«Long COVID» Molecular Genetic Markers in Patients with Type 2 Diabetes Mellitus

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Aleksandr L. Urakov Yulia A. Sorokina Lubov V. Lovtsova


Coronavirus infection influences on multiple organs and contributes to the progression of concurrent diseases. The most notable and outstanding changes and COVID complications appear in patients with pre – existing cardiovascular and metabolic disturbances especially in elderly. There is evidence that acute viral as well as chronical diseases promote rapid cell senescence and prolong the process of recovery from disease. This review reflects the main common points and axis joining the pre-existing diseases and coronavirus infections complications and resolution. Diabetes mellitus type 2 and cardiovascular diseases (hypertension) predispose to severe outcome of the disease and the COVID-19 mortality risk. The Klotho protein level may be promising predictor of COVID severity and complications in many patients. In order to control properly the rehabilitation process and estimate the level of treatment efficacy we tried to reflect the property of milestone clue biomarker of senescence and cell damage – Klotho protein.

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URAKOV, Aleksandr L.; SOROKINA, Yulia A.; LOVTSOVA, Lubov V.. «Long COVID» Molecular Genetic Markers in Patients with Type 2 Diabetes Mellitus. Medical Research Archives, [S.l.], v. 10, n. 7, july 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2933>. Date accessed: 08 aug. 2022. doi: https://doi.org/10.18103/mra.v10i7.2933.
Research Articles


1. Hugon J, Msika EF, Queneau M, Farid K, Paquet C. Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex. J Neurol. 2022;269(1):44-46. doi:10.1007/s00415-021-10655-x
2. Carod-Artal FJ. Post-COVID-19 syndrome: epidemiology, diagnostic criteria and pathogenic mechanisms involved. Síndrome post-COVID-19: epidemiología, criterios diagnósticos y mecanismos patogénicos implicados. Rev Neurol. 2021;72(11):384-396. doi:10.33588/rn.7211.2021230
3. Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 2021;53(10):737-754. doi:10.1080/23744235.2021.1924397
4. Aiyegbusi OL, Hughes SE, Turner G, et al. Symptoms, complications and management of long COVID: a review. J R Soc Med. 2021;114(9):428-442. doi:10.1177/01410768211032850
5. Raj SR, Arnold AC, Barboi A, et al. Long-COVID postural tachycardia syndrome: an American Autonomic Society statement. Clin Auton Res. 2021;31(3):365-368. doi:10.1007/s10286-021-00798-2
6. Sykes DL, Holdsworth L, Jawad N, Gunasekera P, Morice AH, Crooks MG. Post-COVID-19 Symptom Burden: What is Long-COVID and How Should We Manage It?. Lung. 2021;199(2):113-119. doi:10.1007/s00408-021-00423-z
7. Hussain A, Bhowmik B, do Vale Moreira NC. COVID-19 and diabetes: Knowledge in progress. Diabetes Res Clin Pract. 2020;162:108142. doi:10.1016/j.diabres.2020.108142
8. Chen J, Wu C, Wang X, Yu J, Sun Z. The Impact of COVID-19 on Blood Glucose: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2020;11:574541. Published 2020 Oct 5. doi:10.3389/fendo.2020.574541
9. Lee S, Yu Y, Trimpert J, et al. Virus-induced senescence is a driver and therapeutic target in COVID-19. Nature. 2021;599(7884):283-289. doi:10.1038/s41586-021-03995-1
10. Zheng Y, Liu X, Le W, et al. A human circulating immune cell landscape in aging and COVID-19. Protein Cell. 2020;11(10):740-770. doi:10.1007/s13238-020-00762-2
11. Nehme J, Borghesan M, Mackedenski S, Bird TG, Demaria M. Cellular senescence as a potential mediator of COVID-19 severity in the elderly. Aging Cell. 2020;19(10):e13237. doi:10.1111/acel.13237
12. Midha A, Pan H, Abarca C, et al. Unique Human and Mouse β-Cell Senescence-Associated Secretory Phenotype (SASP) Reveal Conserved Signaling Pathways and Heterogeneous Factors. Diabetes. 2021;70(5):1098-1116. doi:10.2337/db20-0553
13. Lopes-Paciencia S, Saint-Germain E, Rowell MC, Ruiz AF, Kalegari P, Ferbeyre G. The senescence-associated secretory phenotype and its regulation. Cytokine. 2019;117:15-22. doi:10.1016/j.cyto.2019.01.013
14. Schafer MJ, Zhang X, Kumar A, et al. The senescence-associated secretome as an indicator of age and medical risk. JCI Insight. 2020;5(12):e133668. Published 2020 Jun 18. doi:10.1172/jci.insight.133668
15. Lee S, Yu Y, Trimpert J, et al. Virus-induced senescence is a driver and therapeutic target in COVID-19. Nature. 2021;599(7884):283-289. doi:10.1038/s41586-021-03995-1
16. Müller L, Di Benedetto S. How Immunosenescence and Inflammaging May Contribute to Hyperinflammatory Syndrome in COVID-19. Int J Mol Sci. 2021;22(22):12539. Published 2021 Nov 21. doi:10.3390/ijms222212539
17. Sinha S, Castillo V, Espinoza CR, et al. COVID-19 lung disease shares driver AT2 cytopathic features with Idiopathic pulmonary fibrosis. Preprint. bioRxiv. 2022;2021.11.28.470269. Published 2022 Feb 28. doi:10.1101/2021.11.28.470269
18. Klotho therapeutics https://www.klotho.com/ (access 09.06.2022)
19. Gallo Marin B, Aghagoli G, Lavine K, et al. Predictors of COVID-19 severity: A literature review. Rev Med Virol. 2021;31(1):1-10. doi:10.1002/rmv.2146
20. Chen Y, Klein SL, Garibaldi BT, et al. Aging in COVID-19: Vulnerability, immunity and intervention. Ageing Res Rev. 2021;65:101205. doi:10.1016/j.arr.2020.101205
21. Piotrowicz K, Gąsowski J, Michel JP, Veronese N. Post-COVID-19 acute sarcopenia: physiopathology and management. Aging Clin Exp Res. 2021;33(10):2887-2898. doi:10.1007/s40520-021-01942-8
22. Lynch SM, Guo G, Gibson DS, Bjourson AJ, Rai TS. Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease. Cells. 2021;10(12):3367. Published 2021 Nov 30. doi:10.3390/cells10123367
23. Meftahi GH, Jangravi Z, Sahraei H, Bahari Z. The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame-aging". Inflamm Res. 2020;69(9):825-839. doi:10.1007/s00011-020-01372-8
24. Fang X, Li S, Yu H, et al. Epidemiological, comorbidity factors with severity and prognosis of COVID-19: a systematic review and meta-analysis. Aging (Albany NY). 2020;12(13):12493-12503. doi:10.18632/aging.103579
25. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232. doi:10.1016/S0140-6736(20)32656-8
26. Shafie, A., Rahimi, A.M., Ahmadi, I. et al. High-protein and low-calorie diets improved the anti-aging Klotho protein in the rats’ brain: the toxic role of high-fat diet. Nutr Metab (Lond) 17, 86 (2020). https://doi.org/10.1186/s12986-020-00508-1
27. Kuro-O M. The Klotho proteins in health and disease. Nat Rev Nephrol. 2019;15(1):27-44. doi:10.1038/s41581-018-0078-3
28. Navarro-García JA, Fernández-Velasco M, Delgado C, et al. PTH, vitamin D, and the FGF-23-klotho axis and heart: Going beyond the confines of nephrology. Eur J Clin Invest. 2018;48(4):10.1111/eci.12902. doi:10.1111/eci.12902
29. Kuro-o M. Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism. Nat Rev Nephrol. 2013;9(11):650-660. doi:10.1038/nrneph.2013.111
30. Barbu E, Popescu MR, Popescu AC, Balanescu SM. Inflammation as A Precursor of Atherothrombosis, Diabetes and Early Vascular Aging. Int J Mol Sci. 2022;23(2):963. Published 2022 Jan 16. doi:10.3390/ijms23020963
31. Urakov A.L., Sorokina Yu.A., Lovtsova L.V., Makarova E.V., Zanozina O.V. Novel Predictors for Personalized Pharmacotherapy in Type 2 Diabetes and COPD. Advances in Bioresearch. 2021;12(2): 241-245. http://soeagra.com/abr/abrmarch2021/35.pdf.
32. Urakov A, Urakova N. COVID-19: Cause of death and medications. IP Int J Comprehensive Adv Pharmacol 2020;5(2):45-48 https://doi.org/10.18231/j.ijcaap.2020.011