Effect of systemic ozone therapy added to pharmacological treatment on brain-derived neurotrophic factor (BDNF) and cognitive status in post-COVID patients

Abstract

BACKGROUND: Treatment is required for post-COVID cognitive impairment associated with functional limitations, reduced work capacity, and significant deterioration in quality of life. Pharmacological treatment is ineffective. In this context, physical therapy, especially systemic ozone therapy with potential neuroprotective effects, appears promising.

AIM: The aim of the study was to evaluate the effect of systemic ozone therapy added to pharmacological treatment on plasma brain-derived neurotrophic factor (BDNF) levels and cognitive status in patients with post-COVID cognitive impairment.

MATERIALS AND METHODS: A total of 140 patients aged 18-45 years with post-COVID asthenic syndrome were evaluated and treated. They were randomized into two groups: an experimental group with 70 subjects who received systemic ozone therapy in addition to pharmacological treatment and the comparator group with 70 subjects who received pharmacological treatment only. Pre- and post-treatment outcomes were assessed using plasma BDNF levels and the Montreal Cognitive Assessment (MoCa) score.

RESULTS: Statistically significant differences in BDNF levels (р=0.034) and MoCa scores (р=0.002) were found between the compared groups at the end of therapy (day 30). In our study, adding systemic ozone therapy to pharmacological treatment in patients with post-COVID cognitive impairment normalized BDNF levels and completely improved clinical manifestations of cognitive impairment in 95% of subjects.

CONCLUSION: Therefore, systemic ozone therapy can be considered as one of the effective and pathogenetically proven strategies for comprehensive treatment of patients with post-COVID cognitive impairment in the outpatient setting.

Keywords

post-COVID cognitive impairment / systemic ozone therapy / brain-derived neurotrophic factor / BDNF

References

[1] Buttery S, Philip KE, Williams P, et al. Patient symptoms and experience following COVID-19: Results from a UK-wide survey. BMJ Open Respir Res. 2021;8(1):e001075. doi: 10.1136/bmjresp-2021-001075

[2] Buttery S., Philip K.E., Williams P., et al. Patient symptoms and experience following COVID-19: Results from a UK-wide survey // BMJ Open Respir Res. 2021. Vol. 8, N 1. P. e001075. doi: 10.1136/bmjresp-2021-001075

[3] Chen C, Haupert SR, Zimmermann L, et al. Global prevalence of post COVID-19 condition or long COVID: A meta-analysis and systematic review. J Infect Dis. 2022;226(9):1593–1607. doi: 10.1093/infdis/jiac136

[4] Chen C., Haupert S.R., Zimmermann L., et al. Global prevalence of post COVID-19 condition or long COVID: A meta-analysis and systematic review // J Infect Dis. 2022. Vol. 226, N 9. P. 1593–1607. doi: 10.1093/infdis/jiac136

[5] Seang S, Itani O, Monsel G, et al. Long COVID-19 symptoms: Clinical characteristics andrecovery rate among non-severe outpatients over a six-month follow-up. Infect Dis Now. 2022; 52(3):165–169. EDN: VYRYWF doi: 10.1016/j.idnow.2022.02.005

[6] Seang S., Itani O., Monsel G., et al. Long COVID-19 symptoms: Clinical characteristics andrecovery rate among non-severe outpatients over a six-month follow-up // Infect Dis Now. 2022. Vol. 52, N 3. P. 165–169. EDN: VYRYWF doi: 10.1016/j.idnow.2022.02.005

[7] Davis HE, Assaf GS, McCorkell L, et al. Characterizing long COVID in an international cohort: 7 Months of symptoms and their impact. EClinicalMedicine. 2021;38:101019. doi: 10.1016/j.eclinm.2021.101019

[8] Davis H.E., Assaf G.S., McCorkell L., et al. Characterizing long COVID in an international cohort: 7 Months of symptoms and their impact // EClinicalMedicine. 2021. Vol. 38. P. 101019. doi: 10.1016/j.eclinm.2021.101019

[9] Boutou AK, Asimakos A, Kortianou E, et al. Long COVID-19 pulmonary sequelae and management considerations. J Personal. Med. 2021;11(9):838. doi: 10.3390/jpm11090838

[10] Boutou A.K., Asimakos A., Kortianou E., et al. Long COVID-19 pulmonary sequelae and management considerations // J Personal. Med. 2021. Vol. 11, N 9. P. 838. doi: 10.3390/jpm11090838

[11] Zaharov DV, Burjak JV. Postcognitive cognitive disorders. Current view of the problem, pathogenesis and therapy. Obozrenie psihiatrii i medicinskoj psihologii imeni V.M. Behtereva = Bekhterev review of psychiarty and medical psychology. 2021;55(4):97–105. EDN: QSADXH. doi: 10.31363/2313-7053-2021-57-4-97-105

[12] Захаров Д.В., Буряк Ю.В. Постковидные когнитивные расстройства. Современный взгляд на проблему, патогенез и терапию // Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева. 2021. Т. 55, № 4. С. 97–105. EDN: QSADXH. doi: 10.31363/2313-7053-2021-57-4-97-105

[13] Hasanova DR, Zhitkova JV, Vaskaeva GR. Post-COVID syndrome: A review of pathophysiology, neuropsychiatrie manifestations and treatment perspectives. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, neuropsychiatry, psychosomatics. 2021;13(3):93–98. EDN: YJESZP doi: 10.14412/2074-2711-2021-3-93-98

[14] Хасанова Д.Р., Житкова Ю.В., Васкаева Г.Р. Постковидный синдром: обзор знаний о патогенезе, нейропсихиатрических проявлениях и перспективах лечения // Неврология, нейропсихиатрия, психосоматика. 2021. Т. 13, № 3. С. 93–98. EDN: YJESZP doi: 10.14412/2074-2711-2021-3-93-98

[15] Ahmedzhanova LT, Ostroumova TM, Soloha OA. Management of patients with pain syndromes associated with Covid-19. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, neuropsychiatry, psychosomatics. 2021;13(5):96–101. EDN: MAFHCH doi: 10.14412/2074-2711-2021-5-96-101

[16] Ахмеджанова Л.Т., Остроумова Т.М., Солоха О.А. Ведение пациентов с болевыми синдромами на фоне COVID-19 // Неврология, нейропсихиатрия, психосоматика. 2021. Т. 13, № 5. С. 96–101. EDN: MAFHCH doi: 10.14412/2074-2711-2021-5-96-101

[17] Hajbullina DH, Maksimov JN. Asthenic post-covid syndrome. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov J Neurol Psychiatry. 2023;23(3):61–69. EDN: XQXTAI doi: 10.17116/jnevro202312303161

[18] Хайбуллина Д.Х., Максимов Ю.Н. Астенический постковидный синдром // Журнал неврологии и психиатрии им. С.С. Корсакова. 2023. Т. 123, № 3. С. 61–69. EDN: XQXTAI doi: 10.17116/jnevro202312303161

[19] Naumov KM, Andreeva GO, Bazhenov DA. Differentiated approach to the correction of autonomic disorders in long COVID-19. Russ Military Med Acad Reports. 2021;40(S4):88–91. EDN: PUNVWN

[20] Наумов К.М., Андреева Г.О., Баженов Д.А. Дифференцированный подход к коррекции вегетативных нарушений при постковидном синдроме // Известия Российской Военно-медицинской академии. 2021. Т. 40, № S4. С. 88–91. EDN: PUNVWN

[21] Razumov AN, Ponomarenko GN, Badtieva VA, et al. Medical rehabilitation of patients who have suffered COVID-19 in sanatorium-resort organizations. Methodological recommendations. Saint Petersburg; 2021. 30 p. (In Russ.) EDN: AEDCML

[22] Разумов А.Н., Пономаренко Г.Н., Бадтиева В.А., и др. Медицинская реабилитация пациентов, перенесших COVID-19, в санаторно-курортных организациях. Методические рекомендации. Санкт-Петербург, 2021. 30 с. EDN: AEDCML

[23] Georgieva E, Ananiev J, Yovchev Y, et al. COVID-19 complications: Oxidative stress, inflammation, and mitochondrial and endothelial dysfunction. Int J Mol Sci. 2023;24(19):14876. EDN: BYFCQR doi: 10.3390/ijms241914876

[24] Georgieva E., Ananiev J., Yovchev Y., et al. COVID-19 complications: Oxidative stress, inflammation, and mitochondrial and endothelial dysfunction // Int J Mol Sci. 2023. Vol. 24, N 19. P. 14876. EDN: BYFCQR doi: 10.3390/ijms241914876

[25] Scassellati C, Galoforo AC, Bonvicini C, et al. Ozone: A natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders. Ageing Res Rev. 2020;63:101138. EDN: HVHVTG doi: 10.1016/j.arr.2020.101138

[26] Scassellati C., Galoforo A.C., Bonvicini C., et al. Ozone: A natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders // Ageing Res Rev. 2020. Vol. 63. P. 101138. EDN: HVHVTG doi: 10.1016/j.arr.2020.101138

[27] Frosini M, Contartese A, Zanardi I, et al. Selective ozone concentrations may reduce the ischemic damage after a stroke. Free Radic. Res. 2012;46:612–618. doi: 10.3109/10715762.2012.659247

[28] Frosini M., Contartese A., Zanardi I., et al. Selective ozone concentrations may reduce the ischemic damage after a stroke // Free Radic. Res. 2012. Vol. 46. P. 612–618. doi: 10.3109/10715762.2012.659247

[29] Scassellati C, Ciani M, Galoforo AC, et al. Molecular mechanisms in cognitive frailty: Potential therapeutic targets for oxygen-ozone treatment. Mech Ageing Dev. 2020;186:111210. EDN: BIDSKP doi: 10.1016/j.mad.2020.111210

[30] Scassellati C., Ciani M., Galoforo A.C., et al. Molecular mechanisms in cognitive frailty: Potential therapeutic targets for oxygen-ozone treatment // Mech Ageing Dev. 2020. Vol. 186. P. 111210. EDN: BIDSKP doi: 10.1016/j.mad.2020.111210

[31] Scassellati C, Galoforo AC, Esposito C, et al. Promising intervention approaches to potentially resolve neuroinflammation and steroid hormones alterations in Alzheimer’s disease and its neuropsychiatric symptoms. Aging Dis. 2021;12(5):1337–1357. doi: 10.14336/AD.2021.0122

[32] Scassellati C., Galoforo A.C., Esposito C., et al. Promising intervention approaches to potentially resolve neuroinflammation and steroid hormones alterations in Alzheimer’s disease and its neuropsychiatric symptoms // Aging Dis. 2021. Vol. 12, N 5. P. 1337–1357. doi: 10.14336/AD.2021.0122

[33] Shafiee A, Seighali N, Teymouri Athar M, et al. Levels of brain-derived neurotrophic factor (BDNF) among patients with COVID-19: A systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2024;274(5):1137–1152. EDN: CLHGLX doi: 10.1007/s00406-023-01681-z

[34] Shafiee A., Seighali N., Teymouri Athar M., et al. Levels of brain-derived neurotrophic factor (BDNF) among patients with COVID-19: A systematic review and meta-analysis // Eur Arch Psychiatry Clin Neurosci. 2023. Vol. 274, N 5. P. 1137–1152. EDN: CLHGLX doi: 10.1007/s00406-023-01681-z

[35] Keifer J. Regulation of AMPAR trafficking in synaptic plasticity by BDNF and the impact of neurodegenerative disease. J Neurosci Res. 2022;100(4):979–991. EDN: NJVIGA doi: 10.1002/jnr.25022

[36] Keifer J. Regulation of AMPAR trafficking in synaptic plasticity by BDNF and the impact of neurodegenerative disease // J Neurosci Res. 2022. Vol. 100, N 4. P. 979–991. EDN: NJVIGA doi: 10.1002/jnr.25022

[37] Demir B, Beyazyüz E, Beyazyüz M, et al. Long-lasting cognitive effects of COVID-19: Is there a role of BDNF? Eur Arch Psychiatry Clin Neurosci. 2023;273(6):1339–1347. EDN: MDIAYV doi: 10.1007/s00406-022-01514-5

[38] Demir B., Beyazyüz E., Beyazyüz M., et al. Long-lasting cognitive effects of COVID-19: Is there a role of BDNF? // Eur Arch Psychiatry Clin Neurosci. 2023. Vol. 273, N 6. P. 1339–1347. EDN: MDIAYV doi: 10.1007/s00406-022-01514-5

[39] Tanashjan MM, Kuznecova PI, Raskurazhev AA, Zaslavskaja KJ. The structure of post/long covid fatigue syndrome. Prospects for correction. Terapevticheskii arkhiv = Therapeutic archive. 2023;95(5):418–424. EDN: BYFGQA doi: 10.26442/00403660.2023.05.202224

[40] Танашян М.М., Кузнецова П.И., Раскуражев А.А., Заславская К.Я. Структура постковидного астенического синдрома. Перспективы коррекции // Терапевтический архив. 2023. Т. 95, № 5. С. 418–424. EDN: BYFGQA doi: 10.26442/00403660.2023.05.202224

[41] Kopecek M, Stepankova H, Lukavsky J, et al. Montreal Cognitive Assessment (MoCA): Normative data for old and very old czech adults. Applied Neuropsychology: Adult. 2016;24(1):23–29. doi: 10.1080/23279095.2015.1065261

[42] Kopecek M., Stepankova H., Lukavsky J., et al. Montreal Cognitive Assessment (MoCA): Normative data for old and very old czech adults// Applied Neuropsychology: Adult. 2016. Vol. 24, N 1. P. 23–29. doi: 10.1080/23279095.2015.1065261

[43] Coppola L, Luongo C, Pastore A, et al. Ozonized autohaemotransfusion could be a potential rapid-acting antidepressant medication in elderly patients. Int J Geriatr Psychiatry. 2010;25(2):208–213. doi: 10.1002/gps.2322

[44] Coppola L., Luongo C., Pastore A., et al. Ozonized autohaemotransfusion could be a potential rapid-acting antidepressant medication in elderly patients // Int J Geriatr Psychiatry. 2010. Vol. 25, N 2. P. 208–213. doi: 10.1002/gps.2322

[45] Gumenjuk LN, Ternovaja AI, Parshikova VO, et al. Comparative analysis of the effectiveness of balneotherapy and balneotherapy in combination with magnetic laser therapy at the SPA stage of treatment of patients with true eczema. Medicina. Sociologija. Filosofija. Prikladnye issledovanija. 2023;(3):59–65. EDN: XBZTVE

[46] Гуменюк Л.Н., Терновая А.И., Паршикова В.О., и др. Эффективность применения озонотерапии у пациентов с постковидным синдромом на этапе санаторно-курортного лечения // Медицина. Социология. Философия. Прикладные исследования. 2023. N 3. С. 59–65. EDN: XBZTVE

[47] Cvetkova AV, Koneva ES, Kostenko AA, et al. The role of systemic ozone therapy in the rehabilitation of patients after COVID-19. Voprosy kurortologii, fizioterapii i lechebnoi fizicheskoi kultury = Problems of balneology, physiotherapy and exercise therapy. 2022;99(4-2):22–29. EDN: WJOTSV doi: 10.17116/kurort20229904222

[48] Цветкова А.В., Конева Е.С., Костенко А.А., и др. Роль системной озонотерапии в реабилитации пациентов, перенесших COVID-19 // Вопросы курортологии, физиотерапии и лечебной физической культуры. 2022. Т. 99, № 4-2. С. 22–29. EDN: WJOTSV

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