AccScience Publishing / AN / Volume 3 / Issue 1 / DOI: 10.36922/an.2200
Cite this article
Journal Browser
Volume | Year
News and Announcements
View All

Linkage between SARS-CoV-2 infection and neurodegenerative disorders: Review and current update

Amaan Javed* Anika Batra Mehak Singh Parnica Sarkar
Show Less
1 University College of Medical Sciences (University of Delhi), Dilshad Garden, Delhi, India
Advanced Neurology 2024, 3(1), 2200
Submitted: 7 November 2023 | Accepted: 9 January 2024 | Published: 14 March 2024
© 2024 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, followed by the Middle East respiratory syndrome coronavirus (MERS-CoV) that causes fatal illness in 2012, has made coronaviruses a public health concern. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection does not only affect the respiratory system but has also been observed to elicit neurological manifestations, with anosmia and ageusia being the most common, followed by headache, seizures, neuropathies, and encephalopathy. In addition to SARS-CoV and MERS-CoV which have been proven to be neuroinvasive, SARS-CoV-2 has been found to worsen preexisting long-term neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, apart from triggering the acute neurological symptoms. The association between COVID-19 and relatively rare neurodegenerative disorders such as amyotrophic lateral sclerosis and Huntington’s disease has yet to be corroborated due to limited significant data. Studies have shown that COVID-19 does not seem to exacerbate these disorders, and the severity of COVID-19-related disease and fatalities is not significantly higher in the affected patients than in the general population. However, increased complications have been reported among the patients in advanced stages of these diseases. Hence, it is imperative to conduct long-term, comprehensive investigations on the effects of SARS-CoV-2 on neurodegenerative disorders, with the ultimate aim of developing appropriate interventions. Studies involving larger cohorts of people of varying ages, disease duration, and ethnicity are urgently warranted.

Neurological sequelae
Neurodegenerative disorder
  1. COVID-Coronavirus Statistics-Worldometer. Available from: vignette [Last accessed on 2023 Nove 20].


  1. Pezzini A, Padovani A. Lifting the mask on neurological manifestations of COVID-19. Nat Rev Neurol. 2020;16(11):636- 644. doi: 10.1038/s41582-020-0398-3


  1. Dolatshahi M, Sabahi M, Aarabi MH. Pathophysiological clues to how the emergent SARS-CoV-2 can potentially increase the susceptibility to neurodegeneration. Mol Neurobiol. 2021;58(5):2379-2394. doi: 10.1007/s12035-020-02236-2


  1. Hu C, Chen C, Dong XP. Impact of COVID-19 pandemic on patients with neurodegenerative diseases. Front Aging Neurosci. 2021;13:664965. doi: 10.3389/FNAGI.2021.664965


  1. Kumar S, Veldhuis A, Malhotra T. Neuropsychiatric and cognitive sequelae of COVID-19. Front Psychol. 2021;12:577529. doi: 10.3389/fpsyg.2021.577529


  1. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141-154. doi: 10.1038/s41579-020-00459-7


  1. Montazersaheb S, Hosseiniyan Khatibi SM, Hejazi MS, et al. COVID-19 infection: An overview on cytokine storm and related interventions. Virol J. 2022;19(1):92. doi: 10.1186/S12985-022-01814-1
  2. Jarius S, Pache F, Körtvelyessy P, et al. Cerebrospinal fluid findings in COVID-19: A multicenter study of 150 lumbar punctures in 127 patients. J Neuroinflammation. 2022;19(1):19. doi: 10.1186/S12974-021-02339-0


  1. Elmakaty I, Ferih K, Karen O, et al. Clinical implications of COVID-19 presence in CSF: Systematic review of case reports. Cells. 2022;11(20):3212. doi: 10.3390/Cells11203212


  1. Veleri S. Neurotropism of SARS-CoV-2 and neurological diseases of the central nervous system in COVID-19 patients. Exp Brain Res. 2022;240(1):9-25. doi: 10.1007/S00221-021-06244-Z


  1. Batchu S, Diaz MJ, Tran JT, et al. Spatial mapping of genes implicated in SARS-CoV-2 neuroinvasion to dorsolateral prefrontal cortex gray matter. COVID. 2023;3(1):82. doi: 10.3390/COVID3010005


  1. Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A. 2020;117(21): 11727-11734. doi: 10.1073/pnas.2003138117


  1. Chen YT, Shao SC, Lai ECC, Hung MJ, Chen YC. Mortality rate of acute kidney injury in SARS, MERS, and COVID-19 infection: A systematic review and meta-analysis. Crit Care. 2020;24(1):439. doi: 10.1186/S13054-020-03134-8


  1. Islam MA, Cavestro C, Alam SS, Kundu S, Kamal MA, Reza F. Encephalitis in patients with COVID-19: A systematic evidence-based analysis. Cells. 2022;11(16):2575. doi: 10.3390/CELLS11162575


  1. Vengalil A, Nizamutdinov D, Su M, Huang JH. Mechanisms of SARS-CoV-2-induced encephalopathy and encephalitis in COVID-19 cases. Neurosci Insights. 2023;18:26331055231172522. doi: 10.1177/26331055231172522


  1. Steardo L, Steardo L, Zorec R, Verkhratsky A. Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19. Acta Physiol (Oxf). 2020;229(3):e13473. doi: 10.1111/apha.13473


  1. Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. 2021;78(6):682-683.

doi: 10.1001/jamapsychiatry.2021.0500


  1. Mingoti MED, Bertollo AG, Simões JLB, Francisco GR, Bagatini MD, Ignácio ZM. COVID-19, oxidative stress, and neuroinflammation in the depression route. J Mol Neurosci. 2022;72(6):1166-1181. doi: 10.1007/S12031-022-02004-Y


  1. Bowen DR, Pathak S, Nadar RM, et al. Oxidative stress and COVID-19-associated neuronal dysfunction: Mechanisms and therapeutic implications. Acta Biochim Biophys Sin (Shanghai). 2023;55(8):1153-1167. doi: 10.3724/ABBS.2023085


  1. Roldán-Santiago E, Benito-Berlinches A, Martínez-García L, et al. Severe acute respiratory syndrome coronavirus 2 spreads to lymph nodes and strongly expands CD4+ effector memory RA cells in a patient with mild coronavirus disease 2019. Clin Infect Dis. 2021;73(11):e3970-e3973. doi: 10.1093/CID/CIAA1422
  2. Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: A systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611-627. doi: 10.1016/S2215-0366(20)30203-0


  1. Schrag A, Taddei RN. Depression and anxiety in Parkinson’s disease. Int Rev Neurobiol. 2017;133:623-655. doi: 10.1016/BS.IRN.2017.05.024


  1. Salari M, Zali A, Ashrafi F, et al. Incidence of anxiety in Parkinson’s disease during the coronavirus disease (COVID-19) pandemic. Mov Disord. 2020;35(7):1095-1096. doi: 10.1002/MDS.28116


  1. Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T. The incidence of Parkinson’s disease: A systematic review and meta-analysis. Neuroepidemiology. 2016;46(4):292-300. doi: 10.1159/000445751


  1. Ascherio A, Schwarzschild MA. The epidemiology of Parkinson’s disease: Risk factors and prevention. Lancet Neurol. 2016;15(12):1257-1272. doi: 10.1016/S1474-4422(16)30230-7


  1. Kim CY, Alcalay RN. Genetic forms of Parkinson’s disease. Semin Neurol. 2017;37(2):135-146. doi: 10.1055/S-0037-1601567


  1. Sian J, Youdim MBH, Riederer P, Gerlach M. MPTP-induced Parkinsonian Syndrome. Philadelphia, PA: Lippincott- Raven; 1999.


  1. Beauchamp LC, Finkelstein DI, Bush AI, Evans AH, Barnham KJ. Parkinsonism as a third wave of the COVID-19 pandemic? J Parkinsons Dis. 2020;10(4):1343-1353. doi: 10.3233/JPD-202211


  1. Sulzer D, Antonini A, Leta V, et al. COVID-19 and possible links with Parkinson’s disease and parkinsonism: From bench to bedside. NPJ Parkinsons Dis. 2020;6(1):18. doi: 10.1038/s41531-020-00123-0


  1. Beauchamp LC, Dore V, Villemagne VL, et al. Using 18F-AV-133 VMAT2 PET imaging to monitor progressive nigrostriatal degeneration in Parkinson disease. Neurology. 2023;101(22):E2314-e2324. doi: 10.1212/WNL.0000000000207748


  1. Del Prete E, Francesconi A, Palermo G, et al. Prevalence and impact of COVID-19 in Parkinson’s disease: Evidence from a multi-center survey in Tuscany region. J Neurol. 2021;268(4):1179-1187. doi: 10.1007/S00415-020-10002-6


  1. Fasano A, Cereda E, Barichella M, et al. COVID-19 in Parkinson’s disease patients living in lombardy, Italy. Mov Disord. 2020;35(7):1089-1093. doi: 10.1002/MDS.28176


  1. Cilia R, Bonvegna S, Straccia G, et al. Effects of COVID-19 on Parkinson’s disease clinical features: A community-based case-control study. Mov Disord. 2020;35(8):1287-1292. doi: 10.1002/MDS.28170
  2. Leta V, Rodríguez-Violante M, Abundes A, et al. Parkinson’s disease and post-COVID-19 syndrome: The Parkinson’s long-COVID spectrum. Mov Disord. 2021;36(6):1287-1289. doi: 10.1002/MDS.28622


  1. Fasano A, Elia AE, Dallocchio C, et al. Predictors of COVID-19 outcome in Parkinson’s disease. Parkinsonism Relat Disord. 2020;78:134-137. doi: 10.1016/J.PARKRELDIS.2020.08.012


  1. Antonini A, Leta V, Teo J, Chaudhuri KR. Outcome of Parkinson’s disease patients affected by COVID‐19. Mov Disord. 2020;35(6):905-908. doi: 10.1002/MDS.28104


  1. Brown EG, Chahine LM, Goldman SM, et al. The effect of the COVID-19 pandemic on people with Parkinson’s disease. J Parkinsons Dis. 2020;10(4):1365-1377. doi: 10.3233/JPD-202249


  1. Zhang Q, Schultz JL, Aldridge GM, Simmering JE, Narayanan NS. Coronavirus disease 2019 case fatality and Parkinson’s disease. Mov Disord. 2020;35(11):1914-1915. doi: 10.1002/MDS.28325Volume X Issue X (2024) 9



  1. Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056. doi: 10.1038/NRDP.2015.56


  1. Armstrong RA. Risk factors for Alzheimer’s disease. Folia Neuropathol. 2019;57(2):87-105. doi: 10.5114/FN.2019.85929


  1. Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019;14:5541-5554. doi: 10.2147/IJN.S200490


  1. McQuaid C, Brady M, Deane R. SARS-CoV-2: Is there neuroinvasion? Fluids Barriers CNS. 2021;18(1):32. doi: 10.1186/S12987-021-00267-Y


  1. Matias-Guiu JA, Pytel V, Matias-Guiu J. Death rate due to COVID-19 in Alzheimer’s disease and frontotemporal dementia. J Alzheimers Dis. 2020;78(2):537-541. doi: 10.3233/JAD-200940


  1. Zhou Y, Xu J, Hou Y, et al. Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment. Alzheimers Res Ther. 2021;13(1):110. doi: 10.1186/s13195-021-00850-3


  1. Gao YD, Ding M, Dong X, et al. Risk factors for severe and critically ill COVID-19 patients: A review. Allergy. 2021;76(2):428-455. doi: 10.1111/ALL.14657


  1. Lim KH, Yang S, Kim SH, Joo JY. Elevation of ACE2 as a SARS-CoV-2 entry receptor gene expression in Alzheimer’s disease. J Infect. 2020;81(3):e33-e34. doi: 10.1016/J.JINF.2020.06.072


  1. Calsolaro V, Edison P. Neuroinflammation in Alzheimer’s disease: Current evidence and future directions. Alzheimers Dement. 2016;12(6):719-732. doi: 10.1016/J.JALZ.2016.02.010


  1. Copaescu A, Smibert O, Gibson A, Phillips EJ, Trubiano JA. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection. J Allergy Clin Immunol. 2020;146(3):518-534.e1. doi: 10.1016/J.JACI.2020.07.001


  1. Rahman MA, Islam K, Rahman S, Alamin M. Neurobiochemical cross-talk between COVID-19 and Alzheimer’s disease. Mol Neurobiol. 2020;58(3):1017-1023. doi: 10.1007/S12035-020-02177-W


  1. Ciaccio M, Lo Sasso B, Scazzone C, et al. COVID-19 and Alzheimer’s disease. Brain Sci. 2021;11(3):305. doi: 10.3390/BRAINSCI11030305


  1. Garcia-Revilla J, Deierborg T, Venero JL, Boza-Serrano A. Hyperinflammation and fibrosis in severe COVID-19 patients: Galectin-3, a target molecule to consider. Front Immunol. 2020;11:2069. doi: 10.3389/FIMMU.2020.02069


  1. Wang X, Zhang S, Lin F, Chu W, Yue S. Elevated galectin-3 levels in the serum of patients with Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2015;30(8):729-732. doi: 10.1177/1533317513495107


  1. N Hwang JM, Kim JH, Park JS, Chang MC, Park D. Neurological diseases as mortality predictive factors for patients with COVID-19: A retrospective cohort study. Neurol Sci. 2020;41(9):2317-2324. doi: 10.1007/S10072-020-04541-Z


  1. Li J, Long X, Huang H, et al. Resilience of Alzheimer’s disease to COVID-19. J Alzheimers Dis. 2020;77(1):67-73. doi: 10.3233/JAD-200649


  1. Vaz M, Silvestre S. Alzheimer’s disease: Recent treatment strategies. Eur J Pharmacol. 2020;887:173554. doi: 10.1016/J.EJPHAR.2020.173554


  1. Gowayed MA, Refaat R, Ahmed WM, El-Abhar HS. Effect of galantamine on adjuvant-induced arthritis in rats. Eur J Pharmacol. 2015;764:547-553. doi: 10.1016/J.EJPHAR.2015.07.038


  1. Gil R, Arroyo-Anlló EM. Alzheimer’s disease and face masks in times of COVID-19. J Alzheimers Dis. 2021;79(1):9-14. doi: 10.3233/JAD-201233


  1. Kobayashi R, Hayashi H, Kawakatsu S, et al. Recognition of the coronavirus disease 2019 pandemic and face mask wearing in patients with Alzheimer’s disease: An investigation at a medical centre for dementia in Japan. Psychogeriatrics. 2020;20(6):923-925. doi: 10.1111/psyg.12617



  1. Gan J, Liu S, Wu H, et al. The impact of the COVID-19 pandemic on Alzheimer’s disease and other dementias. Front Psychiatry. 2021;12:703481. doi: 10.3389/fpsyt.2021.703481


  1. El Haj M, Altintas E, Chapelet G, Kapogiannis D, Gallouj K. High depression and anxiety in people with Alzheimer’s disease living in retirement homes during the covid-19 crisis. Psychiatry Res. 2020;291:113294. doi: 10.1016/J.PSYCHRES.2020.113294


  1. Boutoleau-Bretonnière C, Pouclet-Courtemanche H, Gillet A, et al. Impact of confinement on the burden of caregivers of patients with the behavioral variant of frontotemporal dementia and Alzheimer disease during the COVID-19 crisis in France. Dement Geriatr Cogn Dis Extra. 2020;10(3): 127-134.Volume X Issue X (2024) 10 10.1159/000511416


  1. Trifan G, Goldenberg FD, Caprio FZ, et al. Characteristics of a diverse cohort of stroke patients with SARS-CoV-2 and outcome by sex. J Stroke Cerebrovasc Dis. 2020;29(11):105314. doi: 10.1016/J.JSTROKECEREBROVASDIS.2020.105314


  1. Zhang S, Zhang J, Wang C, et al. COVID-19 and ischemic stroke: Mechanisms of hypercoagulability (review). Int J Mol Med. 2021;47(3):21. doi: 10.3892/IJMM.2021.4854


  1. Imaeda S, Kabata H, Shiraishi Y, et al. Left ventricular thrombus with COVID-19 complication in a patient with dilated cardiomyopathy. CJC Open. 2021;3(1):124-126. doi: 10.1016/J.CJCO.2020.09.014


  1. Shchukin IA, Fidler MS, Koltsov IA, Suvorov AY. COVID-19-associated stroke. Neurosci Behav Physiol. 2022;52(5):649-656. doi: 10.1007/S11055-022-01291-7


  1. Wang A, Mandigo GK, Yim PD, Meyers PM, Lavine SD. Stroke and mechanical thrombectomy in patients with COVID-19: Technical observations and patient characteristics. J Neurointerv Surg. 2020;12(7):648-653. doi: 10.1136/NEURINTSURG-2020-016220


  1. Vogrig A, Gigli GL, Bnà C, Morassi M. Stroke in patients with COVID-19: Clinical and neuroimaging characteristics. Neurosci Lett. 2021;743:135564. doi: 10.1016/J.NEULET.2020.135564


  1. Wang H, Tang X, Fan H, et al. Potential mechanisms of hemorrhagic stroke in elderly COVID-19 patients. Aging (Albany NY). 2020;12(11):10022-10034. doi: 10.18632/AGING.103335


  1. Dogra S, Jain R, Cao M, et al. Hemorrhagic stroke and anticoagulation in COVID-19. J Stroke Cerebrovasc Dis. 2020;29(8):104984. doi: 10.1016/J.JSTROKECEREBROVASDIS.2020.104984Volume X Issue X (2024) 11
Conflict of interest
The authors declare no conflicts of interest.
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing