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Asymptomatic COVID-19 and structural changes in the brain

Year 2024, Volume: 6 Issue: 1, 59 - 64, 15.01.2024
https://doi.org/10.38053/acmj.1386041

Abstract

Aims: Neurological symptoms are the most prevalent extrapulmonary complications of coronavirus disease 2019 (COVID-19). In this context, the objective of this study is to assess the brain magnetic resonance imaging (MRI) parameters of asymptomatic COVID-19 individuals one year after diagnosed with COVID-19 in comparison with healthy control subjects.
Methods: The population of this prospective study consisted of individuals who have not developed olfactory impairment or other complications within one year after diagnosed with COVID-19. For the study, 8 male, 25 female, 4 male and 23 female individuals were accepted for PCG and CG, respectively, according to the inclusion and exclusion criteria. The mean age was found to be 37.75±11.56 and 37.11±10.67, respectively. All participants included in the study underwent olfactory sulcus (OS) depth, olfactory bulb (OB) volume, hippocampal sclerosis (HS), insular gyrus area, and corpus amygdala area measurements.
Results: The bilateral OB volume, insular gyrus area and corpus amygdala area were significantly lower in the post-COVID-19 group (PCG) than in the control group (CG) (p<0.05). On the other hand, the bilateral OS depth was significantly higher in PCG than in CG (p<0.05). In the PCG, the insular gyrus area and corpus amygdala area values of the right side were significantly higher than those of the left side (p<0.05). In addition, bilateral HS was detected in five patients in the PCG, right-sided HS in two patients, and left-sided HS in one patient.
Conclusion: The findings of this study have shown that COVID-19 infection, albeit asymptomatic, can trigger neurodegeneration. We believe that in the future COVID-19 infection will play a role in the etiopathogenesis of many neurodegenerative diseases.

Ethical Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Ethics Committee) of Hitit University School of Medicine Ethics Committee (2022-17-31/03/2022)

References

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  • Sudre CH, Murray B, Varsavsky T, et al. Attributes and predictors of long COVID. Nat Med. 2021;27(4):626-631. doi:10.1038/s41591-021-01292-y
  • Seyed Alinaghi S, Afsahi AM, MohsseniPour M, et al. Late complications of COVID-19; a systematic review of current evidence. Arch Acad Emerg Med. 2021;9(1):e14. doi:10.22037/aaem.v9i1.1058
  • ACTT-1 Study Group., Remdesivir for the treatment of Covid-19: final report. N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa2007764
  • Ogut E, Armagan K. evaluation of the potential impact of medical ozone therapy on COVID-19: a review study. Ozone: Science & Engineering. 2022;45(3):213-231. doi:10.1080/01919512.2022.2065242
  • Zawilska JB, Kuczyńska K. Psychiatric and neurological complications of long COVID. J Psychiatr Res. 2022;156:349-360. doi: 10.1016/j.jpsychires.2022.10.045
  • Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-1032. doi:10.1038/s41591-020-0968-3
  • Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280. doi: 10.1016/j.cell.2020.02.052
  • Qi F, Qian S, Zhang S, et al. Single-cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020;526(1):135-140. doi:10. 1016/j.bbrc.2020.03.044
  • Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell. 2020;181(5):1016-1035. doi:10.1016/j. cell.2020.04.035
  • Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615. doi:10.1038/s41591-021-01283-z
  • Ehrenfeld M, Tincani A, Andreoli L, et al. COVID-19 and autoimmunity. Autoimmun Rev. 2020;19(8):102597. doi:10.1016/j.autrev.2020.102597
  • Carfì A, Bernabei R, Landi F, et al. Persistent symptoms in patients after acute COVID-19. JAMA 2020;324(6):603-605. doi:10.1001/jama. 2020.12603
  • 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
  • Generoso JS, Barichello de Quevedo JL, Cattani M, et al. Neurobiology of COVID-19: how can the virus affect the brain? Braz J Psychiatry. 2021;43(6):650-664. doi: 10.1590/1516-4446-2020-1488
  • Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol. 2020;19(9):767-783.
  • Winkler AS, Knauss S, Schmutzhard E, et al. A call for a global COVID-19 Neuro Research Coalition. Lancet Neurol. 2020;19(6):482-484.
  • Romero-Sánchez CM, Díaz-Maroto I, Fernández-Díaz E, et al. Neurologic manifestations in hospitalized patients with COVID-19. Neurol. 2020;95(8):e1060-e1070.
  • Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-1418.
  • Douaud G, Lee S, Alfaro-Almagro F, et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022;604(7907):697-707.
  • Crunfli F, Carregari VC, Veras FP, et al. Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. Proc Natl Acad Sci. 2022;119(35):e2200960119. doi: 10.1073/ pnas.2200960119
  • Hugon J, Msika EF, Queneau M, et al. Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex. J Neurol. 2022;269(1):44-46.
  • Doğan A, Burulday V, Alpua M. İdiyopatik Parkinson hastalarında olfaktör bulbus volüm ve olfaktör sulkus derinliğinin manyetik rezonans görüntüleme ile değerlendirilmesi. Kırıkkale Üni Tıp Fak Derg. 2019;21(1):22-27. doi:10.24938/kutfd.429018
  • Altmann J. Autoradiographic and histological studies of postnatal neurogenesis. IV. cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol. 1969;137(4):433-457.
  • Graziadei PPC, Graziadei GM. Neurogenesis and neuronregeneration in the olfactory system of mammals. III. deafferentation and reinnervation of the olfactory bulb following section of the fila olfactoria in rat. J Neurocytol. 1980;9(2):145-162.
  • Takahashi T, Ota M, Numata Y, et al. Relationships between the Fear of COVID-19 Scale and regional brain atrophy in mild cognitive impairment. Acta Neuropsychiatrica. 2022;34(3):153-162.
  • Rebsamen M, Friedli C, Radojewski P, et al. Multiple sclerosis as a model to investigate SARS-CoV-2 effect on brain atrophy. CNS Neurosci Ther. 2023;29(2):538-543. doi: 10.1111/cns.14050
  • Jobin B, Boller B, Frasnelli J. Volumetry of olfactory structures in mild cognitive impairment and Alzheimer’s disease: a systematic review and a meta‐analysis. Brain Sci. 2021;11(8):6-13. doi: 10.3390/brainsci11081010
  • Al-Otaibi M, Lessard-Beaudoin M, Castellano CA, et al. Volumetric MRI demonstrates atrophy of the olfactory cortex in AD. Curr Alzheimer Res. 2021;17(10):904-915.
  • Najt P, Richards HL, Fortune DG. Brain imaging in patients with COVID-19: a systematic review. Brain Behav Immun Health. 2021;16:100290. doi: 10.1016/j.bbih.2021.100290
  • Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18-22. doi: 10.1016/j.bbi.2020. 03.031
  • Lu Y, Li X, Geng D, et al. Cerebral micro-structural changes in COVID-19 patients–an MRI-based 3-month follow-up study. EClinicalMedicine. 2020;25:100484. doi: 10.1016/j.eclinm.2020.100484
  • Rahman A, Tabassum T, Araf Y, et al. Silent hypoxia in COVID-19: pathomechanism and possible management strategy. Mol Biol Rep. 2021;48(4):3863-3869. doi: 10.1007/s11033-021-06358-1
  • Ahmed M, Roy S, Iktidar MA, et al. Post-COVID-19 memory complaints: prevalence and associated factors. Neurología. 2022. doi: 10.1016/j.nrl.2022.03.007
  • Mahajan A, Mason GF. A sobering addition to the literature on COVID-19 and the brain. J Clin Invest. 2021;131(8):e148376. doi: 10.1172/JCI148376
  • Liu X, Yan W, Lu T, Han Y, Lu L. Longitudinal abnormalities in brain structure in COVID-19 patients. Neurosci Bull. 2022;38(12):1608-1612. doi: 10.1007/s12264-022-00913-x
  • Shan D, Li S, Xu R, et al. Post-COVID-19 human memory impairment: a PRISMA-based systematic review of evidence from brain imaging studies. Front Aging Neurosci. 2022;14:1077384. doi: 10.3389/fnagi.2022.1077384.
  • Cecchetti G, Agosta F, Canu E, et al. Cognitive, EEG, and MRI features of COVID-19 survivors: a 10-month study. J Neurol. 2022;269(7):3400-3412. doi: 10.1007/s00415-022-11047-5
  • Ermis U, Rust MI, Bungenberg J, et al. Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients. Neurol Res Pract. 2021;3(1):1-12. doi: 10.1186/s42466-021-00116-1
  • Hadad R, Khoury J, Stanger C, et al. Cognitive dysfunction following COVID-19 infection. J Neurovirol. 2022;28(3):430-437. doi: 10.1007/s13365-022-01079-y
  • Meyer PT, Hellwig S, Blazhenets G, et al. Molecular imaging findings on acute and long-term effects of COVID-19 on the brain: a systematic review. J Nucl Med. 2022;63(7):971-980. doi: 10.2967/jnumed.121.263085
  • Bungenberg J, Humkamp K, Hohenfeld C, et al. Long COVID-19: objectifying most self-reported neurological symptoms. Annal Clin Transl Neurol. 2022;9(2):141-154. doi: 10.1002/acn3.51496
  • Newhouse A, Kritzer MD, Eryilmaz H, et al. Neurocircuitry hypothesis and clinical experience treating neuropsychiatric symptoms of post acute sequelae of SARS-CoV-2 (PASC). J Acad Consult Liaison Psychiatry. 2022;63(6):619-627. doi: 10.1016/j.jaclp.2022. 08.007
  • Tian T, Wu J, Chen T, et al. Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations. JCI Insight. 2022;7(4):e155827. doi: 10.1172/jci.insight.155827
  • Fernández-Castañeda 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
  • Li C, Liu J, Lin J. et al. COVID-19 and risk of neurodegenerative disorders: a Mendelian randomization study. Transl Psychiatry. 2022;12(1):283. doi.org/10.1038/s41398-022-02052-3
  • Rahmati M, Yon DK, Lee SW, et al. New-onset neurodegenerative diseases as long-term sequelae of SARS-CoV-2 infection: a systematic review and meta-analysis. J Med Virol. 2023;95(7):e28909. doi: 10.1002/jmv.28909.
  • Leng A, Shah M, Ahmad SA, et al. Pathogenesis underlying neurological manifestations of long COVID syndrome and potential therapeutics. Cells. 2023;12(5):816. doi.org/10.3390/cells 12050816
Year 2024, Volume: 6 Issue: 1, 59 - 64, 15.01.2024
https://doi.org/10.38053/acmj.1386041

Abstract

References

  • Desai AD, Lavelle M, Boursiquot BC. et al. Long-term complications of COVID-19. Am J Physiol Cell Physiol. 2022; 322(1):C1–C11. doi.org/10.1152/ajpcell.00375.2021
  • Sudre CH, Murray B, Varsavsky T, et al. Attributes and predictors of long COVID. Nat Med. 2021;27(4):626-631. doi:10.1038/s41591-021-01292-y
  • Seyed Alinaghi S, Afsahi AM, MohsseniPour M, et al. Late complications of COVID-19; a systematic review of current evidence. Arch Acad Emerg Med. 2021;9(1):e14. doi:10.22037/aaem.v9i1.1058
  • ACTT-1 Study Group., Remdesivir for the treatment of Covid-19: final report. N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa2007764
  • Ogut E, Armagan K. evaluation of the potential impact of medical ozone therapy on COVID-19: a review study. Ozone: Science & Engineering. 2022;45(3):213-231. doi:10.1080/01919512.2022.2065242
  • Zawilska JB, Kuczyńska K. Psychiatric and neurological complications of long COVID. J Psychiatr Res. 2022;156:349-360. doi: 10.1016/j.jpsychires.2022.10.045
  • Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-1032. doi:10.1038/s41591-020-0968-3
  • Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280. doi: 10.1016/j.cell.2020.02.052
  • Qi F, Qian S, Zhang S, et al. Single-cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020;526(1):135-140. doi:10. 1016/j.bbrc.2020.03.044
  • Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell. 2020;181(5):1016-1035. doi:10.1016/j. cell.2020.04.035
  • Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615. doi:10.1038/s41591-021-01283-z
  • Ehrenfeld M, Tincani A, Andreoli L, et al. COVID-19 and autoimmunity. Autoimmun Rev. 2020;19(8):102597. doi:10.1016/j.autrev.2020.102597
  • Carfì A, Bernabei R, Landi F, et al. Persistent symptoms in patients after acute COVID-19. JAMA 2020;324(6):603-605. doi:10.1001/jama. 2020.12603
  • 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
  • Generoso JS, Barichello de Quevedo JL, Cattani M, et al. Neurobiology of COVID-19: how can the virus affect the brain? Braz J Psychiatry. 2021;43(6):650-664. doi: 10.1590/1516-4446-2020-1488
  • Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol. 2020;19(9):767-783.
  • Winkler AS, Knauss S, Schmutzhard E, et al. A call for a global COVID-19 Neuro Research Coalition. Lancet Neurol. 2020;19(6):482-484.
  • Romero-Sánchez CM, Díaz-Maroto I, Fernández-Díaz E, et al. Neurologic manifestations in hospitalized patients with COVID-19. Neurol. 2020;95(8):e1060-e1070.
  • Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-1418.
  • Douaud G, Lee S, Alfaro-Almagro F, et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022;604(7907):697-707.
  • Crunfli F, Carregari VC, Veras FP, et al. Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. Proc Natl Acad Sci. 2022;119(35):e2200960119. doi: 10.1073/ pnas.2200960119
  • Hugon J, Msika EF, Queneau M, et al. Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex. J Neurol. 2022;269(1):44-46.
  • Doğan A, Burulday V, Alpua M. İdiyopatik Parkinson hastalarında olfaktör bulbus volüm ve olfaktör sulkus derinliğinin manyetik rezonans görüntüleme ile değerlendirilmesi. Kırıkkale Üni Tıp Fak Derg. 2019;21(1):22-27. doi:10.24938/kutfd.429018
  • Altmann J. Autoradiographic and histological studies of postnatal neurogenesis. IV. cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol. 1969;137(4):433-457.
  • Graziadei PPC, Graziadei GM. Neurogenesis and neuronregeneration in the olfactory system of mammals. III. deafferentation and reinnervation of the olfactory bulb following section of the fila olfactoria in rat. J Neurocytol. 1980;9(2):145-162.
  • Takahashi T, Ota M, Numata Y, et al. Relationships between the Fear of COVID-19 Scale and regional brain atrophy in mild cognitive impairment. Acta Neuropsychiatrica. 2022;34(3):153-162.
  • Rebsamen M, Friedli C, Radojewski P, et al. Multiple sclerosis as a model to investigate SARS-CoV-2 effect on brain atrophy. CNS Neurosci Ther. 2023;29(2):538-543. doi: 10.1111/cns.14050
  • Jobin B, Boller B, Frasnelli J. Volumetry of olfactory structures in mild cognitive impairment and Alzheimer’s disease: a systematic review and a meta‐analysis. Brain Sci. 2021;11(8):6-13. doi: 10.3390/brainsci11081010
  • Al-Otaibi M, Lessard-Beaudoin M, Castellano CA, et al. Volumetric MRI demonstrates atrophy of the olfactory cortex in AD. Curr Alzheimer Res. 2021;17(10):904-915.
  • Najt P, Richards HL, Fortune DG. Brain imaging in patients with COVID-19: a systematic review. Brain Behav Immun Health. 2021;16:100290. doi: 10.1016/j.bbih.2021.100290
  • Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18-22. doi: 10.1016/j.bbi.2020. 03.031
  • Lu Y, Li X, Geng D, et al. Cerebral micro-structural changes in COVID-19 patients–an MRI-based 3-month follow-up study. EClinicalMedicine. 2020;25:100484. doi: 10.1016/j.eclinm.2020.100484
  • Rahman A, Tabassum T, Araf Y, et al. Silent hypoxia in COVID-19: pathomechanism and possible management strategy. Mol Biol Rep. 2021;48(4):3863-3869. doi: 10.1007/s11033-021-06358-1
  • Ahmed M, Roy S, Iktidar MA, et al. Post-COVID-19 memory complaints: prevalence and associated factors. Neurología. 2022. doi: 10.1016/j.nrl.2022.03.007
  • Mahajan A, Mason GF. A sobering addition to the literature on COVID-19 and the brain. J Clin Invest. 2021;131(8):e148376. doi: 10.1172/JCI148376
  • Liu X, Yan W, Lu T, Han Y, Lu L. Longitudinal abnormalities in brain structure in COVID-19 patients. Neurosci Bull. 2022;38(12):1608-1612. doi: 10.1007/s12264-022-00913-x
  • Shan D, Li S, Xu R, et al. Post-COVID-19 human memory impairment: a PRISMA-based systematic review of evidence from brain imaging studies. Front Aging Neurosci. 2022;14:1077384. doi: 10.3389/fnagi.2022.1077384.
  • Cecchetti G, Agosta F, Canu E, et al. Cognitive, EEG, and MRI features of COVID-19 survivors: a 10-month study. J Neurol. 2022;269(7):3400-3412. doi: 10.1007/s00415-022-11047-5
  • Ermis U, Rust MI, Bungenberg J, et al. Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients. Neurol Res Pract. 2021;3(1):1-12. doi: 10.1186/s42466-021-00116-1
  • Hadad R, Khoury J, Stanger C, et al. Cognitive dysfunction following COVID-19 infection. J Neurovirol. 2022;28(3):430-437. doi: 10.1007/s13365-022-01079-y
  • Meyer PT, Hellwig S, Blazhenets G, et al. Molecular imaging findings on acute and long-term effects of COVID-19 on the brain: a systematic review. J Nucl Med. 2022;63(7):971-980. doi: 10.2967/jnumed.121.263085
  • Bungenberg J, Humkamp K, Hohenfeld C, et al. Long COVID-19: objectifying most self-reported neurological symptoms. Annal Clin Transl Neurol. 2022;9(2):141-154. doi: 10.1002/acn3.51496
  • Newhouse A, Kritzer MD, Eryilmaz H, et al. Neurocircuitry hypothesis and clinical experience treating neuropsychiatric symptoms of post acute sequelae of SARS-CoV-2 (PASC). J Acad Consult Liaison Psychiatry. 2022;63(6):619-627. doi: 10.1016/j.jaclp.2022. 08.007
  • Tian T, Wu J, Chen T, et al. Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations. JCI Insight. 2022;7(4):e155827. doi: 10.1172/jci.insight.155827
  • Fernández-Castañeda 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
  • Li C, Liu J, Lin J. et al. COVID-19 and risk of neurodegenerative disorders: a Mendelian randomization study. Transl Psychiatry. 2022;12(1):283. doi.org/10.1038/s41398-022-02052-3
  • Rahmati M, Yon DK, Lee SW, et al. New-onset neurodegenerative diseases as long-term sequelae of SARS-CoV-2 infection: a systematic review and meta-analysis. J Med Virol. 2023;95(7):e28909. doi: 10.1002/jmv.28909.
  • Leng A, Shah M, Ahmad SA, et al. Pathogenesis underlying neurological manifestations of long COVID syndrome and potential therapeutics. Cells. 2023;12(5):816. doi.org/10.3390/cells 12050816
There are 48 citations in total.

Details

Primary Language English
Subjects Central Nervous System
Journal Section Research Articles
Authors

Sinan Eliaçık 0000-0002-9415-0039

Mehmet Büyükşireci 0000-0002-9004-3105

Publication Date January 15, 2024
Submission Date November 6, 2023
Acceptance Date December 14, 2023
Published in Issue Year 2024 Volume: 6 Issue: 1

Cite

AMA Eliaçık S, Büyükşireci M. Asymptomatic COVID-19 and structural changes in the brain. Anatolian Curr Med J / ACMJ / acmj. January 2024;6(1):59-64. doi:10.38053/acmj.1386041

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