Top

Published in:

Open Access 01-12-2021 | Guillain-Barré Syndrome | Research article

Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study

Authors: Man Amanat, Nima Rezaei, Mehrdad Roozbeh, Maziar Shojaei, Abbas Tafakhori, Anahita Zoghi, Ilad Alavi Darazam, Mona Salehi, Ehsan Karimialavijeh, Behnam Safarpour Lima, Amir Garakani, Alexander Vaccaro, Mahtab Ramezani

Published in: BMC Neurology | Issue 1/2021

Abstract

Backgrounds

The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death.

Methods

Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements.

Results

We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up.

Conclusion

Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5.CrossRefPubMedPubMedCentral

Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, Tan KS, Wang DY, Yan Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Mil Med Res. 2020;7(1):11. https://doi.org/10.1186/s40779-020-00240-0.CrossRefPubMedPubMedCentral

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–3. https://doi.org/10.1038/s41586-020-2012-7.CrossRefPubMedPubMedCentral

Zhang T, Wu Q, Zhang Z. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Curr Biol. 2020;30(7):1346–51. https://doi.org/10.1016/j.cub.2020.03.022.CrossRefPubMedPubMedCentral

Malaiyan J, Arumugam S, Mohan K, Gomathi RG. An update on the origin of SARS-CoV-2: despite closest identity, bat (RaTG13) and pangolin derived coronaviruses varied in the critical binding site and O-linked glycan residues. J Med Virol Published Online July 7. 2020;(1):499–505. https://doi.org/10.1002/jmv.26261.

Worldometers. COVID-19 coronavirus pandemic. Worldometers 2020.

Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y. 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. 2020;277(8):2251–61. https://doi.org/10.1007/s00405-020-05965-1.CrossRefPubMedPubMedCentral

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683–90. https://doi.org/10.1001/jamaneurol.2020.1127.CrossRefPubMed

Nepal G, Rehrig JH, Shrestha GS, Shing YK, Yadav JK, Ojha R, Pokhrel G, Tu ZL, Huang DY. Neurological manifestations of COVID-19: a systematic review. Crit Care. 2020;24(1):421. https://doi.org/10.1186/s13054-020-03121-z.CrossRefPubMedPubMedCentral

10.

Shahjouei S, Naderi S, Li J, Khan A, Chaudhary D, Farahmand G, Male S, Griessenauer C, Sabra M, Mondello S, Cernigliaro A, Khodadadi F, Dev A, Goyal N, Ranji-Burachaloo S, Olulana O, Avula V, Ebrahimzadeh SA, Alizada O, Hancı MM, Ghorbani A, Vaghefi far A, Ranta A, Punter M, Ramezani M, Ostadrahimi N, Tsivgoulis G, Fragkou PC, Nowrouzi-Sohrabi P, Karofylakis E, Tsiodras S, Neshin Aghayari Sheikh S, Saberi A, Niemelä M, Rezai Jahromi B, Mowla A, Mashayekhi M, Bavarsad Shahripour R, Sajedi SA, Ghorbani M, Kia A, Rahimian N, Abedi V, Zand R. Risk of stroke in hospitalized SARS-CoV-2 infected patients: a multinational study. EBioMedicine. 2020;59:102939. https://doi.org/10.1016/j.ebiom.2020.102939.CrossRefPubMedPubMedCentral

11.

Avci A, Yesiloglu O, Avci BS, Sumbul HE, BugraYapici S, Kuvvetli A, Pekoz BC, Cinar H, Satar S. Spontaneous subarachnoidal hemorrhage in patients with Covid-19: case report. J Neuro-Oncol. 2020;26(5):802–4. https://doi.org/10.1007/s13365-020-00888-3.CrossRef

12.

Swarz JA, Daily S, Niemi E, Hilbert SG, Ibrahim HA, Gaitanis JN. COVID-19 infection presenting as acute-onset focal status epilepticus. Pediatr Neurol. 2020;112:7. https://doi.org/10.1016/j.pediatrneurol.2020.07.012.CrossRefPubMedPubMedCentral

13.

McCuddy M, Kelkar P, Zhao Y, Wicklund D. Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 infection: A Case Series. medRxiv. https://doi.org/10.1101/2020.07.15.20126730.

14.

Tsai L, Hsieh S, Chang Y. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwanica. 2005;14(3):113–9.

15.

Arabi YM, Harthi A, Hussein J, Bouchama A, Johani S, Hajeer AH, Saeed BT, Wahbi A, Saedy A, AlDabbagh T, Okaili R. Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV). Infection. 2015;43(4):495–501. https://doi.org/10.1007/s15010-015-0720-y.CrossRefPubMedPubMedCentral

16.

Ellul M, Benjamin L, Singh B, Lant S, Michael B, Kneen R, Defres S, Sejvar J, Solomon T. Neurological Associations of COVID-19. 2020;19(9):767–783.

17.

World Health Organization. Clinical management of severe acute respiratory infection when Novel coronavirus (nCoV) infection is suspected: interim guidance. 2020. https://apps.who.int/iris/handle/10665/330893

18.

Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, Griffin MR. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45–67. https://doi.org/10.1164/rccm.201908-1581ST.CrossRefPubMedPubMedCentral

19.

Headache Classification Committee of the International Headache Society. The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38:1–211.

20.

Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20(7):864–70. https://doi.org/10.1161/01.STR.20.7.864.CrossRefPubMed

21.

Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH Score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32(4):891–897, DOI: https://doi.org/10.1161/01.STR.32.4.891.

22.

Umapathi T, Kor AC, Venketasubramanian N, Lim CT, Pang BC, Yeo TT, Lee CC, Lim PL, Ponnudurai K, Chuah KL, Tan PH. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol. 2004;251(10):1227–31. https://doi.org/10.1007/s00415-004-0519-8.CrossRefPubMedPubMedCentral

23.

Kwong KC, Mehta PR, Shukla G, Mehta AR. COVID-19, SARS and MERS: a neurological perspective. J Clin Neurosci. 2020;77:13–6. https://doi.org/10.1016/j.jocn.2020.04.124.CrossRef

24.

Khatoon F, Prasad K, Kumar V. Neurological manifestations of COVID-19: available evidences and a new paradigm. J Neuro-Oncol. 2020;26(5):619–30. https://doi.org/10.1007/s13365-020-00895-4.CrossRef

25.

Li G, He X, Zhang L, Ran Q, Wang J, Xiong A, Wu D, Chen F, Sun J, Chang C. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J Autoimmun. 2020;13:102463.CrossRef

26.

Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G. Is COVID-19 an endothelial disease? Clinical and basic evidence. Preprints. 2020. https://doi.org/10.20944/preprints202004.0204.v1.

27.

Aghagoli G, Marin BG, Katchur NJ, Chaves-Sell F, Asaad WF, Murphy SA. Neurological involvement in COVID-19 and potential mechanisms: a review. Neurocrit Care. 2020. https://doi.org/10.1007/s12028-020-01049-4.

28.

Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, Ueno M, Sakata H, Kondo K, Myose N, Nakao A. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020;94:55–8. https://doi.org/10.1016/j.ijid.2020.03.062.CrossRefPubMedPubMedCentral

29.

Virhammar J, Kumlien E, Fällmar D, Frithiof R, Jackmann S, Sköld MK, Kadir M, Frick J, Lindeberg J, Olivero-Reinius H, Ryttlefors M. Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid. Neurology. 2020;95(10):445–9. https://doi.org/10.1212/WNL.0000000000010250.CrossRefPubMedPubMedCentral

30.

Domingues RB, Mendes-Correa MC, de Moura Leite FB, Sabino EC, Salarini DZ, Claro I, Santos DW, de Jesus JG, Ferreira NE, Romano CM, Soares CA. First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease. J Neurol. 2020;267(11):3154–6. https://doi.org/10.1007/s00415-020-09996-w.CrossRefPubMedPubMedCentral

31.

Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020;92(7):699–702. https://doi.org/10.1002/jmv.25915.CrossRefPubMed

32.

Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, Braun F. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med. 2020;383(6):590–2. https://doi.org/10.1056/NEJMc2011400.CrossRefPubMed

33.

Pezzini A, Padovani A. Lifting the mask on neurological manifestations of COVID-19. Nat Rev Neurol. 2020;16(11):636–44. https://doi.org/10.1038/s41582-020-0398-3.CrossRefPubMedPubMedCentral

34.

Schaller T, Hirschbühl K, Burkhardt K, Braun G, Trepel M, Märkl B, Claus R. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518–20. https://doi.org/10.1001/jama.2020.8907.CrossRefPubMedPubMedCentral

35.

Solomon IH, Normandin E, Bhattacharyya S, Mukerji SS, Keller K, Ali AS, Adams G, Hornick JL, Padera RF Jr, Sabeti P. Neuropathological features of Covid-19. N Engl J Med. 2020;383(10):989–92. https://doi.org/10.1056/NEJMc2019373.CrossRefPubMed

36.

Pedersen SF, Ho YC. SARS-CoV-2: a storm is raging. J Clin Invest. 2020;130(5):2202–5. https://doi.org/10.1172/JCI137647.CrossRefPubMedPubMedCentral

37.

Aggarwal S, Garcia-Telles N, Aggarwal G, Lavie C, Lippi G, Henry BM. Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): early report from the United States. Diagnosis. 2020;7(2):91–6. https://doi.org/10.1515/dx-2020-0046.CrossRefPubMed

38.

Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis. 2020; Published online March 26, 2020.

39.

Moein ST, Hashemian SM, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL. Smell dysfunction: a biomarker for COVID-19. Int Forum Allergy Rhinol. 2020. Published online: April 17, 2020. https://doi.org/10.1002/alr.22587, Smell dysfunction: a biomarker for COVID‐19;8:950.

40.

Giorli A, Ferretti F, Biagini C, Salerni L, Bindi I, Dasgupta S, Pozza A, Gualtieri G, Gusinu R, Coluccia A, Mandalà M. A literature systematic review with meta-analysis of symptoms prevalence in Covid-19: the relevance of olfactory symptoms in infection not requiring hospitalization. Curr Treat Options Neurol. 2020;22(10):1–4.CrossRef

41.

Avcı H, Karabulut B, Farasoglu A, Boldaz E, Evman M. Relationship between anosmia and hospitalisation in patients with coronavirus disease 2019: an otolaryngological perspective. J Laryngol Otol. 2020;134(8):710–6. https://doi.org/10.1017/S0022215120001851.CrossRefPubMed

42.

Talavera B, García-Azorín D, Martínez-Pías E, Trigo J, Hernández-Pérez I, Valle-Peñacoba G, Simón-Campo P, de Lera M, Chavarría-Miranda A, López-Sanz C, Gutiérrez-Sánchez M. Anosmia is associated with lower in-hospital mortality in COVID-19. J Neurol Sci. 2020;419:117163. https://doi.org/10.1016/j.jns.2020.117163.CrossRefPubMedPubMedCentral

43.

Hopkins C, Surda P, Whitehead E, Kumar BN. Early recovery following new onset anosmia during the COVID-19 pandemic–an observational cohort study. J Otolaryngol Head Neck Surg. 2020;49:1–6.CrossRef

44.

Paolo G. Does COVID-19 cause permanent damage to olfactory and gustatory function? Med Hypotheses. 2020;143:110086. https://doi.org/10.1016/j.mehy.2020.110086.CrossRefPubMedPubMedCentral

45.

Hopkins C, Surda P, Vaira LA, Lechien JR, Safarian M, Saussez S, Kumar N. Six month follow-up of self-reported loss of smell during the COVID-19 pandemic. Rhinology. 2020. https://doi.org/10.4193/rhin20.544.

46.

Fu L, Wang B, Yuan T, Chen X, Ao Y, Fitzpatrick T, Li P, Zhou Y, Lin Y, Duan Q, Luo G. Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis. J Inf Secur. 2020;80(6):656–65. https://doi.org/10.1016/j.jinf.2020.03.041.CrossRef

47.

Trigo J, García-Azorín D, Planchuelo-Gómez Á, Martínez-Pías E, Talavera B, Hernández-Pérez I, Valle-Peñacoba G, Simón-Campo P, de Lera M, Chavarría-Miranda A, López-Sanz C. Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study. J Headache Pain. 2020;21(1):94. https://doi.org/10.1186/s10194-020-01165-8.CrossRefPubMedPubMedCentral

48.

Sampaio Rocha-Filho PA, Magalhães JE. Headache associated with COVID-19: frequency, characteristics and association with anosmia and ageusia. Cephalalgia. 2020;40(13):1443–51. https://doi.org/10.1177/0333102420966770.CrossRef

49.

Li Y, Wang M, Zhou Y, Chang J, Xian Y, Mao L, Hong C, Chen S, Wang Y, Wang H, Li M. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. SSRN Electron J. 2020;19. https://doi.org/10.2139/ssrn.3550025.

50.

Ramos-Araque ME, Siegler JE, Ribo M, Requena M, López C, de Lera M, Arenillas JF, Pérez IH, Gómez-Vicente B, Talavera B, Portela PC. Stroke etiologies in patients with COVID-19: the SVIN COVID-19 multinational registry. BMC Neurol. 2021;21(1):43. https://doi.org/10.1186/s12883-021-02075-1.CrossRefPubMedPubMedCentral

51.

Zoghi A, Ramezani M, Roozbeh M, Darazam IA, Sahraian MA. A case of possible atypical demyelinating event of the central nervous system following COVID-19. Multiple Sclerosis Related Disord. 2020;44:102324. https://doi.org/10.1016/j.msard.2020.102324.CrossRef

52.

Lampert PW, Sims JK, Kniazeff AJ. Mechanism of demyelination in JHM virus encephalomyelitis. Acta Neuropathol. 1973;24(1):76–85. https://doi.org/10.1007/BF00691421.CrossRefPubMedPubMedCentral

53.

Hosking MP, Lane TE. The pathogenesis of murine coronavirus infection of the central nervous system. Crit Rev Immunol. 2010;30(2):119–30. https://doi.org/10.1615/CritRevImmunol.v30.i2.20.CrossRefPubMedPubMedCentral

54.

Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011;36(2):123–33. https://doi.org/10.1159/000324710.CrossRefPubMed

55.

Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, Franciotta D, Baldanti F, Daturi R, Postorino P, Cavallini A. Guillain–Barré syndrome associated with SARS-CoV-2. N Engl J Med. 2020;382(26):2574–6. https://doi.org/10.1056/NEJMc2009191.CrossRefPubMed

56.

Sriwastava S, Kataria S, Tandon M, Patel J, Patel R, Jowkar A, Daimee M, Bernitsas E, Jaiswal P, Lisak RP. Guillain Barré syndrome and its variants as a manifestation of COVID-19: a systemic review of case report and case series. J Neurol Sci. 2021;420:117263. https://doi.org/10.1016/j.jns.2020.117263.CrossRefPubMed

57.

Abu-Rumeileh S, Abdelhak A, Foschi M, Tumani H, Otto M. Guillain–Barré syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases. J Neurol. Published online 25 August. 2020. https://doi.org/10.1007/s00415-020-10124-x.

Title: Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study
Authors: Man Amanat
Nima Rezaei
Mehrdad Roozbeh
Maziar Shojaei
Abbas Tafakhori
Anahita Zoghi
Ilad Alavi Darazam
Mona Salehi
Ehsan Karimialavijeh
Behnam Safarpour Lima
Amir Garakani
Alexander Vaccaro
Mahtab Ramezani
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Guillain-Barré Syndrome
Stroke
Myalgie
Myalgia
SARS-CoV-2
COVID-19
Headache
Anosmia
Published in: BMC Neurology / Issue 1/2021
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-021-02152-5

2024 ASCO Annual Meeting

Springer Medicine

Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study

Abstract

Backgrounds

Methods

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Backgrounds

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Translation and validation of the Persian version of Godin Leisure-Time Exercise Questionnaire in patients with multiple sclerosis

Prognostic value of the neutrophil-to-lymphocyte ratio in acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis

Association between estimated glomerular filtration rate and clinical outcomes in ischemic stroke patients with high-grade carotid artery stenosis

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy

Mild cognitive impairment in novel SPG11 mutation-related sporadic hereditary spastic paraplegia with thin corpus callosum: case series

The long‐term outcome of neuropsychological function is favorable in patients with non‐malignancy related anti-GABABR encephalitis: a case series