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Licensed Unlicensed Requires Authentication Published by De Gruyter September 12, 2022

Covid-19 vaccines and neurological complications: a systematic review

  • Fakhri Allahyari ORCID logo , Hamideh Molaee EMAIL logo and Javad Hosseini Nejad ORCID logo

Abstract

The COVID-19 mainly causes respiratory disorders with high infection and severe morbidity and mortality. Neurologists have concerns about potential neurological side effects, profits, and timing of COVID-19 vaccines. This study aimed to review systematically research for the COVID-19 vaccine and neurological complications. Data was searched in Scopus, ISI web of knowledge, Medline, PubMed, Wiley, Embase, International Clinical Trials Registry Platform and Clinical Trials, Cochrane Library, and Google Scholar. Two reviewer authors individually searched and assessed the titles and abstracts of all articles. The third reviewer resolved disagreement between them. Data were documented regarding study location, study design, type of complications, number of patients, various types of COVID-19 vaccine, and type of neurological complications. Six studies in COVID-19 vaccine and neurological complications include two studies about neurological manifestations after the mRNA vaccines, four records about side effects of vector-based vaccine were included in the study. The main neurological complication associated mRNA vaccines were body aches, paresthesia, and difficulty walking, erythema migrans lesion, fatigue, myalgia, and pain in the left lateral deltoid region. The major neurological complication related to vector-based vaccines were urinary retention difficulty, feeding and ambulating, arm soreness, mild fatigue, chills, left-sided facial droop, headaches, a generalized epileptic seizure, hemianopia, and mild aphasia, acute somnolence and right-hand hemiparesis, acute transverse myelitis, deep vein thrombosis in her left leg, a vigilance disorder and a twitching, a severe immobilizing opsoclonus myoclonus syndrome, and encephalitis. A large spectrum of severe neurological unfavorable has been reported. These complications could occur as a result of molecular stimulation and later neuronal damage. Generally, the advantages of COVID‐19 vaccination are dominant on the risks of a neurological complication at both individual and population levels. Future investigations will be required to find any relationship between neurological complications and COVID‐19 vaccines principally as new strains of the virus and new vaccines are technologically advanced against them.


Corresponding author: Hamideh Molaee, Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Lu, H, Stratton, CW, Tang, YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle. J Med Virol 2020;92:401–2. https://doi.org/10.1002/jmv.25678.Search in Google Scholar PubMed PubMed Central

2. Espinosa, PS, Rizvi, Z, Sharma, P, Hindi, F, Filatov, A. Neurological complications of coronavirus disease (COVID- 19): encephalopathy, MRI brain and cerebrospinal fluid findings: case 2. Cureus 2020;12:e7930. https://doi.org/10.7759/cureus.7930.Search in Google Scholar PubMed PubMed Central

3. Mintoff, D, Pisani, D, Betts, A, Scerri, L. SARS-CoV-2 mRNA vaccineassociated fixed drug eruption. J Eur Acad Dermatol Venereol 2021;35:e560. https://doi.org/10.1111/jdv.17390.Search in Google Scholar PubMed

4. Sinha, A, Kumar, R, Raj Singh, A. Implication of mass COVID-19 vaccination on dermatology practice in 2021. Dermatol Ther 2021;34:e14765. https://doi.org/10.1111/dth.14765.Search in Google Scholar PubMed PubMed Central

5. Allen, A, Szabo, L, Kaiser Health News. NIH “very concerned” about serious side effect in coronavirus vaccine trial [Internet]. Scientific American; 2020. Available from: https://www.scientificamerican.com/article/nih-very-concerned-about-serious-side-effect-in-coronavirus-vaccine-trial/ [Accessed 27 Feb 2021].Search in Google Scholar

6. Voysey, M, Clemens, SAC, Madhi, SA, Weckx, LY, Folegatti, PM, Aley, PK, et al.. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99–111.10.1016/S0140-6736(20)32661-1Search in Google Scholar PubMed PubMed Central

7. Ledford, H. US authorization of first COVID vaccine marks new phase in safety monitoring. Nature 2020;588:377–8. https://doi.org/10.1038/d41586-020-03542-4.Search in Google Scholar PubMed

8. CDC. COVID-19 vaccination considerations for persons with underlying medica [Internet]. Centers for Disease Control and Prevention; 2021. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/underlying-conditions.html [Accessed 11 Mar 2021].Search in Google Scholar

9. Keddie, S, Pakpoor, J, Mousele, C, Pipis, M, Machado, PM, Foster, M, et al.. Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome. Brain 2021;144:682–93.10.1093/brain/awaa433Search in Google Scholar PubMed PubMed Central

10. Gee, J. First month of COVID-19 vaccine safety monitoring United States December 14 2020 – January 13 2021 [Internet]. MMWR Morb Mortal Wkly Rep 2021;70:283–8.10.15585/mmwr.mm7008e3Search in Google Scholar PubMed PubMed Central

11. IDSA COVID-19 Real Time Learning Network Editorial Staff. COVID-19 real-time learning network: vaccines FAQ. [Internet]; 2021. Available from: https://www.idsociety.org/covid-19-real-time-learning-network/vaccines/vaccines-information-faq/ [Accessed 27 February 2021].Search in Google Scholar

12. Ciotti, JR, Valtcheva, MV, Cross, AH. Effects of MS disease-modifying therapies on responses to vaccinations: a review. Mult Scler Relat Disord 2020;45:102439.. https://doi.org/10.1016/j.msard.2020.102439.Search in Google Scholar PubMed PubMed Central

13. Achiron, A, Mandel, M, Dreyer-Alster, S, Harari, G, Magalashvili, D, Sonis, P, et al.. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Ther Adv Neurol Disord 2021;14:17562864211012835.10.1177/17562864211012835Search in Google Scholar PubMed PubMed Central

14. World Health Organization. Draft landscape and tracker of COVID-19 candidate vaccines. 2020. https://www.who. int/publications/m/item/draft-landscape-of-COVID-19-candidate-vaccines.Search in Google Scholar

15. Ramasamy, M, Minassian, AM. Safety and immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccine administered in a prime- boost regimen in older adults (COV002): a phase 2/3 single blind, randomised controlled trial. Lancet 2021;396:1941–2084. https://doi.org/10.1016/S0140-6736(20)32466-1.Search in Google Scholar PubMed PubMed Central

16. Waheed, S, Bayas, A, Hindi, F, Rizvi, Z, Espinosa, PS. Neurological complications of COVID-19: guillain-Barre syndrome following Pfizer COVID-19 vaccine. Cureus 2021;13:e13426–30. https://doi.org/10.7759/cureus.13426.Search in Google Scholar PubMed PubMed Central

17. Sønderskov, KM, Dinesen, PT, Østergaard, SD. Sustained COVID-19 vaccine willingness after safety concerns over the Oxford-AstraZeneca vaccine. Dan Med J 2021;68:A03210292.Search in Google Scholar

18. MacNeil, JR, Su, JR, Broder, KR, Guh, AY, Gargano, JW, Wallace, M, et al.. Updated recommendations from the Advisory Committee on Immunization Practices for use of the Janssen (Johnson & Johnson) COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome among vaccine recipients—United States, April 2021. Morb Mortal Wkly Rep 2021;70:651. https://doi.org/10.15585/mmwr.mm7017e4.Search in Google Scholar PubMed PubMed Central

19. Román, GC, Gracia, F, Torres, A, Palacios, A, Gracia, K, Harris, D. Acute transverse myelitis (ATM): clinical review of 43 patients with COVID-19-associated ATM and 3 post-vaccination ATM serious adverse events with the ChAdOx1 nCoV-19 vaccine (AZD1222). Front Immunol 2021;12:879. https://doi.org/10.3389/fimmu.2021.653786.Search in Google Scholar PubMed PubMed Central

20. Zuhorn, F, Graf, T, Klingebiel, R, Schäbitz, WR, Rogalewski, A. Postvaccinal encephalitis after ChAdOx1 nCov-19. Ann Neurol 2021;90:506–11. https://doi.org/10.1002/ana.26182.Search in Google Scholar PubMed PubMed Central

21. Wolf, ME, Luz, B, Niehaus, L, Bhogal, P, Bäzner, H, Henkes, H. Thrombocytopenia and intracranial venous sinus thrombosis after “COVID-19 vaccine AstraZeneca” exposure. J Clin Med 2021;10:1599. https://doi.org/10.3390/jcm10081599.Search in Google Scholar PubMed PubMed Central

22. Prasad, A, Hurlburt, G, Podury, S, Tandon, M, Kingree, S, Sriwastava, S. A novel case of bifacial diplegia variant of guillain-Barré syndrome following Janssen COVID-19 vaccination. Neurol Int 2021;13:404–9. https://doi.org/10.3390/neurolint13030040.Search in Google Scholar PubMed PubMed Central

23. Brosh-Nissimov, T, Sorek, N, Yeshayahu, M, Zherebovich, I, Elmaliach, M, Cahan, A, et al.. Oropharyngeal shedding of herpesviruses before and after BNT162b2 mRNA vaccination against COVID-19. Vaccine 2021;39:5729–31.10.1016/j.vaccine.2021.08.088Search in Google Scholar PubMed PubMed Central

24. Garg, I, Shekhar, R, Sheikh, AB, Pal, S. COVID-19 vaccine in pregnant and lactating women: a review of existing evidence and practice guidelines. Infect Dis Rep 2021;13:685–99.10.3390/idr13030064Search in Google Scholar PubMed PubMed Central

25. Queler, SC, Towbin, AJ, Milani, C, Whang, J, Sneag, DB. Parsonage-Turner syndrome following COVID-19 vaccination: MR neurography. Radiology 2022;302:84–7.10.1148/radiol.2021211374Search in Google Scholar PubMed PubMed Central

26. FDA News Release. Coronavirus (COVID-19) Update: July 13, 2021. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-july-13-2021. [Accessed 13 July 2021].Search in Google Scholar

27. Hause, AM, Gee, J, Johnson, T, Jazwa, A, Marquez, P, Miller, E, et al.. Anxiety-related adverse event clusters after Janssen COVID-19 vaccination—five US mass vaccination sites, April 2021. CDC 2021;70:685–8.10.15585/mmwr.mm7018e3Search in Google Scholar

28. Bhandari, B, Rayamajhi, G, Lamichhane, P, Shenoy, AK. Adverse events following immunization with COVID-19 vaccines: a narrative review. Biomed Res Int 2022.10.1155/2022/2911333Search in Google Scholar PubMed PubMed Central

29. World Health Organization. MODULE 3: Adverse events following immunization MODULE 3 Adverse events following immunization nd. Available from: https://www. who. int/vaccine_safety/initiative/tech_support. Part-3. pdf.Search in Google Scholar

30. Castelli, GP, Pognani, C, Sozzi, C, Franchini, M, Vivona, L. Cerebral venous sinus thrombosis associated with thrombocytopenia post-vaccination for COVID-19. Crit Care 2021;25:1–2. https://doi.org/10.1186/s13054-021-03572-y.Search in Google Scholar PubMed PubMed Central

31. Clark, RT, Johnson, L, Billotti, J, Foulds, G, Ketels, T, Heard, K, et al.. Early outcomes of bivalirudin therapy for thrombotic thrombocytopenia and cerebral venous sinus thrombosis after Ad26. COV2. S vaccination. Ann Emerg Med 2021;78:511–4. https://doi.org/10.1016/j.annemergmed.2021.04.035.Search in Google Scholar PubMed PubMed Central

32. Ryan, E, Benjamin, D, McDonald, I, Barrett, A, McHugh, J, Ryan, K, et al.. AZD1222 vaccine-related coagulopathy and thrombocytopenia without thrombosis in a young female. Br J Haematol 2021;194:547–56. https://doi.org/10.1111/bjh.17530.Search in Google Scholar PubMed PubMed Central

33. George, G, Friedman, KD, Curtis, BR, Lind, SE. Successful treatment of thrombotic thrombocytopenia with cerebral sinus venous thrombosis following Ad26. COV2. S vaccination. Am J Hematol 2021;96:E301–3. https://doi.org/10.1002/ajh.26237.Search in Google Scholar PubMed

34. Gattringer, T, Gressenberger, P, Gary, T, Wölfler, A, Kneihsl, M, Raggam, RB. Successful management of vaccine-induced immune thrombotic thrombocytopenia-related cerebral sinus venous thrombosis after ChAdOx1 nCov-19 vaccination. Stroke Vasc Neurol 2021;7:e001142. https://doi.org/10.1136/svn-2021-001142.Search in Google Scholar PubMed PubMed Central

35. Varona, JF, García-Isidro, M, Moeinvaziri, M, Ramos-López, M, Fernández-Domínguez, M. Primary adrenal insufficiency associated with Oxford-AstraZeneca ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia (VITT). Eur J Intern Med 2021;91:90–2. https://doi.org/10.1016/j.ejim.2021.06.025.Search in Google Scholar PubMed PubMed Central

36. Pottegård, A, Lund, LC, Karlstad, Ø, Dahl, J, Andersen, M, Hallas, J, et al.. Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. Bmj 2021;373:n1114–24.10.1136/bmj.n1114Search in Google Scholar PubMed PubMed Central

37. Krzywicka, K, Heldner, MR, Sánchez van Kammen, M, van Haaps, T, Hiltunen, S, Silvis, SM, et al.. Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European Medicines Agency. Eur J Neurol 2021;28:3656–62. https://doi.org/10.1111/ene.15029.Search in Google Scholar PubMed PubMed Central

38. Mehta, PR, Mangion, SA, Benger, M, Stanton, BR, Czuprynska, J, Arya, R, et al.. Cerebral venous sinus thrombosis and thrombocytopenia after COVID-19 vaccination–A report of two UK cases. Brain Behav Immun 2021;95:514–7. https://doi.org/10.1016/j.bbi.2021.04.006.Search in Google Scholar PubMed PubMed Central

39. Cao, L, Ren, L. Acute disseminated encephalomyelitis after severe acute respiratory syndrome coronavirus 2 vaccination: a case report. Acta Neurol Belg 2021;122:793–5. https://doi.org/10.1007/s13760-021-01608-2.Search in Google Scholar PubMed PubMed Central

40. Ozonoff, A, Nanishi, E, Levy, O. Bell’s palsy and SARS-CoV-2 vaccines—an unfolding story–Authors’ reply. Lancet Infect Dis 2021;21:1211–2. https://doi.org/10.1016/s1473-3099(21)00323-6.Search in Google Scholar

41. Águila-Gordo, D, Flores-Barragán, JM, Ferragut-Lloret, F, Portela-Gutierrez, J, LaRosa-Salas, B, Porras-Leal, L, et al.. Acute myelitis and SARS-CoV-2 infection. A new etiology of myelitis? J Clin Neurosci 2020;80:280–1. https://doi.org/10.1016/j.jocn.2020.07.074.Search in Google Scholar PubMed PubMed Central

42. GÜLER, MA, Keskin, F, Hüseyin, TA. Acute myelitis secondary to COVID-19 in an adolescent: causality or coincidence? New Trend Med Sci 2020;1:132–6.Search in Google Scholar

43. Knoll, MD, Wonodi, C. Oxford–AstraZeneca COVID-19 vaccine efficacy. Lancet 2021;397:72–4. https://doi.org/10.1016/s0140-6736(20)32623-4.Search in Google Scholar PubMed PubMed Central

44. Graber, JJ, Allie, SR, Mullen, KM, Jones, MV, Wang, T, Krishnan, C, et al.. Interleukin-17 in transverse myelitis and multiple sclerosis. J Neuroimmunol 2008;196:124–32. https://doi.org/10.1016/j.jneuroim.2008.02.008.Search in Google Scholar PubMed

45. Vera-Lastra, O, Medina, G, Cruz-Dominguez, MD, Jara, LJ, Shoenfeld, Y. Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld’s syndrome): clinical and immunological spectrum. Expet Rev Clin Immunol 2013;9:361–73. https://doi.org/10.1586/eci.13.2.Search in Google Scholar PubMed

46. Sotoca, J, Rodríguez-Álvarez, Y. COVID-19-associated acute necrotizing myelitis. Neurol Neuroimmunol NeuroIn 2020;7. https://doi.org/10.1212/nxi.0000000000000803.Search in Google Scholar PubMed PubMed Central

47. Chakaya, J, Khan, M, Ntoumi, F, Aklillu, E, Fatima, R, Mwaba, P, et al.. Global tuberculosis report 2020–reflections on the global TB burden, treatment and prevention efforts. Int J Infect Dis 2021;113:S7–12. https://doi.org/10.1016/j.ijid.2021.02.107.Search in Google Scholar PubMed PubMed Central

48. Peitersen, E. Bell’s palsy: the spontaneous course of 2, 500 peripheral facial nerve palsies of different etiologies. Acta Otolaryngol 2002;122:4–30. https://doi.org/10.1080/000164802320401694.Search in Google Scholar

49. Kempf, W, Meylan, P, Gerber, S, Aebi, C, Agosti, R, Büchner, S, et al.. Swiss recommendations for the management of varicella zoster virus infections. Swiss medical weekly 2007;137:239–51.Search in Google Scholar

50. Santosh, AB, Muddana, K. Viral infections of oral cavity. J Fam Med Prim Care 2020;9:36. https://doi.org/10.4103/jfmpc.jfmpc_807_19.Search in Google Scholar PubMed PubMed Central

51. Lapenna, F, Lochi, L, De Mari, M, Iliceto, G, Lamberti, P. Post-vaccinic opsoclonus–myoclonus syndrome: a case report. Park Relat Disord 2000;6:241–2. https://doi.org/10.1016/s1353-8020(00)00020-1.Search in Google Scholar PubMed

52. Ewer, KJ, Barrett, JR, Belij-Rammerstorfer, S, Sharpe, H, Makinson, R, Morter, R, et al.. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat Med 2021;27:270–8.10.1038/s41591-020-01194-5Search in Google Scholar PubMed

53. Hervé, C, Laupèze, B, Del Giudice, G, Didierlaurent, AM, Tavares Da Silva, F. The how’s and what’s of vaccine reactogenicity. Npj Vaccines 2019;4:1. https://doi.org/10.1038/s41541-019-0132-6.Search in Google Scholar PubMed PubMed Central

54. Mehta, P, McAuley, DF, Brown, M, Sanchez, E, Tattersall, RS, Manson, JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet 2020;395:1033–4.10.1016/S0140-6736(20)30628-0Search in Google Scholar PubMed PubMed Central

55. Blackburn, KM, Wang, C. Post-infectious neurological disorders. Therap Adv Neurol Dis 2020;13:1–17. https://doi.org/10.1177/1756286420952901.Search in Google Scholar PubMed PubMed Central

56. Boziki, MK, Mentis, A-FA, Shumilina, M, Makshakov, G, Evdoshenko, E, Grigoriadis, N. COVID-19 immunopathology and the central nervous system: implications for multiple sclerosis and other autoimmune diseases with associated demyelination. Brain Sci 2020;10:345. https://doi.org/10.3390/brainsci10060345.Search in Google Scholar PubMed PubMed Central

57. Poser, CM. Román GC, Emery ES 3rd. Recurrent disseminated vasculomyelinopathy. Arch Neurol 1978;35:166–70. https://doi.org/10.1001/archneur.1978.00500270048010.Search in Google Scholar PubMed

58. Mancera-Páez, O, Román, GC, Pardo-Turriago, R, Rodríguez, Y, Anaya, JM. Concurrent Guillain- Barré syndrome, transverse myelitis and encephalitis postZika: a case report and review of the pathogenic role of multiple arboviral immunity. J Neurol Sci 2018;395:47–53. https://doi.org/10.1016/j.jns.2018.09.028.Search in Google Scholar PubMed

59. Sharifian-Dorche, M, Bahmanyar, M, Sharifian-Dorche, A, Mohammadi, P, Nomovi, M, Mowla, A. Vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID-19 vaccination; a systematic review. J Neurol Sci 2021;428:117607. https://doi.org/10.1016/j.jns.2021.117607.Search in Google Scholar PubMed PubMed Central

60. MacNeil, JR, Su, JR, Broder, KR, Guh, AY, Gargano, JW, Wallace, M, et al.. Updated recommendations from the Advisory Committee on Immunization Practices for use of the Janssen (Johnson & Johnson) COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome among vaccine recipients—United States, April 2021. Morb Mortal Wkly Rep 2021;70:651. https://doi.org/10.15585/mmwr.mm7017e4.Search in Google Scholar PubMed PubMed Central

61. Klein, NP, Lewis, N, Goddard, K, Fireman, B, Zerbo, O, Hanson, KE, et al.. Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA 2021;326:1390–9. https://doi.org/10.1001/jama.2021.15072.Search in Google Scholar PubMed PubMed Central

62. Pagenkopf, C, Südmeyer, M. A case of longitudinally extensive transverse myelitis following vaccination against Covid-19. J Neuroimmunol 2021;358:577606.10.1016/j.jneuroim.2021.577606Search in Google Scholar PubMed PubMed Central

63. Gao, JJ, Tseng, HP, Lin, CL, Shiu, JS, Lee, MH, Liu, CH. Acute transverse myelitis following COVID-19 vaccination. Vaccines 2021;9:1008. https://doi.org/10.3390/vaccines9091008.Search in Google Scholar PubMed PubMed Central

64. Notghi, AA, Atley, J, Silva, M. Lessons of the month 1: longitudinal extensive transverse myelitis following AstraZeneca COVID-19 vaccination. Clin Med 2021;21:e535. https://doi.org/10.7861/clinmed.2021-0470.Search in Google Scholar PubMed PubMed Central

65. Nejad, JH, Heiat, M, Hosseini, MJ, Allahyari, F, Lashkari, A, Torabi, R, et al.. Guillain-Barré syndrome associated with COVID-19: a case report study. J Neurovirol 2021;27:802–5. https://doi.org/10.1007/s13365-021-00984-y.Search in Google Scholar PubMed PubMed Central

66. Rostami, Z, Cegolon, L, Jafari, NJ, Gholami, N, Mousavi, SV, Allahyari, F, et al.. A rare case of coexistence of Wegener’s granulomatosis and pulmonary tuberculosis with subsequent development of thrombosis of the cerebral veins. BMC Infect Dis 2021;21:1–8. https://doi.org/10.1186/s12879-021-06583-w.Search in Google Scholar PubMed PubMed Central

Received: 2022-04-19
Accepted: 2022-08-09
Published Online: 2022-09-12
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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