Issue 23-5, 2024

Original article

https://doi.org/10.38025/2078-1962-2024-23-5-41-51

The Role of Toll-Like Receptor 4 Asp299Gly Genetic Polymorphism in Rehabilitation of Patients with Post-COVID Syndrome

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1 ORCIDLeуla Sh. Dudchenko, 2 ORCIDVladimir A. Beloglazov, 2 ORCIDIgor A. Yatskov, 1,* ORCIDGalina N. Andreeva, 1 ORCIDElena A. Solovyova, 1 ORCIDIrina V. Shulyak

1 Academic Research Institute of Physical Methods of Treatment, Medical Climatology and Rehabilitation named by I.M. Sechenov, Yalta, Russia
2 V.I. Vernadsky Crimean Federal University, Simferopol, Russia


ABSTRACT

INTRODUCTION. The multivariability of the clinical course of post-covid syndrome (PCS) is associated with genetic heterogeneity of the population, which leads to a high interest in the study of genotypes.
AIM. To evaluate the role of Toll-like receptor 4 (TLR4 (Asp229Gly) polymorphism in the formation of PCS and rehabilitation potential.
MATERIALS AND METHODS. The study included 92 patients diagnosed with PCS between the ages of 21 and 75. All patients received a comprehensive clinical, laboratory, functional examination and quality of life assessment at admission and discharge. Deoxyribonucleic acid isolation and allele-specific polymerase chain reaction were performed from whole blood using «Lytech» kits (Russia) according to the manufacturer's instructions. Formation of groups for statistical processing was carried out in accordance with the results of genetic analysis. Patients received comprehensive rehabilitation, including: climatotherapy, exercise therapy, massage, aromatherapy, respiratory therapy. Performance was assessed based on the dynamics of the studied indicators. 
RESULTS AND DISCUSSION. Of the 92 patients included in the study, 22 (23.9 %) were AA homozygotes, 33 (35.8 %) were GG, and 37 (40.3 %) were AG heterozygotes. By age, the groups were comparable. The gender ratio was predominantly female in all groups. According to the initial characteristics, the condition of patients with more pronounced clinical symptoms was in the group of patients with the AG genotype. All groups showed varying degrees of positive dynamics. The dependence of the severity of PCS and the effectiveness of rehabilitation on genetic predisposition was established. Different severity of initial clinical symptoms and deviations of functional parameters were revealed. Significant differences were found when assessing the effectiveness of rehabilitation. Positive dynamics was observed in all groups, but most successfully in the AG group. This confirms the role of TLR4 in the immunological response to SARS-CoV-2 and its genetic polymorphism in a wide range of manifestations of both acute COVID-19 and PCS.
CONCLUSIONS. The effectiveness of rehabilitation in patients with PCS is interrelated with the genetic heterogeneity of TLR4. The heterozygous variant of the AG genotype forms more pronounced clinical manifestations of PCS, but also a higher rehabilitation potential, which contributes to the successful completion of rehabilitation. The minor allele TLR4 (Asp299Gly) G is associated with a worsening of the course of PCS. Patients with the homozygous GG genotype need a longer course of rehabilitation.


KEYWORDS: Toll-like receptor 4 (TLR4), genetic polymorphism, post-covid syndrome, rehabilitation

FUNDING: The authors declare no external funding in the conduct of the study.

CONFLICT OF INTEREST: The authors declare no apparent or potential conflicts of interest related to the publication of this article.

FOR CITATION:

Dudchenko L.Sh., Beloglazov V.A., Yatskov I.A., Andreeva G.N., Solovyova E.A., Shulyak I.V. The Role of Toll-Like Receptor 4 Asp299Gly Genetic Polymorphism in Rehabilitation of Patients with Post-COVID Syndrome. Bulletin of Rehabilitation Medicine. 2024; 23(5):41-51. https://doi.org/10.38025/2078-1962-2024-23-5-41-51 (In Russ.).

FOR CORRESPONDENCE:

Galina N. Andreeva, E-mail: galinaandreeva2901@internet.ru, niisechenova@mail.ru


References:

  1. Белоглазов В.А., Яцков И.А., Усеинова Р.Х. Экспрессия и полиморфизм рецепторов TLR4 в патогенезе хронической обструктивной болезни легких: современный взгляд. Медицинская иммунология. 2021; 23(2): 231–236. https://doi.org/10.15789/1563-0625-EAP-2147 [Beloglazov V.A., Yatskov I.A., Useinova R.H. Expression and polymorphism of lTLR4 receptors in pathogenesis of chronic obstructive pulmonary disease: a modern view. Medical Immunology (Russia). 2021; 23(2): 231–236 https://doi.org/10.15789/1563-0625-EAP-2147 (In Russ.).]
  2. Aboudounya M.M., Heads R.J. COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation. Mediators of inflammation. 2021; 2021(1): 8874339. https://doi.org/10.1155/2021/8874339
  3. Евдокимов А.В., Суслова Т.А., Беляева С.В. и др. Полиморфизм генов TLR и течение двусторонней пневмонии при COVID-19. Медицинский академический журнал. 2021; 21(4): 57–66. https://doi.org/10.17816/MAJ90324 [Evdokimov A.V., Suslova T.A., Belyaeva S.V., et al. Polymorphism of TLR genes and the course of COVID-19 bilateral pneumonia. Medical academic journal. 2021; 21(4): 57–66. https://doi.org/10.17816/MAJ90324 (In Russ.).] 
  4. Воропай А.А., Левкович М.А., Галкина Г.А. и др. Роль полиморфизма генов TLR2, TLR4 в формировании микрососудистых осложнений у подростков с сахарным диабетом 1-го типа. Медицинская иммунология. 2021; 23(4): 895–902. https://doi.org/10.15789/1563–0625-ROT-2271 [Voropai A.A., Levkovich M.A., Galkina G.A. Role of TLR2, TLR4 gene polymorphism in developing microvascular complicftions in adolescents with type 1 diabetes mellitus. Medical Immunology (Russia). 2021; 23(4): 895–902. https://doi.org/10.15789/1563-0625-ROT-2271 (In Russ.).] 
  5. Taha S.I., Shata A.K., Baioumy S.A., et al. Toll-Like Receptor 4 Polymorphisms (896A/G and 1196C/T) as an Indicator of COVID-19 Severity in a Convenience Sample of Egyptian Patients. Journal of inflammation research. 2021; 14: 6293–6303. https://doi.org/10.2147/JIR.S343246
  6. Frija-Masson J., Debray M.P., Gilbert M., et al. Functional characteristics of patients with SARS-CoV-2 pneumonia at 30 days post-infection. The European respiratory journal. 2020; 56(2): 2001754. https://doi.org/10.1183/13993003.01754-2020 
  7. Щукина Е.В., Шестерина Ю.Б., Майлян Д.Э. и др. Роль системного воспаления в реализации риска тяжелого течения коронавирусной инфекции и вероятности развития постковидного синдрома. Актуальные проблемы медицины. 2023; 46(2): 113–122. https://doi.org/10.52575/2687-0940-2023-46-2-113-122 [Shchukina E.V., Shesterina Yu.B., Maylyan D.E., et al. The Role of Inflammation in Realizing the Risk of Severe Coronavirus Infection and Probability of Post-COVID-19 Syndrome Initiation. Challenges in Modern Medicine. 2023; 46(2): 113–122. https://doi.org/10.52575/2687-0940-2023-46-2-113-122 (In Russ.).]
  8. Maamar M., Artime A., Pariente E., et al. Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study. Curr Med Res Opin. 2022; 38(6): 901–909. https://doi.org/10.1080/03007995.2022.2042991
  9. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. American Journal of Respiratory and Critical Care Medicine. 2002; 166(1): 111–117. https://doi.org/10.1164/ajrccm.166.1.at1102 
  10. Временные методические рекомендации Минздрава России. Медицинская реабилитация при новой коронавирусной инфекции (COVID-19). Версия 3 (01.11.2022). Доступно на: https://clck.ru/3DFSsS (Дата обращения 01.01.2024). [Vremennye metodicheskie rekomendacii Minzdrava Rossii. Medicinskaya reabilitaciya pri novoj koronavirusnoj infekcii (COVID-19). Versiya 3 (01.11.2022) Available at: https://clck.ru/3DFSsS (Accessed January 12, 2024) (In Russ.).]
  11. Исаева А.В., Ветлужская М.В., Коробейникова А.Н. и др. Клинические фенотипы и особенности течения постковидного синдрома. Профилактическая медицина. 2023;26(9): 66–73. https://doi.org/10.17116/profmed20232609166 [Isaeva A.V., Vetluzhskaya M.V., Korobeynikova A.N., et al. Clinical phenotypes and features of the post-COVID syndrome course. The Russian Journal of Preventive Medicine. 2023; 26(9): 66–73. https://doi.org/10.17116/profmed20232609166 (In Russ.).]
  12. Тюрин И.Е., Струтынская А.Д. Визуализация изменений в легких при коронавирусной инфекции (обзор литературы и собственные данные). Пульмонология. 2020; 30 (5): 658–670. https://doi.org/10.18093/0869-0189-2020-30-5-658-670 [Tyurin I.E., Strutynskaya A.D. Imaging of lung pathology in COVID-19 (literature review and own data). Pulmonologiya. 2020; 30(5): 658–670. 2020; 30 (5): 658–670. https://doi.org/10.18093/0869-0189-2020-30-5-658-670 (In Russ.).]
  13. Rifai N., Ridker P.M. Population distributions of C-reactive protein in apparently healthy men and women in the United States: implication for clinical interpretation. Clinical chemistry. 2003; 49(4): 666–669. https://doi.org/10.1373/49.4.666
  14. Imhof A., Fröhlich M., Loewel H., et al. Distributions of C-reactive protein measured by high-sensitivity assays in apparently healthy men and women from different populations in Europe. Clinical chemistry. 2003; 49(4): 669–672. https://doi.org/10.1373/49.4.669
  15. Кытикова О.Ю., Новгородцева Т.П., Денисенко Ю.К. и др. Толл-подобные рецепторы в патофизиологии ожирения. Ожирение и метаболизм. 2020; 17(1): 56–63. https://doi.org/10.14341/omet10336 [Kytikova O.Yu., Novgorodtseva T.Р., Denisenko Yu.К., et al. Toll-like receptors in the pathophysiology of obesity. Obesity and metabolism. 2020; 17(1): 56–63. https://doi.org/10.14341/omet10336 (In Russ.).]
  16. Кантемирова Б.И., Василькова В.В. Полиморфизм генов у больных новой коронавирусной инфекцией COVID-19. Инфекционные болезни: новости, мнения, обучение. 2022; 11(3): 130–137. https://doi.org/10.33029/2305-3496-2022-11-3-130-137 [Kantemirova B.I., Vasilkova V.V. Polymorphism of genes in patients with new coronavirus infection COVID-19. Infectious Diseases: News, Opinions, Training. 2022; 11(3): 130–137. https://doi.org/10.33029/2305-3496-2022-11-3-130-137 (In Russ.).]
  17. Смирнова С.В., Сальникова Л.Е. Риск развития пневмонии и полиморфизма генов TLR2 и TLR4: мета-анализ. Общая реаниматология. 2015; 11(6): 6–18. https://doi.org/10.15360/1813-9779-2015-6-6-18 [Smirnova S.V., Salnikova L.E. Risk for pneumonia and gene polymorphisms TLR2 and TLR4: meta-analysis. General Reanimatology. 2015; 11(6): 6–18. https://doi.org/10.15360/1813-9779-2015-6-6-18 (In Russ.).]
  18. Torres-Castro R., Vasconcello-Castillo L., Alsina-Restoy X., et al. Respiratory function in patients post-infection by COVID-19: a systematic review and meta-analysis. Pulmonology. 2021; 27 (4): 328–337. https://doi.org/10.1016/j.pulmoe.2020.10.013 
  19. Савушкина О.И., Черняк А.В., Крюков Е.В. и др. Динамика функционального состояния системы дыхания через 4 месяца после перенесенного COVID-19. Пульмонология. 2021; 31 (5): 580–587. https://doi.org/10.18093/0869-0189-2021-31-5-580-587 [Savushkina O.I., Chernjak A.V., Krjukov E.V. et al. Dinamika funkcional'nogo sostojanija sistemy dyhanija cherez 4 mesjaca posle perenesennogo COVID-19. Pulmonologiya. 2021; 31 (5): 580–587. https://doi.org/10.18093/0869-0189-2021-31-5-580-587 (In Russ.).]



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This is an open article under the CC BY 4.0 license. Published by the National Medical Research Center for Rehabilitation and Balneology.