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Impact of COVID-19 on central nervous system biomarkers: A comparative analysis with multiple sclerosis and healthy controls in Erbil city, KRG, Iraq

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Research Paper 12/05/2024
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Impact of COVID-19 on central nervous system biomarkers: A comparative analysis with multiple sclerosis and healthy controls in Erbil city, KRG, Iraq

Daldar Fares Jeejo, Mayada Noori Iqbal, Nisreen Sherif Alyasiri
Int. J. Biosci.24( 5), 238-252, May 2024.
Certificate: IJB 2024 [Generate Certificate]
Key: BiomarkersCOVID-19Glial fibrillary acidic proteinMultiple sclerosisNeurofilament light chainNeuron-specific enolase

Abstract

The neurological implications of COVID-19 are becoming increasingly documented, Elevated serum biomarkers Neuron-Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), and Neurofilament Light Chain (NfL) show a strong association with neurological injury in both COVID-19 and Multiple Sclerosis (MS) patients. However, the use of biomarkers in the diagnosis and progression of COVID-19 and Multiple Sclerosis (MS) in the Kurdistan Region of Iraq (KRG) remains understudied. This investigation aims to assess the levels of GFAP, NSE, and NfL in COVID-19 and MS patients and compare them with healthy controls to establish their potential utility as biomarkers. Levels of Serum NSE, GFAP, and NfL were calculated in 91 COVID-19 patients, 29 MS patients, and 50 healthy controls using ELISA tests. To evaluate the differences between groups, statistical analysis was used, which included the application of the Kruskal-Walli’s test. NfL levels were noticeably greater in MS patients, while COVID-19 patients had significantly higher levels of GFAP and NSE than controls. There was a correlation between the severity of COVID-19 and elevated biomarker levels. According to the study’s findings, NSE and GFAP are markedly raised in COVID-19 patients, suggesting that they could be used as biomarkers for neurological involvement. Likewise, NfL levels were markedly increased in MS patients, highlighting its function as a biomarker for injury to the neuroaxon. Further research is recommended to corroborate these findings in a larger population and to explore the predictive value of these biomarkers for clinical outcomes. It is also recommended to extend interdisciplinary research to understand the pathophysiological mechanisms driving these biomarker changes.

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Abdelhak A, Huss A, Kassubek J, Tumani H, Otto M. 2019. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Sci Rep. 8(1), 14798. DOI: 10.1038/s41598-018-33158-8.

Al-Sarray AM, Shareef RH. 2022. Awareness of Healthcare Providers About COVID-19 Vaccinations in Karbala City. Journal of Techniques 4(Special Issue), 91-96. https://doi.org/10.51173/jt.v4i33.654,

Arneth B, Kraus J. 2022. Laboratory biomarkers of Multiple Sclerosis (MS). Clin Biochem 99, 1-8. https://doi.org/10.1016/j.clinbiochem.2021.10.004.

Asfahan S, Deokar K, Dutt N, Niwas R, Jain P, Agarwal M. 2020. Extrapolation of mortality in COVID-19: exploring the role of age, sex, co-morbidities and health-care related occupation. Monaldi Arch Chest Dis. 90(2).

Barzegar M, Sindarreh S, Manteghinejad A, Javanmard SH, Shaygannejad V, Nasirian M. 2023. Multiple sclerosis is associated with worse COVID-19 outcomes compared to the general population: A population-based study. Mult Scler Relat Disord. 79, 104947. https://doi.org/10.1016/j.msard.2023.104947.

Bittner S, Oh J, Havrdová EK. 2021. The potential of serum neurofilament as biomarker for multiple sclerosis. Brain. 144(10), 2954-2963. DOI: 10.1093/brain/awab241.

Bose P. 2023. Are plasma levels of axonal damage and neuronal degeneration makers altered in COVID-19 patients without major neurological manifestations? News-Medical. Net. 2023 Feb 3. Available from: https://www.news-medical.net/news/20230203/

Buck D, Hemmer B. 2014. Biomarkers of treatment response in multiple sclerosis. Expert Rev Neurother.14(2), 165-72. DOI: 10.1586/14737175.2014.874289.

Carethers JM. 2021. Insights into disparities observed with COVID-19. J Intern Med. 289(4), 463-473. https://doi.org/10.1111/joim.13199.

Conway SE, Healy BC, Zurawski J, Severson C, Kaplan T, Stazzone L. 2022. COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders. Mult Scler Relat Disord. 63, 103946. DOI: 10.1016/j.msard.2022.103946.

Czeiter E, Amrein K, Gravesteijn BY. 2020. Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study. EBioMedicine. 56, 102785. DOI: 10.1016/j.ebiom.2020.102785.

Dadas A, Washington J, Diaz-Arrastia R, Janigro D. 2018. Biomarkers in traumatic brain injury (TBI): a review. Neuropsychiatr Dis Treat., 14:2989-3000. DOI: 10.2147/NDT.S125620.

DeKosky ST, Kochanek PM, Valadka AB, Clark RSB, Chou SH-Y, Au AK, 2021. Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients. J Neurotrauma. 38(1), 1. DOI: 10.1089/neu.2020.7332.

Dondaine T, Ruthmann F, Vuotto F, Carton L, Gelé P, Faure K. 2022. Long-term cognitive impairments following COVID-19: a possible impact of hypoxia. J Neurol. 269(8), 3982-3989. DOI: 10.1007/s00415-022-11077-z.

Farshbafnadi M, Kamali Zonouzi S, Sabahi M, Dolatshahi M, Aarabi MH. 2021. Aging & COVID-19 susceptibility, disease severity, and clinical outcomes: The role of entangled risk factors. Exp Gerontol. 154, 111507. DOI: 10.1016/j.exger.2021.111507.

Fernandes de Souza WD, Fonseca DMD, Sartori A. 2023. COVID-19 and Multiple Sclerosis: A Complex Relationship Possibly Aggravated by Low Vitamin D Levels. Cells. 12(5), 684. DOI: 10.3390/cells12050684.

Forooghian F, Cheung RK, Smith WC, O’Connor P, Dosch HM. 2007. Enolase and arrestin are novel nonmyelin autoantigens in multiple sclerosis. J Clin Immunol. 27(4), 388-96. DOI: 10.1007/s10875-007-9091-1.

Gelderblom M, Daehn T, Schattling B, Ludewig P, Bernreuther C, Arunachalam P. 2013. Plasma levels of neuron specific enolase quantify the extent of neuronal injury in murine models of ischemic stroke and multiple sclerosis. Neurobiol Dis. 59, 177-82. DOI: 10.1016/j.nbd.2013.07.017.

Gill J, Latour L, Diaz-Arrastia R. 2018. Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI. Neurology. 91(15), e1385-e1389. DOI: 10.1212/WNL.0000000000006321.

Giovannini G, Bedin R, Ferraro D, Vaudano AE, Mandrioli J, Meletti S. 2022. Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus. Epilepsia. 63(1), e23-e29. DOI: 10.1111/epi.17132.

Gyang T, Rempe T. 2021. The State of Biomarkers in Multiple Sclerosis. NeurologyLive. 4(6). Available from: https://www.neurologylive.com/view/the-state-of-biomarkers-in-multiple-sclerosis.

Haines JD, Inglese M, Casaccia P. 2011. Axonal damage in multiple sclerosis. Mt Sinai J Med. 78(2), 231-43. DOI: 10.1002/msj.20246.

Hay M, Ryan L, Huentelman M, Konhilas J, Hoyer-Kimura C, Beach TG. 2021. Serum Neurofilament Light is elevated in COVID-19 Positive Adults in the ICU and is associated with Co-Morbid Cardiovascular Disease, Neurological Complications, and Acuity of Illness. Cardiol Cardiovasc Med. 5(5), 551-565. DOI: 10.26502/fccm.92920221.

Heidari A, Rezaei N. 2023. The role of neurofilament light chain in COVID‐19: A potential prognostic biomarker. Acta Neurobiol Exp (Wars). 83(2), 111-126. DOI: 10.55782/ane-2023-011.

Herrera-Esposito D, de Los Campos G. 2022. Age-specific rate of severe and critical SARS-CoV-2 infections estimated with multi-country seroprevalence studies. BMC Infect Dis. 22(1), 311. DOI: 10.1186/s12879-022-07262-0.

Högel H, Rissanen E, Barro C. 2020. Serum glial fibrillary acidic protein correlates with multiple sclerosis disease severity. Mult Scler J. 26(2), 210-219. DOI: 10.1177/1352458518819380.

Iqbal A, Iqbal K, Ali SA, Azim D, Farid E, Baig MD. 2021. The COVID-19 sequelae: a cross-sectional evaluation of post-recovery symptoms and the need for rehabilitation of COVID-19 survivors. Cureus.  13(2).

Jin JM, Bai P, He W, Wu F, Liu XF, Han DM. 2020. Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Front Public Health. 8, 152. DOI: 10.3389/fpubh.2020.00152.

Khatoon F, Prasad K, Kumar V. 2022. COVID-19 associated nervous system manifestations. Sleep Med. 91, 231-236. DOI: 10.1016/j.sleep.2021.07.005.

Koch MW, George S, Wall W, Yong VW, Metz LM. 2015. Serum NSE level and disability progression in multiple sclerosis. J Neurol Sci. 350(1-2), 46-50. DOI: 10.1016/j.jns.2015.02.009.

Kokkoris S, Stamataki E, Emmanouil G, Psachoulia C, Ntaidou T, Maragouti A. 2022. Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study. eNeurologicalSci. 29:100434. https://doi.org/10.1016/j.ensci.2022.100434

Kuhle J, Kropshofer H, Haering DA. 2019. Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology. 92(10), e1007-e1015. DOI: 10.1212/WNL.0000000000007032.

Kulbe JR, Geddes JW. 2016. Current status of fluid biomarkers in mild traumatic brain injury. Exp Neurol. 275(Pt 3):334-52. DOI: 10.1016/j.expneurol.2015.05.004.

La Vignera S, Cannarella R, Condorelli RA, Torre F, Aversa A, Calogero AE. 2020. Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D. Int J Mol Sci. 21(8), E2948. https://doi.org/10.3390/ijms21082948.

Leister I, Altendorfer B, Maier D, Mach O, Wutte C, Grillhösl A. 2021. Serum Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein Are Related to the Neurological Impairment and Spinal Edema after Traumatic Spinal Cord Injury. J Neurotrauma. 38(24), 3431-3439. DOI: 10.1089/neu.2021.0264.

Maury A, Lyoubi A, Peiffer-Smadja N, de Broucker T, Meppiel E. 2021. Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians. Rev Neurol (Paris). 177(1-2), 51-64. https://doi.org/10.1016/j.neurol.2020.10.001.

Mendoza DA, López KD, Echeverri RA, Pastor L, Rueda S, Fernández LL. 2020. Utility of biomarkers in traumatic brain injury: a narrative review. Colombian Journal of Anesthesiology 48(3), 155-161. DOI: 10.1097/CJ9.0000000000000165.

Momtazmanesh S, Shobeiri P, Saghazadeh A, Teunissen CE, Burman J, Szalardy L. 2021. Neuronal and glial CSF biomarkers in multiple sclerosis: a systematic review and meta-analysis. Rev Neurosci. 32(6), 573-595. https://doi.org/10.1515/revneuro-2020-0145.

Moreno-Torres I, Meca Lallana V, Costa-Frossard L, Oreja-Guevara C, Aguirre C, Alba Suárez EM. 2021. Risk and outcomes of COVID-19 in patients with multiple sclerosis. Eur J Neurol. 28(11), 3712-3721. DOI: 10.1111/ene.14990.

Morillo-González J, Hernández-Huerta D, Guillama-Henríquez A, Correa-Palacio A, Pereira-Nogueira P. 2020. Beyond the Respiratory System: A Case Report Highlighting the Impact of COVID-19 in Mental Illness and Its Physical Consequences. J Clin Psychiatry 81(4), 317.

Nazzal AG, Sabbar AG. 2022. Estimation of Some Biomarkers in Recovered COVID19 Patients. Journal of Techniques  4(special issue), 21-27. https://doi.org/10.51173/jt.v4i33.587.

Needham EJ, Ren AL, Digby RJ, Norton EJ, Ebrahimi S, Outtrim JG. 2022. Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses. Brain. 145(11), 4097-4107. DOI: 10.1093/brain/awac321.

Ning L, Wang B. 2022. Neurofilament light chain in blood as a diagnostic and predictive biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One. 17(9), e0274565. DOI: 10.1371/journal.pone.0274565.

Nishimura K, Cordeiro JG, Ahmed AI. 2022. Advances in Traumatic Brain Injury Biomarkers. Cureus. 14(4), e23804. DOI:10.7759/cureus.23804.

Otani K, Fukushima H, Matsuishi K. 2023. COVID-19 delirium and encephalopathy: Pathophysiology assumed in the first 3 years of the ongoing pandemic. Brain Disord. 10, 100074. DOI: 10.1016/j.dscb.2023.100074.

Pivonello R, Auriemma RS, Pivonello C, Isidori AM, Corona G, Colao A, Millar RP. 2021. Sex Disparities in COVID-19 Severity and Outcome: Are Men Weaker or Women Stronger? Neuroendocrinology 111(11), 1066-1085. DOI: 10.1159/000513346.

Richter D, Faissner S, Bartig D. 2021. Multiple sclerosis is not associated with an increased risk for severe COVID-19: a nationwide retrospective cross-sectional study from Germany. Neurol Res Pract. 3, 42. https://doi.org/10.1186/s42466-021-00143-y.

Rodat T, Cunningham JI, Morrow CF, Johnston KD, Buchanan KD. 1994. Serum neurone-specific enolase concentrations in patients with neurological disorders. Clin Chim Acta. 230(2), 117-24. https://doi.org/10.1016/0009-8981(94)90264-x.

Sahin BE, Celikbilek A, Kocak Y, Ilanbey B, Saltoglu GT, Konar NM, Hizmali L. 2023. Neurological symptoms and neuronal damage markers in acute COVID-19: Is there a correlation? A pilot study. J Med Virol. 95(1). DOI: 10.1002/jmv.28240.

Sahin BE, Celikbilek A, Kocak Y, Saltoglu GT, Konar NM, Hizmali L. 2022. Plasma biomarkers of brain injury in COVID-19 patients with neurological symptoms. J Neurological Sci., 17. Available from: https://doi.org/10.1016/j.jns.2022.120324.

Saleki K, Banazadeh M, Miri NS, Azadmehr A. 2022. Triangle of cytokine storm, central nervous system involvement, and viral infection in COVID-19: the role of sFasL and neuropilin-1. Rev Neurosci., 33(2), 147-160. https://doi.org/10.1515/revneuro-2021-0047.

Saraste M, Bezukladova S, Matilainen M. 2021. Increased serum glial fibrillary acidic protein associates with microstructural white matter damage in multiple sclerosis: GFAP and DTI. Mult Scler Relat Disord. 50, 102810. DOI: 10.1016/j.msard.2021.102810.

Sarıoğlu E, Sarıaltın SY, Çoban T. 2023. Neurological complications and effects of COVID-19: Symptoms and conceivable mechanisms. Brain Hemorrhages. 4(3), 154-173. https://doi.org/10.1016/j.hest.2023.02.001.

Schwartz CE, Rapkin BD, Bonavita S, Bossa M, Buscarinu MC, Grasso MG. 2022. The impact of COVID-19 on people with multiple sclerosis: A comparison of Italian and United States cohorts. Mult Scler Relat Disord. 63, 103888. https://doi.org/10.1016/j.msard.2022.103888.

Serafeim K, Anagnostouli M. 2013. Biomarkers in Multiple Sclerosis: An Up-to-Date Overview. Mult Scler Int. 2013, 340508. DOI: 10.1155/2013/340508.

Sharquie IK, Gawwam GA, Abdullah SF. 2020. Serum Glial Fibrillary Acidic Protein: A Surrogate Marker of the Activity of Multiple Sclerosis. Medeni Med J. 35(3), 212-218. DOI: 10.5222/MMJ.2020.48265.

Siliezar J. 2022. GenderSci Lab finds social factors, not biological difference between sexes, play biggest role by far. Harvard Gazette. 2022 Jan 20. Available from: https://news.harvard.edu/gazette/story/2022/01/.

Silva RC, da Rosa MM, Leão HI, Silva EDL, Ferreira NT, Albuquerque APB. 2023. Brain damage serum biomarkers induced by COVID-19 in patients from northeast Brazil. J Neurovirol. 29(2), 180-186. DOI: 10.1007/s13365-023-01119-1.

Sormani MP, Schiavetti I, Carmisciano L, Cordioli C, Filippi M, Radaelli M. 2022. COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context. Neurol Neuroimmunol Neuroinflamm. 9(1), e1105. https://doi.org/10.1212/NXI.0000000000001105.

Spudich S, Nath A. 2022. Nervous system consequences of COVID-19. Science. 375(6578), 267-269. DOI: 10.1126/science.abm2052.

Sukocheva OA, Maksoud R, Beeraka NM, Madhunapantula SV, Sinelnikov M, Nikolenko VN. 2022. Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. J Adv Res. 40, 179-196. DOI: 10.1016/j.jare.2021.11.013.

Sun M, Liu N, Xie Q. 2021. A candidate biomarker of glial fibrillary acidic protein in CSF and blood in differentiating multiple sclerosis and its subtypes: A systematic review and meta-analysis. Mult Scler Relat Disord. 51, 102870. DOI: 10.1016/j.msard.2021.102870.

Telser J, Grossmann K, Weideli OC, Hillmann D, Aeschbacher S, Wohlwend N. 2023. The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID – results from the prospective population-based COVI-GAPP study. medRxiv. 15:2023.02.15.23285972. https://doi.org/10.1101/2023.02.15.23285972.

Thepmankorn P, Bach J, Lasfar A, Zhao X, Souayah S, Chong ZZ, Souayah N. 2021. Cytokine storm induced by SARS-CoV-2 infection: The spectrum of its neurological manifestations. Cytokine. 138, 155404.

Turke PW. 2020. Five reasons COVID-19 is less severe in younger age-groups. Evol Med Public Health. 9(1), 113-117. DOI: 10.1093/emph/eoaa050.

Verde F, Milone I, Bulgarelli I, Peverelli S, Colombrita C, Maranzano A. 2022. Serum neurofilament light chain levels in Covid-19 patients without major neurological manifestations. J Neurol. 269(11), 5691-5701. DOI: 10.1007/s00415-022-11233-5.

Virhammar J, Nääs A, Fällmar D, Cunningham JL, Klang A, Ashton NJ. 2021. Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity. Eur J Neurol. 28(10), 3324-3331. DOI: 10.1111/ene.14703.

Vrettou CS, Vassiliou AG, Pratikaki M, Keskinidou C, Tsipilis S, Gallos P. 2022. Comparative evaluation and prognostic utility of neuronal injury biomarkers in covid-19 patients: a prospective study. Shock 58(6), 507-13.

Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, Manley GT. 2018. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 18(2), 165-180. DOI: 10.1080/14737159.2018.1428089.

Wang S, Zha X, Zhu X. 2018. Metabolic syndrome and its components with neuron-specific enolase: a cross-sectional study in large health check-up population in China. BMJ Open. 8(4), e020899. DOI: 10.1136/bmjopen-2017-020899.

Wilde EA, Wanner IB, Kenney K, Gill J, Stone JR, Disner S. 2022. A Framework to Advance Biomarker Development in the Diagnosis, Outcome Prediction, and Treatment of Traumatic Brain Injury. J Neurotrauma 39(7-8). https://doi.org/10.1089/neu.2021.0099.

Yang J, Hamade M, Wu Q, Wang Q, Axtell R, Giri S, Mao-Draayer Y. 2022. Current and Future Biomarkers in Multiple Sclerosis. Int J Mol Sci. 23(11), 5877. DOI: 10.3390/ijms23115877.

Youssef P, Hughes L, Kim WS, Halliday GM, Lewis SJG, Cooper A. 2023. Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson’s disease biomarkers using multiplexed single molecule counting. Sci Rep. 13(1), 5217. DOI: 10.1038/s41598-023-32480-0.

Zhang J, Puvenna V, Janigro D. 2016. Biomarkers of Traumatic Brain Injury and Their Relationship to Pathology. In: Laskowitz D, Grant G, editors. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Chapter 12. Available from: https://www.ncbi.nlm.nih.gov/books/NBK326724/.

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