Neurological Consequences of COVID-19


The knowledge and understanding of COVID-19 and its consequences is progressing, giving better insight into the heterogeneous nature of its acute and long-term effects. The available evidence on the pulmonary, cardiovascular, neurological, hematological, multisystem inflammatory, endocrine, renal, gastrointestinal, and integumentary sequelae show that COVID-19 continues after acute infection. [1]

Neurological complications of COVID-19 can range from headache, chronic pain, loss of smell, mental confusion‎, and dizziness‎ to more life-threatening consequences such as stroke, encephalitis, coma, and Guillain-Barre ‎syndrome. [2-3]

One study showed that around one-third of COVID-19 patients may experience persistent neurologic symptoms‎.[4] Moreover, chronic pain has become one of the hallmarks of long-term COVID impacting not only the chronic pain populations but also causing new-onset chronic pain in many others.[5]

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Many factors contribute to a higher risk of these complications. Those with more severe COVID-19 infection or higher respiratory involvement were more likely to have neurological complications.[6-7] Patients with preexisting neurological conditions had an elevated risk of aggravating their conditions.[8] Furthermore, vitamin D deficiency was associated with the development of severe forms of COVID-19 including neurological sequelae.[9] On the other hand, vaccination was shown as a protective factor. Neurological complications were up to ‎617-fold ‎less frequent after vaccination.[10]

The mechanism of these clinical manifestations could be attributed to direct SARS-CoV-2 invasion into the ‎central nervous system. The virus enters the body via the ACE-2 receptors in the central nervous system, which causes the body to balance an immune response against potential damage to nonrenewable cells. Another mechanism is the indirect effects of systemic infection.[11]

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  1. Joshee S, Vatti N, Chang C. Long-Term Effects of COVID-19. Mayo Clin Proc. 2022 Mar;97(3):579-599. doi: 10.1016/j.mayocp.2021.12.017. Epub 2022 Jan 12. PMID: 35246288; PMCID: PMC8752286.

  2.  Veleri S. Neurotropism of SARS-CoV-2 and neurological diseases of the central nervous system in COVID-19 patients. Exp Brain Res. 2022 Jan;240(1):9-25. doi: 10.1007/s00221-021-06244-z. Epub 2021 Oct 25. PMID: 34694467; PMCID: PMC8543422.

  3.  Dangayach NS, Newcombe V, Sonnenville R. Acute Neurologic Complications of COVID-19 and Postacute Sequelae of COVID-19. Crit Care Clin. 2022 Jul;38(3):553-570. doi: 10.1016/j.ccc.2022.03.002. Epub 2022 Mar 23. PMID: 35667743; PMCID: PMC8940578.

  4.  Graham EL, Koralnik IJ, Liotta EM. Therapeutic Approaches to the Neurologic Manifestations of COVID-19. Neurotherapeutics. 2022 Jul 21:1–32. doi: 10.1007/s13311-022-01267-y. Epub ahead of print. PMID: 35861926; PMCID: PMC9302225.

  5.  Shanthanna H, Nelson AM, Kissoon N, Narouze S. The COVID-19 pandemic and its consequences for chronic pain: a narrative review. Anaesthesia. 2022 Sep;77(9):1039-1050. doi: 10.1111/anae.15801. Epub 2022 Jul 18. PMID: 35848380; PMCID: PMC9350079.

  6.  Li D, Wang Q, Jia C, Lv Z, Yang J. An Overview of Neurological and Psychiatric Complications During Post-COVID Period: A Narrative Review. J Inflamm Res. 2022 Jul 26;15:4199-4215. doi: 10.2147/JIR.S375494. PMID: 35923904; PMCID: PMC9342586.

  7.  Ahmed A Ibrahim E, Isam Farah Hassan R, Abbasher Hussien Mohamed Ahmed K, Taha Salah E, Eltahier Abdalla Omer M, S Haroun M. Neurological manifestations of COVID-19: A potential gate to the determinants of a poor prognosis. Brain Behav. 2022 Jun;12(6):e2587. doi: 10.1002/brb3.2587. Epub 2022 Apr 25. PMID: 35470588; PMCID: PMC9110897.

  8.  Pergolizzi JV Jr, Raffa RB, Varrassi G, Magnusson P, LeQuang JA, Paladini A, Taylor R, Wollmuth C, Breve F, Chopra M, Nalamasu R, Christo PJ; NEMA Research Group. Potential neurological manifestations of COVID-19: a narrative review. Postgrad Med. 2022 May;134(4):395-405. doi: 10.1080/00325481.2020.1837503. Epub 2021 Jan 11. PMID: 33089707; PMCID: PMC7799377.

  9.  Menéndez SG, Martín Giménez VM, Holick MF, Barrantes FJ, Manucha W. COVID-19 and neurological sequelae: Vitamin D as a possible neuroprotective and/or neuroreparative agent. Life Sci. 2022 May 15;297:120464. doi: 10.1016/j.lfs.2022.120464. Epub 2022 Mar 7. PMID: 35271880; PMCID: PMC8898786.

  10.  Frontera JA, Tamborska AA, Doheim MF, Garcia-Azorin D, Gezegen H, Guekht A, Yusof Khan AHK, Santacatterina M, Sejvar J, Thakur KT, Westenberg E, Winkler AS, Beghi E; contributors from the Global COVID-19 Neuro Research Coalition. Neurological Events Reported after COVID-19 Vaccines: An Analysis of VAERS. Ann Neurol. 2022 Mar 2;91(6):756–71. doi: 10.1002/ana.26339. Epub ahead of print. PMID: 35233819; PMCID: PMC9082459.

  11.  Sarubbo F, El Haji K, Vidal-Balle A, Bargay Lleonart J. Neurological consequences of COVID-19 and brain related pathogenic mechanisms: A new challenge for neuroscience. Brain Behav Immun Health. 2022 Feb;19:100399. doi: 10.1016/j.bbih.2021.100399. Epub 2021 Nov 30. PMID: 34870247; PMCID: PMC8629776.
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