. International Statistical Classification of Diseases and Related Health Problems 10th Revision. Available at: https://icd.who.int/browse10/2019/en#/ (date of access – 01.12.2021).

  2. Cabrera Martimbianco A.L., Pacheco R.L., Bagattini A.M., Riera R. Frequency, signs and symptoms, and criteria adopted for long COVID: a systematic review. Int J Clin Pract. 2021; 75(10): e14357. doi: 10.1111/ijcp.14357.

  3. COVID-19 rapid guideline: managing the long-term effects of COVID-19. London: National Institute for Health and Care Excellence (UK); 2020 Dec 18. PMID: 33555768 Bookshelf ID: NBK567261.

  4. Воробьева О.В. Комплексная терапия последствий коронавирусной инфекции COVID-19. Доктор.Ру. 2021; 5: 13–19. [Vorobieva O.V. Combined therapy of COVID-19 infection consequences. Doctor.Ru. 2021; 5: 13–19 (In Russ.)]. https://dx.doi.org/10.31550/1727-2378-2021-20-5-13-19.

  5. Alabdali A.Y.M., Chinnappan S., Abd Razik B.M. et al. Impact of covid-19 on multiple body organ failure: A review. Indian J Forensic Med Toxicol. 2021; 5(4): 835–44.

  6. Li Z., Liu T., Yang N. et al. Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain. Front Med. 2020; 14(5): 533–41. doi: 10.1007/s11684-020-0786-5.

  7. Wenting A., Gruters A., van Os Y. et al. COVID-19 neurological manifestations and underlying mechanisms: A scoping review. Front Psychiatry. 2020; 11: 860. doi: 10.3389/fpsyt.2020.00860.

  8. Boldrini M., Canoll P.D., Klein R.S. How COVID-19 affects the brain. JAMA Psychiatry. 2021; 78(6): 682–83. doi: 10.1001/jamapsychiatry.2021.0500.

  9. Rudroff T., Fietsam A.C., Deters J.R. et al. Post-covid-19 fatigue: Potential contributing factors. Brain Sci. 2020; 10(12): 1012. doi: 10.3390/brainsci10121012.

  10. Оstergaard L. SARS CoV2 related microvascular damage and symptoms during and after COVID19: Consequences of capillary time changes, tissue hypoxia and inflammation. Physiol Rep. 2021; 9(3): e14726. doi: 10.14814/phy2.14726.

  11. Cardinale V., Capurso G., Ianiro G. Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis. Dig Liver Dis. 2020; 52(12): 1383–89. doi: 10.1016/j.dld.2020.09.009.

  12. Mitsuyama K., Tsuruta K., Takedatsu H. et al. Clinical features and pathogenic mechanisms of gastrointestinal injury in COVID-19. J Clin Med. 2020; 9(11): 3630. doi: 10.3390/jcm9113630.

  13. Yeoh Y.K., Zuo T., Lui G.C. et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021; 70(4): 698–706. doi: 10.1136/gutjnl-2020-323020.

  14. Barbara G., Grover M., Bercik P. et al. Rome foundation working team report on post-infection irritable bowel syndrome. Gastroenterology. 2019; 156(1): 46–58. e7. doi: 10.1053/j.gastro.2018.07.011.

  15. Reznikov L.R., Norris M.H., Vashisht R. et al. Identification of antiviral antihistamines for COVID-19 repurposing. Biochem Biophys Res Commun. 2021; 538: 173–79. doi: 10.1016/j.bbrc.2020.11.095.

  16. Hogan Ii R.B., Hogan Iii R.B., Cannon T. et al. Dual-histamine receptor blockade with cetirizine – famotidine reduces pulmonary symptoms in COVID-19 patients. Pulm Pharmacol Ther. 2020; 63: 101942. doi: 10.1016/j.pupt.2020.101942.

  17. Carfì A., Bernabei R., Landi F.; Gemelli against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA. 2020; 324(6): 603–05. doi: 10.1001/jama.2020.12603.

  18. Galvan-Tejada C.E., Herrera-Garcia C.F., Godina-Gonzalez S. et al. Persistence of COVID-19 symptoms after recovery in Mexican population. Int J Environ Res Public Health. 2020; 17(24): 9367. doi: 10.3390/ijerph17249367.

  19. Goertz Y.M.J., Van Herck M., Delbressine J.M. et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020; 6(4): 00542-2020. doi: 10.1183/23120541.00542-2020.

  20. Jennings G., Monaghan A., Xue F. et al. A systematic review of persistent symptoms and residual abnormal functioning following acute COVID-19: Ongoing symptomatic phase vs. post-COVID-19 syndrome. medRxiv. 2021. doi: 10.1101/2021.06.25.21259372.

  21. Frontera J.A., Yang D., Lewis A. et al. A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications. J Neurol Sci. 2021; 426: 117486. doi: 10.1016/j.jns.2021.117486.

  22. Seeble J., Waterboer T., Hippchen T. et al. Persistent symptoms in adult patients 1 year after coronavirus disease 2019 (COVID-19): A prospective cohort study. Clin Infect Dis. 2021: ciab611. doi: 10.1093/cid/ciab611. Online ahead of print.

  23. Raveendran A.V., Jayadevan R., Sashidharan S. Long COVID: An overview. Diabetes Metab Syndr. 2021; 15(3): 869–75. doi: 10.1016/j.dsx.2021.04.007.

  24. Poyraz B.C., Poyraz C.A., Olgun Y. Psychiatric morbidity and protracted symptoms after COVID. Psychiatry Res. 2021; 295: 113604. doi: 10.1016/j.psychres.2020.113604.

  25. Carvalho-Schneider C., Laurent E., Lemaignen A. et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect. 2021; 27(2): 258–63. doi: 10.1016/j.cmi.2020.09.052.

  26. Blackett J.W., Li J., Jodorkovsky D., Freedberg D.E. Prevalence and risk factors for gastrointestinal symptoms after recovery from COVID-19. Neurogastroenterol Motil. 2021: e14251. doi: 10.1111/nmo.14251. Online ahead of print.

  27. Wankowicz P., Szylinska A., Rotter I. The impact of the COVID-19 pandemic on psychological health and insomnia among people with chronic diseases. J Clin Med. 2021; 10(6): 1206. doi: 10.3390/jcm10061206.

  28. Fernandez-de-Las-Penas C., Torres-Macho J., Velasco-Arribas M. et al. Similar prevalence of long-term post-COVID symptoms in patients with asthma: A case-control study. J Infect. 2021; 83(2): 237–79. doi: 10.1016/j.jinf.2021.04.034.

  29. Malik P., Patel K., Pinto C. et al. Post-acute COVID-19 syndrome and health-related quality of life – a systematic review and meta-analysis. J Med Virol. 2021; 94(1): 253–62. doi: 10.1002/jmv.27309.

  30. Liu K., Zhang W., Yang Y. et al. Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study. Complement Ther Clin Pract. 2020; 39: 101166. doi: 10.1016/j.ctcp.2020.101166.

  31. Available at: https://app.magicapp.org/#/guideline/EQpzKn/section/L6qOzj (date of access – 01.12.2021).

  32. Wainwright T.W., Low M. Beyond acute care: Why collaborative self-management should be an essential part of rehabilitation pathways for COVID-19 patients. J Rehabil Med. 2020; 52(5): jrm00055. doi: 10.2340/16501977-2685.

  33. Clinicaltrials.gov U.S. National Library of Medicine. Available at: https://clinicaltrials.gov (date of access – 01.12.2021).

  34. Временные методические рекомендации. Медицинская реабилитация при новой коронавирусной инфекции COVID-19. Версия 2 (31.07.2020). Минздрав России. Доступ: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/051/187/original/31072020_Reab_COVID-19_v1.pdf (дата обращения – 01.12.2021). [Temporary guidelines. Medical rehabilitation for the new coronavirus infection COVID-19. Version 2 (31.07.2020). Ministry of Healthcare of Russia. Available at: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/051/187/original/31072020_Reab_COVID-19_v1.pdf (date of access – 01.12.2021) (In Russ.)].

  35. Малявин А.Г, Адашева Т.В., Бабак С.Л. с соавт. Медицинская реабилитация больных, перенесших COVID-19-инфекцию. Методические рекомендации. Терапия. 2020; S5: 1–48. [Malyavin A.G., Adasheva T.V., Babak S.L. et al. Medical rehabilitation of COVID-19-survived patients. Methodological recommendations. Terapiya = Therapy. 2020; S5: 1–48 (In Russ.)]. https://dx.doi.org/10.18565/therapy.2020.5suppl.1–48.

  36. Mura C., Preissner S., Nahles S. et al. Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients. Signal Transduct Target Ther. 2021; 6(1): 267. doi: 10.1038/s41392-021-00689-y.

  37. Weinstock L.B., Brook J.B., Walters A.S. et al. Mast cell activation symptoms are prevalent in Long-COVID. Int J Infect Dis. 2021; 112: 217–26. doi: 10.1016/j.ijid.2021.09.043.

  38. Afrin L.B., Weinstock L.B., Molderings G.J. Covid-19 hyperinflammation and post-Covid19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020; 100: 327–32. doi: 10.1016/j.ijid.2020.09.016.

  39. Lam H.Y., Tergaonkar V., Kumar A.P., Ahn K.S. Mast cells: Therapeutic targets for COVID-19 and beyond. IUBMB Life. 2021; 73(11): 1278–92. doi: 10.1002/iub.2552.

  40. Kazama I. Stabilizing mast cells by commonly used drugs: a novel therapeutic target to relieve post-COVID syndrome? Drug Discov Ther. 2020; 14(5): 259–61. doi: 10.5582/ddt.2020.03095.

  41. Гущин И.С., Крышень К.Л., Бондаренко А.Б. Противовоспалительная активность противоаллергического препарата теоритина. Российский аллергологический журнал. 2021; 2: 20–31. [Gushchin I.S., Kryshen K.L., Bondarenko A.B. Anti-inflammatory activity of the antiallergic drug 7-[4-(4-benzhydrylpiperazinyl-1)butyl]-3-methylxanthine succinate (Theoritin). Rossiyskiy allergologicheskiy zhurnal = Russian Journal of Allergy. 2021; 2: 20–31 (In Russ.)]. https://dx.doi.org/10.36691/RJA1445.

  42. РКИ № 26 (23.01.2017). Многоцентровое, открытое, рандомизированное, сравнительное исследование по оценке эффективности и безопасности препарата Теоритин®, таблетки 2 мг, производства ЗАО «Обнинская химико-фармацевтическая компания», Россия, в сравнении с препаратом Эриус®, таблетки, покрытые пленочной оболочкой 5 мг, производства Шеринг Плау Лабо Н.В., Бельгия, при лечении взрослых пациентов с хронической идиопатической крапивницей. Доступ: https://grls.rosminzdrav.ru/ (дата обращения – 01.12.2021). [RCI No. 26 (23.01.2017). Multicenter, open-label, randomized, comparative study to assess the efficacy and safety of Theoritin®, 2 mg tablets, manufactured by Obninsk Chemical-Pharmaceutical Company, Russia, in comparison with Erius®, 5 mg film-coated tablets, manufactured by Schering Plow Labo N.V., Belgium, in the treatment of adult patients with chronic idiopathic urticaria. Available at: https://grls.rosminzdrav.ru/ (date of access – 01.12.2021) (In Russ.)].

  43. РКИ № 270 (05.06.2018). Многоцентровое, открытое, рандомизированное, сравнительное исследование по оценке эффективности и безопасности препарата Теоритин®, таблетки 4 мг, производства ЗАО «Обнинская химико-фармацевтическая компания», Россия, в сравнении с препаратом Эриус®, таблетки, покрытые пленочной оболочкой 5 мг, производства Шеринг Плау Лабо Н.В., Бельгия, у взрослых пациентов с сезонным аллергическим ринитом. Доступ: https://grls.rosminzdrav.ru/ (дата обращения – 01.12.2021). [RCI No. 270 (05.06.2018). Multicenter, open, randomized, comparative study to assess the efficacy and safety of the drug Theoritin®, 4 mg tablets, manufactured by Obninsk Chemical-Pharmaceutical Company, Russia, in comparison with Erius®, film-coated tablets 5 mg, produced by Schering Plow Labo N.V., Belgium, in adult patients with seasonal allergic rhinitis. Available at: https://grls.rosminzdrav.ru/ (date of access – 01.12.2021) (In Russ.)].

  44. Weston M.C., Peachell P.T. Regulation of human mast cell and basophil function by cAMP. Gen Pharmacol. 1998; 31(5): 715–19. doi: 10.1016/s0306-3623(98)00080-9.

  45. Finn D.F., Walsh J.J. Twenty-first century mast cell stabilizers. Br J Pharmacol. 2013; 170(1): 23–37. doi: 10.1111/bph.12138.

  46. Bhat J.A., Gupta S., Kumar M. Neuroprotective effects of theobromine in transient global cerebral ischemia-reperfusion rat model. Biochem Biophys Res Commun. 2021; 571: 74–80. doi: 10.1016/j.bbrc.2021.07.051.

  47. Seirafianpour F., Mozafarpoor S., Fattahiet N. al. Treatment of COVID-19 with pentoxifylline: Could it be a potential adjuvant therapy? Dermatol Ther. 2020; 33(4): e13733. doi: 10.1111/dth.13733.

  48. Инструкция по медицинскому применению препарата Нанотропил® Ново. РУ: ЛП-004616. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.rosminzdrav.ru/ (дата обращения – 01.12.2021). [Instructions for the medical use of the medicinal product Nanotropil® Novo. Registration certificate: ЛП-004616. State Register of Medicines of the Ministry of Health of Russia. Available at: https://grls.rosminzdrav.ru/ (date of access – 01.12.2021) (In Russ.)].

  49. Ковалев Г.И., Ахапкина В.И., Абаимов Д.А., Фирстова Ю.Ю. Фенотропил как рецепторный модулятор синаптической нейропередачи. Атмосфера. Нервные болезни. 2007; 4: 22–26. [Kovalev G.I., Akhapkina V.I., Abaimov D.A., Firstova Yu.Yu. Phenotropil as a receptor modulator of synaptic neurotransmission. Atmosfera. Nervnyye bolezni = Atmosphere. Nervous Diseases. 2007; 4: 22–26 (In Russ.)].

  50. Zvejniece L., Svalbe B., Vavers E. et al. S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity. Pharmacol Biochem Behav. 2017; 160: 21–29. doi: 10.1016/j.pbb.2017.07.009.

  51. Vaarmann A., Kovac S., Holmstrom K.M. et al. Dopamine protects neurons against glutamate-induced excitotoxicity. Cell Death Dis. 2013; 4(1): e455. doi: 10.1038/cddis.2012.194.

  52. Федин А.И., Амчеславская Е.В., Красноперов Е.Н., Белопасова А.В. Применение Фенотропила у больных с хронической ишемией мозга и умеренными когнитивными нарушениями. Нервные болезни. 2010; 3: 22–31. [Fedin A.I., Amcheslavskaya E.V., Krasnoperov E.N., Belopasova A.V. The use of Phenotropil in patients with chronic cerebral ischemia and moderate cognitive impairment. Nervnyye bolezni = Nervous Diseases. 2010; 3: 22–31 (In Russ.)].

  53. Кадыков А.С., Шахпаронова Н.В., Кашина Е.М. Астенические состояния в клинике сосудистых заболеваний головного мозга и возможности их коррекции. Нервные болезни. 2012; 1: 24–28. [Kadykov A.S., Shakhparonova N.V., Kashina E.M. Asthenic conditions in the clinic of vascular diseases of the brain and the possibility of their correction. Nervnyye bolezni = Nervous Diseases. 2012; 1: 24–28 (In Russ.)].

  54. Новикова Л.Б. Влияние Фенотропила на качество жизни больных с цереброваскулярной патологией. Атмосфера. Нервные болезни. 2008; 1: 18–21. [Novikova L.B. Effect of Phenotropil on the quality of life of patients with cerebrovascular pathology. Atmosfera. Nervnyye bolezni = Atmosphere. Nervous Diseases. 2008; 1: 18–21 (In Russ.)].

  55. Ellul M.A., Benjamin L., Singh B. et al Neurological associations of COVID-19. Lancet Neurol. 2020; 19(9): 767–83. doi: 10.1016/S1474-4422(20)30221-0.

  56. Кукес В.Г., Парфенова О.К., Сидоров Н.Г. с соавт. Окислительный стресс и воспаление в патогенезе COVID. РМЖ. 2020; 4: 244–247. [Kukes V.G., Parfenova O.K., Sidorov N.G. et al. Oxidative stress and inflammation in COVID-19 pathogenesis. Rossiyskiy meditsinskiy zhurnal = Russian Medical Journal. 2020; 4: 244–247 (In Russ.)]. https://dx.doi.org/10.17816/0869-2106-2020-26-4-244-247.

  57. Инструкция по медицинскому применению препарата Этоксидол®. РУ: ЛП-002227. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.rosminzdrav.ru/ (дата обращения – 01.12.2021). [Instructions for the medical use of the medicinal product Ethoxidol®. Registration certificate: ЛП-002227. State Register of Medicines of the Ministry of Health of Russia. Available at: https://grls.rosminzdrav.ru/ (date of access – 01.12.2021) (In Russ.)].

  58. И.В. Кукес, Ж.М. Салмаси, К.С. Терновой с соавт. Предпосылки к созданию атласа постковидного воспаления как способа персонализированной фармакотерапии, а также прогнозирования и предупреждения органных и системных дисфункций. Медицинский совет. 2021; 12: 72–88. [Kukes I.V., Salmasi J.M., Ternovoy K.S. et al. Prerequisites for the creation of an atlas of postcovid inflammation as a way of personalized pharmacotherapy, as well as predicting and preventing organ and systemic dysfunctions. Meditsinskiy sovet = Medical Council. 2021; 12: 72–88 (In Russ.)]. https://dx.doi.org/10.21518/2079-701X-2021-12-72-88.

  59. Боголепова А.Н., Коваленко Е.А., Махнович Е.В., Осиновская Н.А. Оценка эффективности применения препарата Этоксидол у пациентов с хронической ишемией мозга. Журнал неврологии и психиатрии им. C.C. Корсакова. 2021; 9: 31–37. [Bogolepova A.N., Kovalenko E.A., Makhnovich E.V., Osinovskaya N.A. The assessment of the efficacy of Ethoxidol treatment in patients with chronic cerebral ischemia. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = Journal of Neurology and Psychiatry named after S.S. Korsakov. 2021; 9: 31–37 (In Russ.)]. https://dx.doi.org/10.17116/jnevro202112109131.

  60. Итоги исследования отечественного препарата, антиоксиданта II поколения – Этоксидола. Под ред. Арчакова А.И., Кукеса В.Г., Дмитриева Д.А. М.: МАКФиФ. 2014; 90 с. [Results of a study of a domestic drug, an antioxidant of the second generation – Ethoxidol. Ed. by Archakov A.I., Kukes V.G., Dmitriev D.A. Moscow: MAKFiF. 2014; 90 pp. (In Russ.)].

  61. Кукес В.Г., Парфенова О.К., Романов Б.К. с соавт. Механизм действия Этоксидола на показатели окислительного стресса при сердечной недостаточности и гипертонии. Современные технологии в медицине. 2020; 2: 67–73. [Kukes V.G., Parfenova O.K., Romanov B.K. et al. The mechanism of action of Ethoxidol on oxidative stress indices in heart failure and hypotension. Sovremennyye tekhnologii v meditsine = Modern Technologies in Medicine. 2020; 2: 67–73 (In Russ.)]. https://dx.doi.org/10.17691/stm2020.12.2.08.

  62. Инструкция по медицинскому применению препарата Тералиджен®. РУ: ЛП-000642. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.rosminzdrav.ru/ (дата обращения – 01.12.2021). [Instructions for the medical use of the medicinal product Teralygen®. Registration certificate: ЛП-000642. State Register of Medicines of the Ministry of Health of Russia. Available at: https://grls.rosminzdrav.ru/ (date of access – 01.12.2021) (In Russ.)].

  63. Аведисова А.С. (под редакцией), Шаповалов Д.Л. (составитель). Применение нейролептика Алимемазина (Тералиджен) в лечении психических расстройств. Информационно-методические материалы. Воронеж. 2017; 1–18. [A.S. Avedisova (edited by), D.L. Shapovalov (compiler). The use of the neuroleptic Alimemazine (Teraligen) in the treatment of mental disorders. Information and methodological materials. Voronezh. 2017; 1–18 (In Russ.)].

  64. Беккер Р.А., Быков Ю.В. Алимемазин: обзор применения. Психиатрия и психофармакотерапия. 2016; 6: 10–20. [Bekker R.A., Bykov Yu.V. Alimemazine: a review. Psikhiatriya i psikhofarmakoterapiya = Psychiatry and psychopharmacotherapy. 2016; 6: 10–20 (In Russ.)].

  65. Сиволап Ю.П. Систематика и лечение тревожных расстройств. Журнал неврологии и психиатрии им. С.С. Корсакова. 2020; 7: 121–127. [Sivolap Yu.P. Systematics and treatment of anxiety disorders. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = Journal of Neurology and Psychiatry named after S.S. Korsakov. 2020; 7: 121–127 (In Russ.)]. https://dx.doi.org/10.17116/jnevro2020120071121.

  66. Бухтояров О.В., Самарин Д.М. Антилетальная терапия COVID-19 для амбулаторного лечения в домашних условиях. European Journal of Medical and Health Sciences. 2021; 4: 1–8. [Bukhtoyarov O.V., Samarin D.M. Anti-lethal COVID-19 therapy for outpatient home care. European Journal of Medical and Health Sciences. 2021; 4: 1–8 (In Russ.)]. https://dx.doi.org/10.24018/ejmed.2021.3.4.960.

  67. Yang L., Pei R.J., Li H. et al. Identification of SARS-CoV-2 entry inhibitors among already approved drugs. Acta Pharmacol Sin. 2020; 42(8): 1347–53. doi: 10.1038/s41401-020-00556-6.

  68. Бухтояров О.В., Самарин Д.М. Опыт сочетанного применения Ронколейкина и Виферона в лечении больных COVID-19. Терапевт. 2021; 2: 57–69. [Bukhtoyarov O.V., Samarin D.M. The experience of the combined use of Roncoleukin® and Viferon® in the treatment of patients with COVID-19. Terapevt = Therapist. 2021; 2: 57–69 (In Russ.)]. https://dx.doi.org/10.33920/MED-12-2102-07.

  69. Инструкция по медицинскому применению препарата Гипоксен®. РУ: Р N001939/02. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.rosminzdrav.ru/ (дата обращения – 01.12.2021). [Instructions for the medical use of the medicinal product Hypoxene®. Registration certificate: Р N001939/02. State Register of Medicines of the Ministry of Health of Russia. Available at: https://grls.rosminzdrav.ru/ (date of access – 01.12.2021) (In Russ.)].

  70. Смирнов В.С., Кузьмич М.К. Гипоксен. СПБ: ФАРМиндекс. 2001; 67 с. [Smirnov V.S., Kuzmich M.K. Hypoxene. Saint Petrsburg: PHARMindex. 2001; 67 pp. (In Russ.)].

  71. Игнатьев В.А., Петрова И.В., Цветкова Л.Н. Опыт применения Гипоксена (олифена) в лечении пациентов с хронической обструктивной болезнью легких среднетяжелого и тяжелого течения. Terra medica. 2010; 3: 19–24. [Ignatiev V.A., Petrova I.V., Tsvetkova L.N. Experience of using Hypoxen (olifen) in the treatment of patients with moderate and severe chronic obstructive pulmonary disease. Terra medica. 2010; 3: 19–24 (In Russ.)].

  72. Горошко О.А., Кукес В.Г., Прокофьев А.Б. с соавт. Клинико-фармакологические аспекты применения антиоксидантных лекарственных средств. Международный журнал прикладных и фундаментальных исследований. 2016; 4–5: 905–912. [Goroshko O.A., Kukes V.G., Prokofiev A.B. et al. Clinico-pharmacological aspects of application of antioxidant drugs. Mezhdunarodnyy zhurnal prikladnykh i fundamental’nykh issledovaniy = International Journal of Applied and Basic Research. 2016; 4–5: 905–912 (In Russ.)].

  73. Инструкция по медицинскому применению лекарственного препарата Тримедат®. РУ: ЛП-002527. Государственный реестр лекарственных средств Минздрава России. Доступ: https://grls.rosminzdrav.ru/ (дата обращения – 01.12.2021). [Instructions for the medical use of the medicinal product Trimedat®. Registration certificate: ЛП-002527. State Register of Medicines of the Ministry of Health of Russia. Available at: https://grls.rosminzdrav.ru/ (date of access – 01.12.2021) (In Russ.)].

  74. Ruepert L., Quartero A.O., de Wit N.J. et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011; 8: CD003460. doi: 10.1002/14651858.CD003460.pub3.

  75. Yang Y.J., Bang C.S., Baik G.H. et al. Prokinetics for the treatment of functional dyspepsia: Bayesian network meta-analysis. BMC Gastroenterol. 2017; 17(1): 83. doi: 10.1186/s12876-017-0639-0.

  76. Андреев Д.Н., Маев И.В. Эффективность тримебутина в рамках лечения функциональных заболеваний ЖКТ и желчных путей: наблюдательное многоцентровое исследование. Терапевтический архив. 2021; 8: 897–903. [Andreev D.N., Maev I.V. Efficacy of trimebutine in the treatment of functional gastrointestinal disorders: an observational multicenter study. Terapevticheskiy arkhiv = Therapeutic Archive. 2021; 8: 897–903 (In Russ.)]. https://dx.doi.org/10.26442/00403660.2021.08.200919.

  77. Кардашева С.С., Картавенко И.М., Максимова Н.Б. с соавт. Эффективность тримебутина малеата в лечении пациентов с функциональной диспепсией: результаты наблюдательного исследования TREND. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2018; 5: 67–76. [Kardasheva S.S., Kartavenko I.M., Maksimova N.B. et al. Efficacy of trimebutine maleate (Trimedat®) in the treatment of patients with functional dyspepsia: results of the TREND observational study. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018; 5: 67–76 (In Russ.)]. https://dx.doi.org/10.22416/1382-4376-2018-28-5-67-76.

  78. Rahman M.Z., Ahmed D.S., Mahmuduzzaman M. et al. Comparative efficacy and safety of trimebutine versus mebeverine in the treatment of irritable bowel syndrome. Mymensingh Med J. 2014; 23(1): 105–13.

  79. Ogawa N., Nakajima S., Tamada K. et al. Trimebutine suppresses Toll-like receptor 2/4/7/8/9 signaling pathways in macrophages. Arch Biochem Biophys. 2021; 711: 109029. doi: 10.1016/j.abb.2021.109029.

  80. Poynard T., Regimbeau C., Benhamou Y. Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2001; 15(3): 355–61. doi: 10.1046/j.1365-2036.2001.00937.x.

  81. Ivashkin V., Drapkina O.M., Poluektova E.A. et al. The effect of a multistrain probiotic on the symptoms and small intestinal bacterial overgrowth in constipation-predominant irritable bowel syndrome: A randomized, simple-blind, placebo-controlled trial. Am J Clin Med Res. 2015; 3(2): 18–23. doi: 10.12691/ajcmr-3-2-1.

  82. Типикина М.Ю. Оценка роли воспалительных и микробиологических изменений при синдроме раздраженного кишечника у детей. Диссертация. 2014. Санкт-Петербургский государственный педиатрический медицинский университет. [Tipikina M.Yu. Assessment of the role of inflammatory and microbiological changes in irritable bowel syndrome in children. Thesis. 2014. Saint Petersburg State Pediatric Medical University (In Russ.)].


About the Autors

Andrei G. Malyavin, MD, professor, professor of the Department of phthisiology and pulmonology of the faculty of general medicine, A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of Russia. Address: 107150, Moscow, 39/2 Losinoostrovskaya Str. E-mail: maliavin@mail.ru. ORCID: 0000-0002-6128-5914


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