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Long-Term COVID-19 Neurological Symptoms: A Review of Epidemiology, Pathophysiology, and Treatment


  • Jasleen Grewal Western Sierra Collegiate Academy



COVID-19, Neuroscience, Epidemiology, Pathophysiology


The World Health Organization (WHO) announced the discovery of a novel coronavirus, called COVID-19, in Wuhan, a central city in China, on January 10, 2020. Additionally, COVID-19 has been known to lead to many neurological dysfunctions including anosmia, dysgeusia, stroke, anxiety, depression, and memory loss/brain fog. Here we highlight neurological complications related to COVID-19 infection and cover epidemiology, current understood pathophysiology, and treatment options available. 


Abbasi, Jennifer. “Even Mild COVID-19 May Change the Brain.” Jama Network,

Alnefeesi Y, Siegel A, Lui LMW, Teopiz KM, Ho RCM, Lee Y, Nasri F, Gill H, Lin K, Cao B, Rosenblat JD, McIntyre RS. Impact of SARS-CoV-2 Infection on Cognitive Function: A Systematic Review. Front Psychiatry. 2021 Feb 10;11:621773. doi: 10.3389/fpsyt.2020.621773. PMID: 33643083; PMCID: PMC7902710.

Beyrouti R, Adams ME, Benjamin L, Cohen H, Farmer SF, Goh YY, Humphries F, Jäger HR, Losseff NA, Perry RJ, Shah S, Simister RJ, Turner D, Chandratheva A, Werring DJ. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry. 2020 Aug;91(8):889-891. doi: 10.1136/jnnp-2020-323586. Epub 2020 Apr 30. PMID: 32354768; PMCID: PMC7231545.

Bilinska K, Butowt R. Anosmia in COVID-19: A Bumpy Road to Establishing a Cellular Mechanism. ACS Chem Neurosci. 2020 Aug 5;11(15):2152-2155. doi: 10.1021/acschemneuro.0c00406. Epub 2020 Jul 16. PMID: 32673476; PMCID: PMC7467568.

Birsel, Robert, and Sayantani Ghosh. “Covid-19 Can Cause Brain Shrinkage, Memory Loss - StudySayantani .” Reuters, Thomson Reuters, 8 Mar. 2022,

Boldrini M, Canoll PD, Klein RS. How COVID-19 Affects the Brain. JAMA Psychiatry. 2021 Jun 1;78(6):682-683. doi: 10.1001/jamapsychiatry.2021.0500. PMID: 33769431.

Borch L, Holm M, Knudsen M, Ellermann-Eriksen S, Hagstroem S. Long COVID symptoms and duration in SARS-CoV-2 positive children - a nationwide cohort study. Eur J Pediatr. 2022 Apr;181(4):1597-1607. doi: 10.1007/s00431-021-04345-z. Epub 2022 Jan 9. PMID: 35000003; PMCID: PMC8742700.

Daly M, Robinson E. Depression and anxiety during COVID-19. Lancet. 2022 Feb 5;399(10324):518. doi: 10.1016/S0140-6736(22)00187-8. PMID: 35123689; PMCID: PMC8813060.

Deng J, Zhou F, Hou W, Silver Z, Wong CY, Chang O, Huang E, Zuo QK. The prevalence of depression, anxiety, and sleep disturbances in COVID-19 patients: a meta-analysis. Ann N Y Acad Sci. 2021 Feb;1486(1):90-111. doi: 10.1111/nyas.14506. Epub 2020 Oct 2. PMID: 33009668; PMCID: PMC7675607.

Eliezer M, Hamel AL, Houdart E, Herman P, Housset J, Jourdaine C, Eloit C, Verillaud B, Hautefort C. Loss of smell in patients with COVID-19: MRI data reveal a transient edema of the olfactory clefts. Neurology. 2020 Dec 8;95(23):e3145-e3152. doi: 10.1212/WNL.0000000000010806. Epub 2020 Sep 11. PMID: 32917809.

Fernández-de-Las-Peñas C, Gómez-Mayordomo V, Cuadrado ML, Palacios-Ceña D, Florencio LL, Guerrero AL, García-Azorín D, Hernández-Barrera V, Arendt-Nielsen L. The presence of headache at onset in SARS-CoV-2 infection is associated with long-term post-COVID headache and fatigue: A case-control study. Cephalalgia. 2021 Nov;41(13):1332-1341. doi: 10.1177/03331024211020404. Epub 2021 Jun 16. PMID: 34134526; PMCID: PMC8212025.

Forte G, Favieri F, Casagrande M. Heart Rate Variability and Cognitive Function: A Systematic Review. Front Neurosci. 2019 Jul 9;13:710. doi: 10.3389/fnins.2019.00710. PMID: 31354419; PMCID: PMC6637318.

Galluzzi F, Rossi V, Bosetti C, Garavello W. Risk Factors for Olfactory and Gustatory Dysfunctions in Patients with SARS-CoV-2 Infection. Neuroepidemiology. 2021;55(2):154-161. doi: 10.1159/000514888. Epub 2021 Apr 1. PMID: 33794531.

Graham EL, Clark JR, Orban ZS, Lim PH, Szymanski AL, Taylor C, DiBiase RM, Jia DT, Balabanov R, Ho SU, Batra A, Liotta EM, Koralnik IJ. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers". Ann Clin Transl Neurol. 2021 May;8(5):1073-1085. doi: 10.1002/acn3.51350. Epub 2021 Mar 30. PMID: 33755344; PMCID: PMC8108421.

Guo, Panyuan, et al. “COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication from the COVID and Cognition Study.” Frontiers, Frontiers, 1 Jan. 1AD,

Havervall S, Rosell A, Phillipson M, Mangsbo SM, Nilsson P, Hober S, Thålin C. Symptoms and Functional Impairment Assessed 8 Months After Mild COVID-19 Among Health Care Workers. JAMA. 2021 May 18;325(19):2015-2016. doi: 10.1001/jama.2021.5612. PMID: 33825846; PMCID: PMC8027932.

Katella, Kathy. “Comparing the COVID-19 Vaccines: How Are They Different?” Yale Medicine, Yale Medicine, 6 Jan. 2023,

Khani E, Khiali S, Beheshtirouy S, Entezari-Maleki T. Potential pharmacologic treatments for COVID-19 smell and taste loss: A comprehensive review. Eur J Pharmacol. 2021 Dec 5;912:174582. doi: 10.1016/j.ejphar.2021.174582. Epub 2021 Oct 19. PMID: 34678243; PMCID: PMC8524700.

“Asymptomatic and Presymptomatic SARS-COV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility - King County, Washington, March 2020.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 2 Apr. 2020,

Klimek L, Hagemann J, Döge J, Freudelsperger L, Cuevas M, Klimek F, Hummel T. Olfactory and gustatory disorders in COVID-19. Allergo J Int. 2022 Jun 20:1-8. doi: 10.1007/s40629-022-00216-7. Epub ahead of print. PMID: 35755859; PMCID: PMC9208356.

Koyama S, Kondo K, Ueha R, Kashiwadani H, Heinbockel T. Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia. Int J Mol Sci. 2021 Aug 18;22(16):8912. doi: 10.3390/ijms22168912. PMID: 34445619; PMCID: PMC8396277.

Laurendon T, Radulesco T, Mugnier J, Gérault M, Chagnaud C, El Ahmadi AA, Varoquaux A. Bilateral transient olfactory bulb edema during COVID-19-related anosmia. Neurology. 2020 Aug 4;95(5):224-225. doi: 10.1212/WNL.0000000000009850. Epub 2020 May 22. PMID: 32444492.

Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020 Jun;92(6):552-555. doi: 10.1002/jmv.25728. Epub 2020 Mar 11. PMID: 32104915; PMCID: PMC7228394.

Lo JC, Chong PL, Ganesan S, Leong RL, Chee MW. Sleep deprivation increases formation of false memory. J Sleep Res. 2016 Dec;25(6):673-682. doi: 10.1111/jsr.12436. Epub 2016 Jul 5. PMID: 27381857; PMCID: PMC5324644.

Loewen, Dr. Jaycie. “Memory Loss after COVID-19: Causes and Treatment.” Home, 9 Sept. 2022,

Loewen, Dr. Jaycie. “Yes, Long Covid Can Cause Pots and Dysautonomia.” Cognitive FX, 8 Dec. 2022,

Mahmoud MM, Abuohashish HM, Khairy DA, Bugshan AS, Khan AM, Moothedath MM. Pathogenesis of dysgeusia in COVID-19 patients: a scoping review. Eur Rev Med Pharmacol Sci. 2021 Jan;25(2):1114-1134. doi: 10.26355/eurrev_202101_24683. PMID: 33577069.

Najafloo R, Majidi J, Asghari A, Aleemardani M, Kamrava SK, Simorgh S, Seifalian A, Bagher Z, Seifalian AM. Mechanism of Anosmia Caused by Symptoms of COVID-19 and Emerging Treatments. ACS Chem Neurosci. 2021 Oct 20;12(20):3795-3805. doi: 10.1021/acschemneuro.1c00477. Epub 2021 Oct 5. PMID: 34609841; PMCID: PMC8507153.

Paderno A, Mattavelli D, Rampinelli V, Grammatica A, Raffetti E, Tomasoni M, Gualtieri T, Taboni S, Zorzi S, Del Bon F, Lombardi D, Deganello A, Redaelli De Zinis LO, Schreiber A. Olfactory and Gustatory Outcomes in COVID-19: A Prospective Evaluation in Nonhospitalized Subjects. Otolaryngol Head Neck Surg. 2020 Dec;163(6):1144-1149. doi: 10.1177/0194599820939538. Epub 2020 Jun 30. PMID: 32600175; PMCID: PMC7331108.

Premraj L, Kannapadi NV, Briggs J, Seal SM, Battaglini D, Fanning J, Suen J, Robba C, Fraser J, Cho SM. Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. J Neurol Sci. 2022 Mar 15;434:120162. doi: 10.1016/j.jns.2022.120162. Epub 2022 Jan 29. PMID: 35121209; PMCID: PMC8798975.

Rana BK, Panizzon MS, Franz CE, Spoon KM, Jacobson KC, Xian H, Ancoli-Israel S, Lyons M, Kremen WS. Association of Sleep Quality on Memory-Related Executive Functions in Middle Age. J Int Neuropsychol Soc. 2018 Jan;24(1):67-76. doi: 10.1017/S1355617717000637. Epub 2017 Aug 1. PMID: 28760172; PMCID: PMC5958545.

Schou TM, Joca S, Wegener G, Bay-Richter C. Psychiatric and neuropsychiatric sequelae of COVID-19 - A systematic review. Brain Behav Immun. 2021 Oct;97:328-348. doi: 10.1016/j.bbi.2021.07.018. Epub 2021 Jul 30. PMID: 34339806; PMCID: PMC8363196.

Singh CV, Jain S, Parveen S. The outcome of fluticasone nasal spray on anosmia and triamcinolone oral paste in dysgeusia in COVID-19 patients. Am J Otolaryngol. 2021 May-Jun;42(3):102892. doi: 10.1016/j.amjoto.2020.102892. Epub 2021 Jan 16. PMID: 33493729; PMCID: PMC7972940.

Thawani, Sujata, et al. “The Post-Acute Sequelae of Covid-19 (PASC) Experience in an Outpatient Neurology Setting (S18.005).” Neurology, Wolters Kluwer Health, Inc. on Behalf of the American Academy of Neurology, 3 May 2022,

Vogrig A, Gigli GL, Bnà C, Morassi M. Stroke in patients with COVID-19: Clinical and neuroimaging characteristics. Neurosci Lett. 2021 Jan 19;743:135564. doi: 10.1016/j.neulet.2020.135564. Epub 2020 Dec 19. PMID: 33352277; PMCID: PMC7749733.

Whitehurst LN, Cellini N, McDevitt EA, Duggan KA, Mednick SC. Autonomic activity during sleep predicts memory consolidation in humans. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7272-7. doi: 10.1073/pnas.1518202113. Epub 2016 Jun 13. PMID: 27298366; PMCID: PMC4932927.

Zhang S, Zhang J, Wang C, Chen X, Zhao X, Jing H, Liu H, Li Z, Wang L, Shi J. COVID‑19 and ischemic stroke: Mechanisms of hypercoagulability (Review). Int J Mol Med. 2021 Mar;47(3):21. doi: 10.3892/ijmm.2021.4854. Epub 2021 Jan 15. PMID: 33448315; PMCID: PMC7849983.

“Overview of Covid-19 Vaccines.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, approved%20 or,be%20given%20 in%20some%20 situations.

“People with Certain Medical Conditions.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention,

“Weekly Epidemiological Update on COVID-19 - 14 December 2022.” World Health Organization, World Health Organization,