CHANGES IN THE MOLECULAR GENETIC PROFILE OF INNATE IMMUNE MOLECULES IN INDIVIDUALS WHO HAVE HAD COVID-19 DISEASE
https://doi.org/10.15789/1563-0625-CIT-3149
Abstract
Abstract
Introduction. In 2020 COVID-19 was declared to be a pandemic. Since then it was revealed that the severity of the disease pathology may depend not only on the viral strain, but also on the functioning of the immune system. Target. To study characteristics of expression and genetic factors of innate immunity in patients who have had COVID-19. Materials and methods. Material (scrapings from the mucous membranes and venous blood) from 148 patients was studied. Identification of the studied markers was carried out using reverse transcription and RT-PCR methods. Statistical analysis of the results was carried out using the Mann-Whitney test, Fisher's exact test, χ2 test, odds ratio and 95% confidence interval. Results. Our study demonstrated the prognostic role of polymorphic markers and haplotypes in the TLR9 (rs352140 and rs5743836) and TLR4 (rs11536889 and rs4986791) genes in relation to the risk of developing severe SARS-CoV-2 infection. As the result of studying the long-term effects of COVID-19 it was revealed that an imbalance in the expression of receptor and effector molecules at the mucosal level of the immune system remains in patients who have had the disease. There is a decrease in the expression level of both receptor molecules (TLR3, TLR7) and antiviral immune response factors (IL28) in the mucous membranes of the oropharynx with the background of a general increase of these markers in the epithelial cells of the nasopharyngeal mucosa. Conclusion. The expression and genetic factors of innate immunity leading to severe SARS-CoV-2 infection and, consequently, persistent changes in the immune system long after recovery, have been studied, which expands our knowledge of the molecular genetic mechanisms associated with the long-term course of COVID-19. The results obtained during the study can help assess the risks of developing severe infection caused by SARS-CoV-2 and developing complications in hospitalized patients.
About the Authors
N. D. AbramovaRussian Federation
Junior Researcher, Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution I. I. MechnikovResearch Institute ofVaccines and Serums
N. O. Kalyuzhnaya
Russian Federation
Junior Researcher, Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution I. I.Mechnikov Research Institute of Vaccines and Serums
E. A. Meremianina
Russian Federation
Ph.D. (medical science), Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution I. I. Mechnikov Research Institute of Vaccines and Serums, Senior Lecturer, Department of Virology, Russian Medical Academy of Continuing Professional Education
E. A. Bogdanova
Russian Federation
PhD (medical science), Associate Professor of the Department of Microbiology, Immunology and Virology named after A.A. Vorobyov, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenovskiy University)
M. P. Kostinova
Russian Federation
MD, Professor, corresponding member RAS, Head of Laboratory, I. I. Mechnikov Research Institute of Vaccines and Serums; Professor of Department, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
O. A. Sviticha
Russian Federation
MD, professor of RAS, corresponding member. RAS, Director of the Federal State Budgetary Scientific Institution I. I.Mechnikov Research Institute of Vaccines and Serums ,Professor of the Department of Microbiology, Virology and Immunology named after Academician A.A. Vorobyov, First Moscow State Medical University named after I.M. Sechenov of the Ministry of Health of Russia
References
1. Abramova N.D., Soshchenko T.D., Meremyanina E.A., Solntseva V.K., Zheleznyak V.N., Svitich O.A. Expression of innate immunity TLR3 and TLR7 receptors at the level of the upper respiratory airways’ mucosa in patients with severe COVID-19 // Therapy. 2023. Vol. 9. no. 2. pp. 7-13.
2. Abramova N.D., Meremyanina E.A., Kalyuzhnaya N.O., Poddubikov A.V., Kostinov M.P., Grechenko V.V., Svitich O.A. Сytokine expression and production in severe cases of SARS-CoV-2 infection // Russian Journal of Immunology. 2023. Vol. 26. no. 4. pp. 603-610.
3. Akbarialiabad H, Taghrir MH, Abdollahi A, Ghahramani N, Kumar M, Paydar S, Razani B, Mwangi J, Asadi-Pooya AA, Malekmakan L, Bastani B. Long COVID, a comprehensive systematic scoping review// Infection. 2021. Vol. 6 pp.1163-1186.
4. Barison A, Aimo A, Castiglione V, Arzilli C, Lupón J, Codina P, Santiago-Vacas E, Cediel G, Emdin M, Bayes-Genis A. Cardiovascular disease and COVID-19: les liaisons dangereuses.// Eur J Prev Cardiol. 2020 Vol.27 no.10 pp.1017-1025.
5. Botos I, Liu L, Wang Y, Segal DM, Davies DR. The toll-like receptor 3:dsRNA signaling complex.// Biochim Biophys Acta. 2009 no.1789(9-10) pp.667-74.
6. Cañas CA. The triggering of post-COVID-19 autoimmunity phenomena could be associated with both transient immunosuppression and an inappropriate form of immune reconstitution in susceptible individuals.// Med Hypotheses. 2020 Vol.145 pp.110345.
7. Chen Y, Lin J, Zhao Y, Ma X, Yi H. Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses.// J Zhejiang Univ Sci B. 2021 Vol.22 no.8 pp.609-632.
8. Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re'em Y, Redfield S, Austin JP, Akrami A. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact.// EClinicalMedicine. 2021 no.38 pp.101019.
9. Fathi F, Sami R, Mozafarpoor S, Hafezi H, Motedayyen H, Arefnezhad R, Eskandari N. Immune system changes during COVID-19 recovery play key role in determining disease severity. //Int J Immunopathol Pharmacol. 2020 Vol. 34 pp.2058738420966497.
10. Kawai T, Akira S. Signaling to NF-kappaB by Toll-like receptors. //Trends Mol Med. 2007 Vol.13 no.11 pp.460-9.
11. Kawasaki T, Kawai T. Toll-like receptor signaling pathways.// Front Immunol. 2014 Vol.25 no.5 pp.461.
12. Khanmohammadi S, Rezaei N. Role of Toll-like receptors in the pathogenesis of COVID-19.// J Med Virol. 2021 Vol.93 no.5 pp.2735-2739.
13. Lee BL, Barton GM. Trafficking of endosomal Toll-like receptors.//Trends Cell Biol. 2014 Vol. 24 no.6 pp.360-9.
14. Luo XH, Zhu Y, Mao J, Du RC. T cell immunobiology and cytokine storm of COVID-19.// Scand J Immunol. 2021 Vol. 93 no.3 pp.e12989.
15. Mitsi E, Diniz MO, Reiné J, Collins AM, Robinson RE, Hyder-Wright A, Farrar M, Liatsikos K, Hamilton J, Onyema O, Urban BC, Solórzano C, Belij-Rammerstorfer S, Sheehan E, Lambe T, Draper SJ, Weiskopf D, Sette A, Maini MK, Ferreira DM. Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination.// Nat Commun. 2023 Vol. 26 no.14(1) pp. 6815.
16. Mogensen, Trine H. “Pathogen recognition and inflammatory signaling in innate immune defenses.// Clinical microbiology reviews (2009) Vol. 22 no.2 pp.240-73, Table of Contents.
17. Nguyen H, Gazy N, Venketaraman V. A Role of Intracellular Toll-Like Receptors (3, 7, and 9) in Response to Mycobacterium tuberculosis and Co-Infection with HIV ” //International journal of molecular sciences2020, vol. 21 no.17 pp.6148.
18. Pauwels, N. S., Bracke, K. R., Dupont, L. L., Van Pottelberge, G. R., Provoost, S., Vanden Berghe, T., Vandenabeele, P., Lambrecht, B. N., Joos, G. F., & Brusselle, G. G.). Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD// The European respiratory journal, 2011 Vol. 38 no.5 pp.1019–1028.
19. Puchner, B., Sahanic, S., Kirchmair, R., Pizzini, A., Sonnweber, B., Wöll, E., Mühlbacher, A., Garimorth, K., Dareb, B., Ehling, R., Wenter, J., Schneider, S., Brenneis, C., Weiss, G., Tancevski, I., Sonnweber, T., & Löffler-Ragg, J.. Beneficial effects of multi-disciplinary rehabilitation in postacute COVID-19: an observational cohort study.// European journal of physical and rehabilitation medicine, (2021), Vol. 57 no.2, pp.189–198.
20. Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., Xie, C., Ma, K., Shang, K., Wang, W., & Tian, D. S.. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. //Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, (2020) Vol.71 no.15, pp.762–768.
21. Rajagopala, S. V., Strickland, B. A., Pakala, S. B., Kimura, K. S., Shilts, M. H., Rosas-Salazar, C., Brown, H. M., Freeman, M. H., Wessinger, B. C., Gupta, V., Phillips, E., Mallal, S. A., Turner, J. H., & Das, S. R. Mucosal Gene Expression in Response to SARS-CoV-2 Is Associated with Viral Load.// Journal of virology, 2023 Vol.97 no.2, pp.e0147822.
22. Rao, X., Huang, X., Zhou, Z., & Lin, X. An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. //Biostatistics, bioinformatics and biomathematics, 2013 Vol.3 no.3, pp.71–85
23. Reikine, S., Nguyen, J. B., & Modis, Y. (2014). Pattern Recognition and Signaling Mechanisms of RIG-I and MDA5.// Frontiers in immunology, 2014, Vol.5, pp.342.
24. Scharf, R. E., & Anaya, J. M. (2023). Post-COVID Syndrome in Adults-An Overview.// Viruses, Vol.15 no.3, pp.675.
25. Takaoka, A., & Yamada, T.. Regulation of signaling mediated by nucleic acid sensors for innate interferon-mediated responses during viral infection.//International immunology, 2019, Vol.31, no.8, pp.477–488.
26. Tanaka, T., Narazaki, M., & Kishimoto, T. IL-6 in inflammation, immunity, and disease.// Cold Spring Harbor perspectives in biology, 2014, Vol.6, no.10, pp.a016295.
27. Zhang, G., Nie, S., Zhang, Z., & Zhang, Z. Longitudinal Change of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies in Patients with Coronavirus Disease 2019. //The Journal of infectious diseases, 2020, Vol.222 no.2, pp.183–188.
28. Zhao, Z., Xie, J., Yin, M., Yang, Y., Ding, C., Gao, Y., & Ma, X. Interleukin-6 and severity of COVID-19 patients in Hefei, China.// Medecine et maladies infectieuses, 2020, Vol. 50 no.7, pp. 629–631.
Supplementary files
![]() |
1. 3149 | |
Subject | ||
Type | Other | |
Download
(809KB)
|
Indexing metadata ▾ |
Review
For citations:
Abramova N.D., Kalyuzhnaya N.O., Meremianina E.A., Bogdanova E.A., Kostinova M.P., Sviticha O.A. CHANGES IN THE MOLECULAR GENETIC PROFILE OF INNATE IMMUNE MOLECULES IN INDIVIDUALS WHO HAVE HAD COVID-19 DISEASE. Medical Immunology (Russia). (In Russ.) https://doi.org/10.15789/1563-0625-CIT-3149