The role of COVID-19 in modified cognitive functioning
https://doi.org/10.25789/YMJ.2023.81.25
Abstract
SARS-CoV-2 virus impairs cognitive functions during illness and in long-term periods: from 3 months (in 44% of patients) to one year (in 16.2% - 63% of patients) after recovery. Cognitive deficits are more common in patients with severe COVID-19, especially those treated in the intensive care unit, and with infection duration of more than 28 days. Such consequences are associated with direct impact of SARS-CoV-2 on the functioning of brain neurons and changes mediated by endothelial dysfunction due to impaired blood supply to the cerebral cortex. The long-term results of the viral effect on brain neurons are due to immune responses to the virus multiplying in cells and to changes in the epigenetic regulation of gene expression. The immune response leads to inflammation, which is expressed in the form of encephalitis, encephalopathy, anosmia, hypogeusia and is reflected in the development of cognitive deficit. Epigenetic changes are mediated by virus-induced activation of retroelements that have cis- and trans-effects on genes involved in neurogenesis. SARS-CoV-2 promotes the expression of miRNAs that silence the expression of many genes, thus impairing cognitive functioning. The mechanism of these changes is associated with the effect of the virus on retroelements, which are the sources of miRNAs. Reverse transcriptase and endonuclease of retroelements may be involved in the integration of SARS-CoV-2 into the human genome, which may also affect the change in the expression of genes necessary for cognitive development.
Supporting agencies: The study was supported by the State Contract of the Ministry of Science and Education of RF (№АААА-А16-116020350032-1) with partial support of the Ministry of Science and Higher Education of the Republic of Bashkortostan and the Russian Science Foundation (project no. 17-78-30028).
About the Authors
R. N. Mustafin
Bashkir State Medical University
Russian Federation
Russian Federation
Mustafin Rustam Nailevich – PhD, associate professor
A. V. Kazantseva
Institute of Biochemictry and Genetics; Ufa Federal Research Centre of the Russian Academy of Sciences
Russian Federation
Russian Federation
Kazantseva Anastasiya Valerievna – PhD in Biology, senior researcher; Subdivision
E. K. Khusnutdinova
Institute of Biochemistry and Genetics UFRC RAS; UUST
Russian Federation
Russian Federation
Khusnutdinova Elza Kamilevna – Doctor in Biology, Professor, corresponding member, Director; head of the department
References
1. Abenza Abildúa MJ, Atienza S, Carvalho Monteiro G, et al. 2021. Encephalopathy and encephalitis during acute SARS-CoV-2 infection. Spanish Society of Neurology’s COVID-19 Registry. Neurol (English Ed). 2021;36(2):127-34.
2. Amini A, Vaezmousavi M, Shirvani H. The effectiveness of cognitive-motor training on reconstructing cognitive health components in older male adults, recovered from the COVID-19. Neurol. Sci. 2022;43(2):1395-1403. DOI: 10.1007/s10072-021-05502-w.
3. Andriuta D, Roger PA, Thibault W, et al. COVID-19 encephalopathy: detection of antibodies against SARS-CoV-2 in CSF. J. Neurol. 2020;267:2810-1. DOI:10.1007/s00415-020-09975-1.
4. Ashley J, Cordy B, Lucia D, et al. Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons. Cell. 2018;172(1- 2):262-274.e11. DOI: 10.1016/j.cell.2017.12.022.
5. Bachiller S, Martin YDP, Carrion AM. L1 retrotransposition alter the hippocampal genomic landscape enabling memory formation. Brain Behav. Immun. 2017;64:65-70.
6. Balestrieri E, Minutolo A, Petrone V, et al. Evidence of the pathogenic HERV-W envelope expression in T lymphocytes in association with the respiratory outcome of COVID-19 patients. EBioMedicine. 2021;66:103341. DOI: 10.1016/j.ebiom.2021.103341.
7. Banaz-Yasar F., Steffen G., Hauschild J., et al. LINE-1 retrotransposition events affect endothelial proliferation and migration. Histochem. Cell Biol. 2010;134(6):581-9. DOI: 10.1007/s00418-010-0758-y.
8. Barbosa LC, Goncalves TL, de Araujo LP, et al. Endothelial cells and SARSCoV-2: An intimate relationship. Vascul. Pharmacol. 2021;137:106829. DOI: 10.1016/j.vph.2021.106829.
9. Butowt R, von Bartheld CS. Anosmia in COVID-19: underlying mechanisms and assessment of an olfactory route to brain infection. Neuroscientist. 2021;27(6):582-603. DOI: 10.1177/1073858420956905.
10. Campioni MR, Finkbeiner S. Going retro: ancient viral origins of cognition. Neuron. 2015;86(2):346-8. DOI: 10.1016/j.neuron.2015.04.008.
11. 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.
12. El-Shehawi AM, Alotaibi SS, Elseehy MM. Genomic Study of COVID-19 Corona Virus Excludes Its Origin from Recombination or Characterized Biological Sources and Suggests a Role for HERVS in Its Wide Range Symptoms. Cytol. Genet. 2020;54(6):588-604. DOI: 10.3103/S0095452720060031.
13. Fernandes J, Arida RM, Gomez-Pinilla F. Physical exercise as an epigenetic modulator of brain plasticity and cognition. Neurosci. Biobehav. Rev. 2017;80:443-56. DOI: 10.1016/j.neubiorev.2017.06.012.
14. Fernandez-Castaneda A, Lu P, Geraghty AC, et al. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain. bioRxiv. 2022; 2022.01.07.475453. DOI: 10.1101/2022.01.07.475453.
15. Garcia MA, Barreras PV, Lewis A, et al. Cerebrospinal fluid in COVID-19 neurological complications: Neuroazonal damage, antiSARS-CoV2 antibodies but no evidence of cytokine storm. J. Neurol. Sci. 2021;427:117517.
16. Garcia-Grimshaw M, Chirino-Perez A, Flores-Silva FD, et al. Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: a multivariate causality model analysis. Neurol. Sci. 2022;13:1-13. DOI: 10.1007/s10072-021-05798-8.
17. Garcia-Montojo M, Nath A. HERV-W envelope expression in blood leukocytes as a marker of disease severity of COVID-19. EBioMedicine. 2021;67:103363. DOI: 10.1016/j.ebiom.2021.103363.
18. Gullet JM, Chen Z, O’Shea A, et al. MicroRNA predicts cognitive performance in healthy older adults. Neurobiol. Aging. 2020;95:186-194. DOI: 10.1016/j.neurobiolaging.2020.07.023.
19. Hampshire A, Trender W, Chamberlain SR, et al. Cognitive deficits in people who have recovered from COVID-19. EClinicalMedicine. 2021;39:101044. DOI: 10.1016/j.eclinm.2021.101044.
20. Hashizume S, Nakano M, Kubota K, et al. Mindfulness intervention improves cognitive function in older adults by enhancing the level of miRNA-29c in neuron-derived extracellular vesicles. Sci. Rep. 2021;11(1):21848. DOI: 10.1038/s41598-021-01318-y.
21. Heesakkers H, van der Hoeven JG, Corsten S, et al. Clinical Outomes Among Patients With 1-Year Survival Following Intensive Care Unit Treatment for COVID-19. JAMA. 2022;327(6):559-65. DOI:10.1001/jama.2022.0040.
22. Ire M, Yoshikawa M, Ono R, et al. Cognitive Function Related to the Sirh11/Zcchc16 Gene Acquired from an LTR Retrotransposition in Eutherian. PLoS Genet. 2015;11(9):e1005521. DOI: 10.1371/journal.pgen.1005521.
23. Kandemirli SG, Dogan L, Sarikaya ZT, et al. Brain MRI findings in patients in the intensive care unit with COVID-19 infection. Radiology. 2020;297(1):E232-E235. DOI: 10.1148/radiol.2020201697.
24. Kazantseva AV, Enikeeva RF, Romanova AR, et al. Stress-associated cognitive functioning is controlled by variations in synaptic plasticity genes. Russian Journal of Genetics. 2020;56(1):88-95. DOI: 10.31857/S0016675820010063
25. Kazantseva AV, Enikeeva RF, Davydova YuD, et al. The role of the KIBRA and APOE genes in developing spatial abilities in humans. Vavilov Journal of Genetics and Breeding. 2021;25(8):839-46. DOI: 10.18699/VJ21.097.
26. Kitsou K, Kotanidou A, Paraskevis D, et al. Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients. Microbiol. Spectr. 2021;9(2):e0126021. DOI: 10.1128/Spectrum.01260-21.
27. Klein R, Soung A, Sissoko C, et al. COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis. Res Sq. 2021;rs.3.rs-1031824. DOI: 10.21203/rs.3.rs-1031824/v1.
28. Korb E, Finkbeiner S. Arc in synaptic plasticity: from gene to behavior. Trends Neurosci. 2011;34(11):591-8. DOI: 10.1016/j.tins.2011.08.007.
29. Larsen PA, Hunnicutt KE, Larsen RJ, et al. Warning SINEs: Alu elements, evolution of the human brain, and the spectrum of neurological disease. Chromosome Res. 2018;26(1-2):93-111. DOI: 10.1007/s10577-018-9573-4.
30. Leasure AC, Khan YM, Iyer R, et al. Intracerebral hemorrhage in patients with COVID-19: An Analysis From the COVID-19 Cardiovascular Disease Registry. Stroke. 2021.52(7).e321-e323. DOI: 10.1161/STROKEAHA.121.034215.
31. Lee HE, Huh JW, Kim HS. Bioinformatics Analysis of Evolution and Human Disease Related Transposable Element-Derived microRNAs. Life (Basel). 2020;10:95.
32. Linker SB, Marchetto MC, Narvaiza I, et al. Examining non-LTR retrotransposons in the context of the evolving primate brain. BMC Biol. 2017;15(1):68.
33. Lu SY, Fu CL, Liang L, et al. MiR-218-2 regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release. Proc. Natl. Acad. Sci. USA. 2021;118(14):e2021770118. DOI: 10.1073/pnas.2021770118.
34. Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitaltized Patients With Coronavirus Disease 2019 in Muhan, China. JAMA Neurol. 2020;77(6):683-90. DOI: 10.1001/jamaneurol.2020.1127.
35. Marston JL, Greenig M, Singh M, et al. SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements. JCI Insight. 2021;6(24):e147170. DOI: 10.1172/jci.insight.147170.
36. Mattioli F, Piva S, Stampatori C, et al. Neurologic and cognitive sequelae after SARS-CoV2 infection: Different impairment for ICU patients. J. Neurol. Sci. 2022;432:120061. DOI: 10.1016/j.jns.2021.120061.
37. Meinhardt J, Radke J, Dittmayer C, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat. Neurosci. 2021;24(2):168-75. DOI: 10.1038/s41593-020-00758-5.
38. Mendez R, Balanza-Martinez V, Luperdi SC, et al. Long-term neuropsychiatric outcomes in COVID-19 survivors: A 1-year longitudinal study. J. Intern. Med. 2022;291(2):247-51. DOI: 10.1111/joim.13389.
39. Moretta P, Maniscalco M, Papa A. et al. Cognitive impairment and endothelial dysfunction in convalescent COVID-19 patients undergoing rehabilitation. Eur J Clin Invest. 2022;52(2):e13726. DOI: 10.1111/eci.13726.
40. Muotri AR. L1 Retrotransposition in Neural Progenitor Cells. Methods Mol Biol. 2016;1400:157-63. DOI: 10.1007/978-1-4939-3372-3_11.
41. Mustafin RN, Kazantseva AV, Malykh SB, Khusnutdinova EK Genetic mechanisms of cognitive development. Russian Journal of Genetics. 2020;56(8):891-902. DOI: 10.1134/S102279542007011X.
42. Naville M, Warren IA, Haftek-Terreau Z, et al. Not so bad after all: retroviruses and long terminal repeat retrotransposons as a source of new genes in vertebrates. Clin Microbiol Infect. 2016;22(4):312-23. DOI: 10.1016/j.cmi.2016.02.001.
43. Peebles CL, Yoo J, Thwin MT, et al. Arc regulates spine morphology and maintains network stability in vivo. Proc Natl Acad Sci USA. 2010;107(42):18173-8. DOI: 10.1073/pnas.1006546107.
44. Penner MR, Roth TL, Chawla MK, et al. Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging. 2011;32(12):2198-210. DOI: 10.1016/j.neurobiolaging.2010.01.009.
45. Pranata R, Huang I, Lim MA, et al. Delirium and mortality in coronavirus disease 2019 (COVID-19) A Systematic Review and Meta-analysis. Arch Gerontol Geriatr. 2021;95:104388. DOI: 10.1016/j.archger.2021.104388.
46. Qureshi AI, Baskett WI, Huang W, et al. Acute ischemic stroke and COVID-19: an analysis of 27676 patients. Stroke. 2021;52(3):905- 912. DOI: 10.1161/STROKEAHA.120.031786.
47. Rousseau A, Minguet P., Colson C, et al. Post-intensive care syndrome after a critical COVID-19: cohort study from a Belgian follow-up clinic. Ann. Intensive Care. 2021;11(1):118. DOI: 10.1186/s13613-021-00910-9.
48. Sankowski R, Strohl JJ, Huerta TS, et al. Endogenous retroviruses are associated with hippocampus-based memory impairment. Proc. Natl. Acad. Sci. USA. 2019;116(51):25982-90. DOI: 10.1073/pnas.1822164116.
49. Segel M, Lash B, Song J, et al. Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery. Science. 2021;373(6557):882-9. DOI: 10.1126/science.abg6155.
50. Sing J, Raina A, Sangwan N, et al. Identification of homologous human miRNAs as antivirals towards COVID-19 genome. Adv Cell Gene Ther. 2021;4(4):e114. DOI: 10.1002/acg2.114.
51. Sudre C, Keshet A, Graham MS, et al. Anosmia, ageusia, and other COVID-19-like symptoms in association with a positive SARSCoV-2 test, across six national digital surveillance platforms: an observational study. Lancet Digit. Heal. 2021;3(9):e577-86. DOI: 10.1016/S2589-7500(21)00115-1.
52. Tabacof L, Tosto-Mancuso J, Wood J, et al. Post-acute COVID-19 Syndrome Negatively Impacts Physical Function, Cognitive Function, Health-Related Quality of Life, and Participation. Am. J. Phys. Med. Rehabil. 2022;101(1):48-52. DOI: 10.1097/PHM.0000000000001910.
53. Tovo PA, Garazzino S, Dapra V, et al. COVID-19 in children: expression of type I/II/ III interferons, TRIM28, SETDB1, and endogenous retroviruses in mild and severe cases. Int. J. Mol. Sci. 2021;22(14):7481. DOI: 10.3390/ijms22147481.
54. Wei G, Qin S, Li W, et al. MDTE DB: a database for microRNAs derived from Transposable element. IEEE/ACM Trans. Comput. Biol. Bioinform. 2016;13:1155–60.
55. Woldemichael BT, Mansuy IM. Micro-RNAs in cognition and cognitive disorders: Potential for novel biomarkers and therapeutics. Biochem. Pharmacol. 2016;104:1-7. DOI: 10.1016/j.bcp.2015.11.02.
56. Zhang BZ, Chu H, Han S, et al. SARSCoV-2 infects human neural progenitor cells and brain organoids. Cell Res. 2020;30(10):928-31. DOI: 10.1038/s41422-020-039-x.
57. Zhang J, Sun P, Zhou C, et al. Regulatory microRNAs and vascular cognitive impairment and dementia. CNS Neurosci. Ther. 2020;26(12):1207-18. DOI: 10.1111/cns.13472.
58. Zhang L, Richards A, Barrasa MI, et al. Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues. Proc. Natl. Acad. Sci. 2021;118:e2105968118. DOI: 10.1073/pnas.2105968118.
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Mustafin R.N., Kazantseva A.V., Khusnutdinova E.K. The role of COVID-19 in modified cognitive functioning. Yakut Medical Journal. 2023;(1):100-105. https://doi.org/10.25789/YMJ.2023.81.25
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