Prospects and possibilities for the treatment of patients with long COVID-19 syndrome
- Authors: Tanashyan M.M.1, Raskurazhev A.A.1, Kuznetsova P.I.1, Bely P.A.2, Zaslavskaya K.I.3
-
Affiliations:
- Scientific Center of Neurology
- Yevdokimov Moscow State University of Medicine and Dentistry
- Ogarev National Research Mordovia State University
- Issue: Vol 94, No 11 (2022)
- Pages: 1285-1293
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/232341
- DOI: https://doi.org/10.26442/00403660.2022.11.201981
- ID: 232341
Cite item
Full Text
Abstract
Aim. To study the efficacy and safety of a drug product based on the succinic acid complex with trimethylhydrazine used to treat patients with asthenic syndrome after a new coronavirus infection (COVID-19).
Materials and methods. A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the safety and efficacy of sequential therapy with Brainmax® enrolled 160 patients 12–16 weeks after coronavirus infection (no more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. At the enrollment, clinical and neurological examination and the following tests were performed: complete blood count, urinalysis, blood chemistry, coagulation test, pulse oximetry, electrocardiography, glomerular filtration rate calculation (according to Cockcroft–Gault formula) were performed. Also, the patients were assessed using the following tools: VAS headache rating scale, MFI-20 asthenia scale, PSQI index, FAS-10 fatigue assessment scale, Dizziness Handicap Inventory (DHI), MoCA-test for cognitive impairment assessment, Beck Anxiety Inventory, Kérdö Autonomic Index.
Results. The primary endpoint was the mean reduction in the MFI-20 asthenia scale score after the therapy (Visit 5, 41st day of therapy) compared to data from Visit 0 (beginning of therapy). A clinically significant advantage of the study drug versus the placebo was demonstrated, with a median absolute change in the MFI-20 score of -19.5 [-27; -11] points in the Brainmax® drug group and -3 [-7; 1] score in the placebo group (p<0.001). A significant sleep quality improvement according to the PSQI index was shown in the study group: by -2.5 [-4; -1] points versus no improvement in the placebo group (0 [-3; 0], p<0,001). Significant differences were also noted for the following secondary endpoints: PSQI sleep quality scale, FAS-10 fatigue assessment scale, DHI, and Beck Anxiety and Depression Inventory. There was also a decrease in patients' complaints of cognitive deterioration according to the CGI scale.
Conclusion. Our study clearly demonstrated the efficacy and high safety profile of Brainmax® in a representative sample of patients with the post-COVID syndrome.
Full Text
##article.viewOnOriginalSite##About the authors
Marine M. Tanashyan
Scientific Center of Neurology
Email: angioneurology0@gmail.com
ORCID iD: 0000-0002-5883-8119
чл.-кор. РАН, д-р мед. наук, проф., зам. дир. по научной работе, рук. 1-го неврологического отд-ния
Russian Federation, MoscowAnton A. Raskurazhev
Scientific Center of Neurology
Email: angioneurology0@gmail.com
ORCID iD: 0000-0003-0522-767X
канд. мед. наук, ст. науч. сотр., врач-невролог 1-го неврологического отд-ния
Russian Federation, MoscowPolina I. Kuznetsova
Scientific Center of Neurology
Author for correspondence.
Email: angioneurology0@gmail.com
ORCID iD: 0000-0002-4626-6520
канд. мед. наук, науч. сотр., врач-невролог 1-го неврологического отд-ния
Russian Federation, MoscowPetr A. Bely
Yevdokimov Moscow State University of Medicine and Dentistry
Email: angioneurology0@gmail.com
ORCID iD: 0000-0001-5998-4874
канд. мед. наук, ст. лаборант каф. пропедевтики внутренних болезней и гастроэнтерологии
Russian Federation, MoscowKira Ia. Zaslavskaya
Ogarev National Research Mordovia State University
Email: angioneurology0@gmail.com
ORCID iD: 0000-0002-7348-9412
ассистент каф. биологической и фармацевтической химии с курсом организации и управления фармацией Медицинского института
Russian Federation, SaranskReferences
- Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-33. doi: 10.1056/NEJMoa200101
- Carod-Artal FJ. Post-COVID-19 syndrome: epidemiology, diagnostic criteria and pathogenic mechanisms involved. Rev Neurol. 2021;72(11):384-96. doi: 10.33588/rn.7211.2021230
- WHO Coronavirus (COVID-19) Dashboard. Available at: https://covid19.who.int/ Accessed: 14.11.2022.
- Carod-Artal FJ. Complicaciones neurológicas por coronavirus y COVID-19. Rev Neurol. 2020;70:311-22. doi: 10.33588/rn.7009.2020179
- Танашян М.М., Кузнецова П.И., Раскуражев А.А. Неврологические аспекты COVID19. Анналы клинической и экспериментальной неврологии. 2020;14(2):62-9 [Tanashyan MM, Kuznetsova PI, Raskurazhev AA. Neurological aspects of COVID-19. Annals of Clinical and Experimental Neurology. 2020;14(2):62-9 (in Russian)]. doi: 10.25692/ACEN.2020.2.8
- A clinical case definition of post COVID-19 condition by a Delphi consensus. WHO. 2021;1-27. Available at: https://apps.who.int/iris/bitstream/handle/10665/345824/WHO-2019-nCoV-Post-COVID-19-condition-Clinical-case-definition-2021.1-eng.pdf. Accessed: 14.11.2022.
- Рекомендации по ведению больных с коронавирусной инфекцией COVID-19 в острой фазе и при постковидном синдроме в амбулаторных условиях. Под ред. проф. П.А. Воробьева. Проблемы стандартизации в здравоохранении. 2021;7-8:3-96 [Recommendations for the management of patients with coronavirus infection COVID-19 in the acute phase and in the case of post -acute syndrome in outpatient conditions. Ed. prof. P.A. Vorobyev. Problems of Standardization in Health Care. 2021;7-8:3-96 (in Russian)]. doi: 10.26347/1607-2502202107-08003-096
- Aiyegbusi OL, Hughes SE, Turner G, et al. Symptoms, complications and management of long COVID: a review. J R Soc Med. 2021;114(9):428-42. doi: 10.1177/01410768211032850
- Lopez-Leon S, Wegman-Ostrosky T, Perelman C, et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep. 2021;11(1):16144. doi: 10.1038/s41598-021-95565-8
- Joli J, Buck P, Zipfel S, Stengel A. Post-COVID-19 fatigue: A systematic review. Front Psychiatry. 2022;13:947973. doi: 10.3389/fpsyt.2022.947973
- Crook H, Raza S, Nowell J, et al. Long covid-mechanisms, risk factors, and management. BMJ. 2021;374:n1648. doi: 10.1136/bmj.n1648
- Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995;39(3):315-25. doi: 10.1016/0022-3999(94)00125-o
- Bakalidou D, Krommydas G, Abdimioti T, et al. The Dimensionality of the Multidimensional Fatigue Inventory (MFI-20) Derived From Healthy Adults and Patient Subpopulations: A Challenge for Clinicians. Cureus. 2022;14(6):e26344. doi: 10.7759/cureus.26344
- Ceban F, Ling S, Lui LMW, et al. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022;101:93-135. doi: 10.1016/j.bbi.2021.12.020
- Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-15. doi: 10.1038/s41591-021-01283-z
- Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med. 2021;27(9):895-906. doi: 10.1016/j.molmed.2021.06.002
- Douaud G, Lee S, Alfaro-Almagro F, et al. Brain imaging before and after COVID-19 in UK Biobank. bioRxiv. 2022:2021.06.11.21258690. doi: 10.1101/2021.06.11.21258690
- Lee MH, Perl DP, Nair G, et al. Microvascular injury in the brains of patients with COVID-19. N Engl J Med. 2021;384(5):481-3. doi: 10.1056/NEJMc2033369
- Guedj E, Campion JY, Dudouet P, et al. 18F-FDG brain PET hypometabolism in patients with long COVID. Eur J Nucl Med Mol Imaging. 2021;48(9):2823-33. doi: 10.1007/s00259-021-05215-4
- Безопасность лекарственных препаратов. Режим доступа: grls.rosminzdrav.ru. Ссылка активна на 14.11.2022 [Drug Safety. Available at: grls.rosminzdrav.ru. Accessed: 14.11.2022 (in Russian)].
- Журавлева М.В., Грановская М.В., Заславская К.Я., и др. Синергическое действие препарата с координационным комплексом триметилгидразиния пропионата и этилметилгидроксипиридина сукцината на энергетический обмен и дыхание клетки. Фармация и фармакология. 2022;10(4):387-99 [Zhuravleva MV, Granovskaya MV, Zaslavskaya KY, et al. Synergic effect of preparation with coordination complex “trimethydrazinium propionate+ethymth methylhydroxypiridine succinate” on energy metabolism and cell respiration. Pharmacy & Pharmacology. 2022;10(4):387-99 (in Russian)]. doi: 10.19163/2307-9266-2022-10-4-387-399
- Танашян М.М., Раскуражев А.А., Заславская К.Я., и др. Новые возможности нейропротективной терапии пациентов в остром и раннем восстановительном периоде ишемического инсульта. Терапевтический архив. 2022;94(6):748-55 [Tanashyan MM, Raskurazhev AA, Zaslavskaya KI, et al. New opportunities for neuroprotective therapy of patients in the acute and early recovery period of ischemic stroke. Terapevticheskii Arkhiv (Ter. Arkh.). 2022;94(6):748-55 (in Russian)]. doi: 10.26442/00403660.2022.06.201743
- Статистический отчет, версия 1.0 от 21.09.2022 по результатам «Проспективного многоцентрового сравнительного рандомизированного двойного слепого плацебо-контролируемого исследования безопасности и эффективности последовательной терапии препаратами БРЕЙНМАКС®, раствор для внутривенного и внутримышечного введения и БРЕЙНМАКС® капсулы для лечения пациентов с астенией после перенесенной новой коронавирусной инфекции (COVID-19)» по протоколу № BREINMAX_ 2021, версия 1.0 от 06.12.2021. Режим доступа: https://grlsbase.ru/clinicaltrails/clintrail/12286. Ссылка активна на 14.11.2022 [Statistical report, version 1.0 from 21.09.2022 on the results of the "Prospective Multi-Centre Comparative Double Blind Placebo-Controlled Safety and Efficacy Study of Sequential Therapy by BRAINMAX®, intravenous and intramuscular administration solution and BRAINMAX® capsules for treating patients with asthenia following a new coronavirus infection (COVID-19)» according to protocol BREINMAX_ 2021, version 1.0 of 06.12.2021. Available at: https://grlsbase.ru/clinicaltrails/clintrail/12286 Accessed: 14.11.2022 (in Russian)].
- Акарачкова Е.С. К вопросу диагностики и лечения психовегетативных расстройств в общесоматической практике. Лечащий врач. 2010;10:60-4 [Akarachkova ES. To the question of diagnosis and treatment of psychovegetative disorders in general omatic practice. The Practitioner. 2010;10:60-4 (in Russian)].
- Котова О.В., Акарачкова Е.С. Астенический синдром в практике невролога и семейного врача. РМЖ. 2016;13:824-9 [Kotova OV, Akarachkova ES. Asthenic syndrome in neurological and family doctor practice. RMJ. 2016;13:824-9 (in Russian)].
- Lier J, Stoll K, Obrig H, et al. Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients. Front Neurol. 2022;13:988359. doi: 10.3389/fneur.2022.988359
- Stefano GB, Büttiker P, Weissenberger S, et al. Editorial: The Pathogenesis of Long-Term Neuropsychiatric COVID-19 and the Role of Microglia, Mitochondria, and Persistent Neuroinflammation: A Hypothesis. Med Sci Monit. 2021;27:e933015. doi: 10.12659/MSM.933015
- Bhat S, Chokroverty S. Sleep disorders and COVID-19. Sleep Med. 2022;91:253-61. doi: 10.1016/j.sleep.2021.07.021
- Chouchani ET, Pell VR, Gaude E, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515(7527):431-5. doi: 10.1038/nature13909
Supplementary files
![](/img/style/loading.gif)