AccScience Publishing / AN / Volume 1 / Issue 2 / DOI: 10.36922/an.v1i2.83
Cite this article
83
Download
2058
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
REVIEW

Neurological complications of coronavirus disease 2019 and the underlying mechanisms

Zhiyuan Yang1 Chenglu Mao1 Qiaochu Guan2 Weiping Lv3 Yanan Huang3 Huahong Zhu4 Yun Xu1,5,6,7*
Show Less
1 Department of Neurology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
2 Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
3 Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China
4 Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
5 The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing, China
6 Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China
7 Jiangsu Province Stroke Center for Diagnosis and Therapy, China Nanjing Neurology Clinic Medical Center, Nanjing, China
Advanced Neurology 2022, 1(2), 83 https://doi.org/10.36922/an.v1i2.83
Submitted: 5 May 2022 | Accepted: 7 July 2022 | Published: 18 August 2022
© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

The recent global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory symptoms are the primary manifestation of the majority of COVID-19 patients, an increasing number of neurological symptoms and manifestations of COVID-19 have been observed. In this review, we detail the neurological complications of COVID-19, such as gustatory and olfactory dysfunctions, stroke, memory decline, muscle injury, and seizures. Furthermore, we introduce neural invasion mechanism underlying SARS-CoV-2 infection and, further, explain the occurrence of these complications. This review offers insights into the neurological signs and symptoms of COVID-19, which may help improve the prognosis of the infected patients.

Keywords
COVID-19
Neurological complications
Clinic characteristics
Neural invasion
Funding
National Natural Science Foundation of China
Key Research and Development Program of Jiangsu Province of China
Conflict of interest
The authors have no competing interest to declare.
References
[1]

Feng W, Zong W, Wang F, et al., 2020, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A review. Mol Cancer, 19(1): 100. https://doi.org/10.1186/s12943-020-01218-1

[2]

Bhatraju PK, Ghassemieh BJ, Nichols M, et al., 2020, Covid- 19 in critically ill patients in the Seattle Region case series. N Engl J Med, 382(21): 2012–2022. https://doi.org/10.1056/NEJMoa2004500

[3]

Spinato G, Fabbris C, Polesel J, et al., 2020, Alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection. JAMA, 323(20): 2089–2090. https://doi.org/10.1001/jama.2020.6771

[4]

Boscolo-Rizzo P, Borsetto D, Fabbris C, et al., 2020, Evolution of altered sense of smell or taste in patients with mildly symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg, 146(8): 729–732. https://doi.org/10.1001/jamaoto.2020.1379

[5]

Jalessi M, Barati M, Rohani M, et al., 2020, Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19. Neurol Sci, 41(9): 2331–2338. https://doi.org/10.1007/s10072-020-04590-4

[6]

Boscolo-Rizzo P, Menegaldo A, Fabbris C, et al., 2021, Six-month psychophysical evaluation of olfactory dysfunction in patients with COVID-19. Chem Senses, 46: bjab006. https://doi.org/10.1093/chemse/bjab006

[7]

Printza A, Katotomichelakis M, Valsamidis K, et al., 2021, Smell and taste loss recovery time in COVID-19 patients and disease severity. J Clin Med, 10(5): 966. https://doi.org/10.3390/jcm10050966 

[8]

Rojas-Lechuga MJ, Izquierdo-Dominguez A, Chiesa- Estomba C, et al., 2021, Chemosensory dysfunction in COVID-19 out-patients. Eur Arch Otorhinolaryngol, 278(3): 695–702. https://doi.org/10.1007/s00405-020-06266-3

[9]

Hajikhani B, Calcagno T, Nasiri MJ, et al., 2020, Olfactory and gustatory dysfunction in COVID-19 patients: A meta-analysis study. Physiol Rep, 8(18): e14578. https://doi.org/10.14814/phy2.14578

[10]

Ibekwe TS, Fasunla AJ, Orimadegun AE. 2020, Systematic review and meta-analysis of smell and taste disorders in COVID-19. OTO Open, 4(3): 2473974X20957975. https://doi.org/10.1177/2473974X20957975

[11]

Giacomelli A, Pezzati L, Conti F, et al., 20250, Self-reported olfactory and taste disorders in SARS-CoV-2 patients: A cross-sectional study. Clin Infect Dis, 71(15): 889–890. https://doi.org/10.1093/cid/ciaa330

[12]

Biadsee A, Dagan O, Ormianer Z, et al., 2021, Eight-month follow-up of olfactory and gustatory dysfunctions in recovered COVID-19 patients. Am J Otolaryngol, 42(4): 103065. https://doi.org/10.1016/j.amjoto.2021.103065

[13]

Romero-Sanchez CM, Diaz-Maroto I, Fernandez-Diaz E, et al., 2020, Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry. Neurology, 95(8): e1060–e1070. https://doi.org/10.1212/WNL.0000000000009937

[14]

Meng X, Deng Y, Dai Z, et al., 2020, COVID-19 and anosmia: A review based on up-to-date knowledge. Am J Otolaryngol, 41(5): 102581. https://doi.org/10.1016/j.amjoto.2020.102581

[15]

Kumar L, Kahlon N, Jain A, et al., 2021, Loss of smell and taste in COVID-19 infection in adolescents. Int J Pediatr Otorhinolaryngol, 142: 110626. https://doi.org/10.1016/j.ijporl.2021.110626

[16]

Lechien J, Chiesa-Estomba C, De Siati D, et al., 2020, Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study. Eur Arch Otorhinolaryngol, 277(8): 2251–2261. https://doi.org/10.1007/s00405-020-05965-1

[17]

Chen R, Wang K, Yu J, et al., 2021, The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in the human and mouse brains. Front Neurol, 11: 573095.

[18]

Brann DH, Tsukahara T, Weinreb C, et al., 2020, Non-neuronal expression of SARS-CoV-2 entry genes in the olfaory system suggests mechanisms underlying COVID- 19-associated anosmia. Sci Adv, 6(31): eabc5801. https://doi.org/10.1126/sciadv.abc5801

[19]

Lechien JR, Chiesa-Estomba CM, De Siati DR, et al., 2020, Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study. Eur Arch Otorhinolaryngol, 277(8): 2251–2261. https://doi.org/10.1007/s00405-020-05965-1

[20]

Whitcroft KL, Hummel T. 2020, Olfactory dysfunction in COVID-19 diagnosis and management. JAMA, 3(24): 2512– 2514. https://doi.org/10.1001/jama.2020.8391

[21]

Pun BT, Badenes R, Heras G, et al., 2021, Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): A multicentre cohort study. Lancet Respir Med, 9(3): 239–250. https://doi.org/10.1016/S2213-2600(20)30552-X 

[22]

Girard TD, Jackson JC, Pandharipande PP, et al., 2010, Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med, 38(7): 1513–1520. https://doi.org/10.1097/CCM.0b013e3181e47be1

[23]

Liu YH, Chen Y, Wang QH, et al., 2022, One-year trajectory of cognitive changes in older survivors of COVID-19 in Wuhan, China: A longitudinal cohort study. JAMA Neurol, 79(5): 509–517. https://doi.org/10.1001/jamaneurol.2022.0461

[24]

Blomberg B, Mohn KG, Brokstad KA, et al., 2021, Long COVID in a prospective cohort of home-isolated patients. Nat Med, 27(9): 1607–1613. https://doi.org/10.1038/s41591-021-01433-3

[25]

Yerlikaya D, Emek-Savaş DD, Kurşun BB, et al., 2018, Electrophysiological and neuropsychological outcomes of severe obstructive sleep apnea: Effects of hypoxemia on cognitive performance. Cogn Neurodyn, 12(5): 471–480. https://doi.org/10.1007/s11571-018-9487-z

[26]

Safavynia SA, Arora S, Pryor KO, et al., 2018, An update on postoperative delirium: Clinical features, neuropathogenesis, and perioperative management. Curr Anesthesiol Rep, 8(3): 252–262.

[27]

Safavynia SA, Goldstein PA. 2019, The role of neuroinflammation in postoperative cognitive dysfunction: Moving from hypothesis to treatment. Front Psychiatry, 9: 752. https://doi.org/10.3389/fpsyt.2018.00752

[28]

Cecchetti G, Agosta F, Canu E, et al., 2022, Cognitive, EEG, and MRI features of COVID-19 survivors: A 10-month study. J Neurol, 269(7): 3400–3412. https://doi.org/10.1007/s00415-022-11047-5

[29]

Hosp JA, Dressing A, Blazhenets G, et al., 2021, Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain, 144(4): 1263–1276. https://doi.org/10.1093/brain/awab009

[30]

Liu K, Pan M, Xiao Z, et al., 2020, Neurological manifestations of the coronavirus (SARS-CoV-2) pandemic 2019-2020. J Neurol Neurosurg Psychiatry, 91(6): 669–670. https://doi.org/10.1136/jnnp-2020-323177

[31]

Ali L, Mohammed I, Janjua I, et al., 2021, Acute myocardial injury and rhabdomyolysis in COVID-19 patients: Incidence and mortality. Cureus, 13(10): e18899. https://doi.org/10.7759/cureus.18899

[32]

Nasiri MJ, Haddadi S, Tahvildari A, et al., 2020, COVID-19 clinical characteristics, and sex-specific risk of mortality: Systematic review and meta-analysis. Front Med (Lausanne), 7: 459. https://doi.org/10.3389/fmed.2020.00459

[33]

Zhu J, Ji P, Pang J, et al., 2020, Clinical characteristics of 3062 COVID-19 patients: A meta-analysis. J Med Virol, 92(10): 1902–1914. https://doi.org/10.1002/jmv.25884

[34]

Huang C, Huang L, Wang Y, et al., 2021, 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet, 397(10270): 220–232. https://doi.org/10.1016/s0140-6736(20)32656-8

[35]

van den Borst B, Peters JB, Brink M, et al., 2019, Comprehensive health assessment 3 months after recovery from acute coronavirus disease 2019 (COVID-19). Clin Infect Dis, 73(5): e1089–e1098. https://doi.org/10.1093/cid/ciaa1750

[36]

Ali AM, Kunugi H. 2021, Approaches to nutritional screening in patients with coronavirus disease 2019 (COVID-19). Int J Environ Res Public Health, 18(5): 2772. https://doi.org/10.3390/ijerph18052772

[37]

Welch C, Greig C, Masud T, et al., 2020, COVID-19 and acute sarcopenia. Aging Dis, 11(6): 1345–1351. https://doi. org/10.14336/AD.2020.1014

[38]

Morley JE, Kalantar-Zadeh K, Anker SD. 2020, COVID: A major cause of cachexia and sarcopenia? J Cachexia Sarcopenia Muscle, 11(4): 863–865. https://doi.org/10.1002/jcsm.12589

[39]

Finsterer J, Scorza F. 2021, SARS-CoV-2 associated rhabdomyolysis in 32 patients. Turk J Med Sci, 51(3): 1598–1601. https://doi.org/10.3906/sag-2012-327

[40]

Lorenzo RD, Conte C, Lanzani C, et al., 2020, Residual clinical damage after COVID-19: A retrospective and prospective observational cohort study. PLoS One, 15(10): e0239570.

[41]

Geng Y, Ma Q, Du YS, et al., 2021, Rhabdomyolysis is associated with in-hospital mortality in patients with COVID-19. Shock, 56(3): 360–367. https://doi.org/10.1097/SHK.0000000000001725

[42]

Zhang Q, Schultz J, Aldridge G, Simmering J, et al., 2020, Coronavirus disease 2019 case fatality and Parkinson’s disease. Mov Disord, 35(11): 1914–1915. https://doi.org/10.1002/mds.28325

[43]

Yaghi S, Ishida K, Torres J, et al., 2020, SARS2-CoV-2 and stroke in a New York healthcare system. Stroke, 51(5): 2002–2011. https://doi.org/10.1161/strokeaha.120.030335

[44]

Romero-Sánchez C, Díaz-Maroto I, Fernández-Díaz E, et al., 2020, Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry. Neurology, 95(8): e1060–e1070. https://doi.org/10.1212/WNL.0000000000009937

[45]

Fridman S, Bres Bullrich M, Jimenez-Ruiz A, et al., 2020, Stroke risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases. Neurology, 95(24): e3373– e3385. https://doi.org/10.1212/WNL.0000000000010851

[46]

Merkler AE, Parikh NS, Mir S, et al., 2020, Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol, 77(11): 1–7. https://doi.org/10.1001/jamaneurol.2020.2730

[47]

Dhamoon MS, Thaler A, Gururangan K, et al., 2021, Acute cerebrovascular events with COVID-19 infection. Stroke, 52(1):48–56. https://doi.org/10.1161/STROKEAHA.120.031668

[48]

Harzallah I, Debliquis A, Drénou B. 2020, Lupus anticoagulant is frequent in patients with Covid‐19. J Thromb Haemost, 18(8): 2064–2065. https://doi.org/10.1111/jth.14867

[49]

Zhang Y, Xiao M, Zhang S, et al., 2020, Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med, 382(17): e38. https://doi.org/10.1056/NEJMc2007575

[50]

Zhou F, Yu T, Du R, et al., 2020, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet, 395(10229): 1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3

[51]

Lu L, Xiong W, Liu D, et al., 2020, New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study. Epilepsia, 61(6): e49–e53. https://doi.org/10.1111/epi.16524

[52]

Lodigiani C, Iapichino G, Carenzo L, et al., 2020, Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res, 191: 9–14. https://doi.org/10.1016/j.thromres.2020.04.024

[53]

Cui S, Chen S, Li X, et al., 2020, Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost, 18(6): 1421–1424. https://doi.org/10.1111/jth.14830

[54]

Janes F, Gigli GL, Kuris F, et al., 2022, Failure of therapeutic anticoagulation in COVID-19 patients with acute ischemic stroke. A retrospective multicenter study. Front Neurol, 13: 834469. https://doi.org/10.3389/fneur.2022.834469

[55]

Shakibajahromi B, Borhani-Haghighi A, Haseli S, et al., 2020, Cerebral venous sinus thrombosis might be under-diagnosed in the COVID-19 era. eNeurologicalSci, 20: 100256. https://doi.org/10.1016/j.ensci.2020.100256

[56]

Abdalkader M, Shaikh SP, Siegler JE, et al., 2021, Cerebral venous sinus thrombosis in COVID-19 patients: A multicenter study and review of literature sciencedirect. J Stroke Cerebrovasc Dis, 30(6): 105733. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105733

[57]

Kow CS, Zaihan AF, Hasan SS. 2020, Anticoagulant approach in COVID-19 patients with cerebral venous thrombosis. J Stroke Cerebrovasc Dis, 29(12): 105222. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105222

[58]

Schulz JB, Berlit P, Diener HC, et al., 2021, COVID-19 vaccine-associated cerebral venous thrombosis in Germany. Ann Neurol, 90(4): 627–639. https://doi.org/10.1002/ana.26172

[59]

Lyons S, O’Kelly B, Woods S, et al., Seizure with CSF lymphocytosis as a presenting feature of COVID-19 in an otherwise healthy young man. Seizure, 80: 113–114. https://doi.org/10.1016/j.seizure.2020.06.010

[60]

Abdulsalam MA, Abdulsalam AJ, Shehab D. Generalized status epilepticus as a possible manifestation of COVID-19. Acta Neurol Scand, 142(4): 297–298. https://doi.org/10.1111/ane.13321

[61]

Asadi-Pooya AA. 2020, Seizures associated with coronavirus infections. Seizure, 79: 49–52. https://doi.org/10.1016/j.seizure.2020.05.005

[62]

Hepburn M, Mullaguri N, George P, et al., 2021, Acute symptomatic seizures in critically ill patients with cOVID-19: Is there an association? Neurocrit Care, 34(1): 139–143. https://doi.org/10.1007/s12028-020-01006-1

[63]

Ashraf M, Sajed S. 2020, Seizures related to coronavirus disease (COVID-19): Case series and literature review. Cureus, 12(7): e9378. https://doi.org/10.7759/cureus.9378

[64]

Bhatta S, Sayed A, Ranabhat B, et al., 2020, New-onset seizure as the only presentation in a child with COVID-19. Cureus, 12(6): e8820. https://doi.org/10.7759/cureus.8820

[65]

Moriguchi T, Harii N, Goto N, et al., 2020, A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis, 94:55–58. https://doi.org/10.1016/j.ijid.2020.03.062

[66]

Mardani M, Nadji SA, Sarhangipor KA, et al., 2020, COVID-19 infection recurrence presenting with meningoencephalitis. New Microbes New Infect, 37: 100372. https://doi.org/10.1016/j.nmni.2020.100732

[67]

Bernard-Valnet R, Pizzarotti B, Anichini A, et al., 2020, Two patients with acute meningo-encephalitis concomitant to SARS-CoV-2 infection. Eur J Neurol, 27(9): e43–e44. https://doi.org/10.1111/ene.14298

[68]

Kaya Y, Kara S, Akinci C, et al., 2020, Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: Case report. J Neurol Sci, 413: 116858. https://doi.org/10.1016/j.jns.2020.116858

[69]

Papri N, Hayat S, Mohammed A, et al., 2021, Guillain-Barré syndrome associated with SARS-CoV-2 infection: A case report with long term follow up. J Neuroimmunol, 356(8): 577590. https://doi.org/10.1016/j.jneuroim.2021.577590

[70]

Tiet MY, Alshaikh N, 2020, Guillain-Barré syndrome associated with COVID-19 infection: A case from the UK. BMJ Case Rep, 13(7): e236536. https://doi.org/10.1136/bcr-2020-236536

[71]

Lascano AM, Epiney JB, Coen M, et al., 2020, SARS-CoV-2 and Guillain-Barre syndrome: AIDP variant with a favourable outcome. Eur J Neurol, 27(9): 1751-1753. https://doi.org/10.1111/ene.14368

[72]

Carod-Artal FJ, 2020, Neurological complications of coronavirus and COVID-19. Rev Neurol, 70(9): 311–322. https://doi.org/10.33588/rn.7009.2020179

[73]

Desforges M, Coupanec AL, Brison E, et al., 2014, Neuroinvasive and neurotropic human respiratory coronaviruses: Potential neurovirulent agents in humans. Adv Exp Med Biol, 807: 75–96.

[74]

Zhou Z, Kang H, Li S, et al., 2020, Understanding the neurotropic characteristics of SARS-CoV-2: From neurological manifestations of COVID-19 to potential neurotropic mechanisms. J Neurol, 267(10223): 2179–2184. https://doi.org/10.1007/s00415-020-09929-7

[75]

Desforges M, Coupanec AL, Dubeau P, et al., 2019, Human coronaviruses and other respiratory viruses: Underestimated opportunistic pathogens of the central nervous system? Viruses, 12(1): 14. https://doi.org/10.3390/v12010014

[76]

Prather KA, Wang CC, Schooley RT. 2020, Reducing transmission of SARS-CoV-2. Science, 368(6498): 1422–1424. https://doi.org/10.1126/science.abc6197

[77]

Mehta P, McAuley DF, Brown M, et al., 2020, COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet, 395(10229): 1033–1034. https://doi.org/10.1016/S0140-6736(20)30628-0

[78]

Adhikary A, Halder K, Ghosh D, et al., 2020, A review of anti-inflammatory drugs use in the treatment of people infected by coronavirus disease 2019 (COVID-19). Acta Sci Microbiol, 3: 28-34. https://doi.org/10.31080/ASMI.2020.03.0712

[79]

Durrant DM, Ghosh S, Klein RS, 2016, The olfactory bulb: An immunosensory effector organ during neurotropic viral infections. Acs Chem Neurosci, 7(4): 464–469. https://doi.org/10.1021/acschemneuro.6b00043

[80]

Netland J, Meyerholz DK, Moore S, et al., 2008, Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol, 82(15): 7264–7275. https://doi.org/10.1128/JVI.00737-08

[81]

Amirian ES. 2020, Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health. Int J Infect Dis, 95: 363–370. https://doi.org/10.1016/j.ijid.2020.04.057

[82]

Ahmed MU, Hanif M, Ali MJ, et al., 2020, Neurological manifestations of COVID-19 (SARS-CoV-2): A review. Front Neurol, 11: 518. https://doi.org/10.3389/fneur.2020.00518

[83]

Ludvigsson JF, 2022, Convulsions in children with COVID-19 during the Omicron wave. Acta Paediatr, 111(5): 1023–1026. https://doi.org/10.1111/apa.16276

[84]

Thongsing A, Eizadkhah D, Fields C, et al., 2022, Provoked seizures and status epilepticus in a pediatric population with COVID-19 disease. Epilepsia 10: 1111. https://doi.org/10.1111/epi.17293

[85]

Pinzon RT, Wijaya VO, Buana RB, et al., 2020, Neurologic characteristics in coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Front Neurol, 11: 565. https://doi.org/10.3389/fneur.2020.00565

[86]

Collantes M, Espiritu AI, Sy MC, et al., 2021, Neurological manifestations in COVID-19 infection: A systematic review and meta-analysis. Can J Neurol Sci, 48(1): 66–76. https://doi.org/10.1017/cjn.2020.146

Share
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing