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Comment on “The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging”

Dear Editor,

Vaccination to reduce the incidence of demyelination dis- eases is becoming an ever-increasing global health prior- ity. This is largely due to neurological manifestations and sequelae from the existing and emerging central nervous system infections that account for significant morbidity and mortality worldwide. Some existing studies support the direct and indirect effects of viral infections on the ner- vous system. The link between Epstein-Barr virus (EBV) and multiple sclerosis (MS) is supported by the elevated EBV-specific antibody levels in MS patients when com- pared to healthy controls11. Guan Y, Jakimovski D, Ramanathan M, Weinstock-Guttman B, Zivadinov R. The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging. Neural Regen Res. 2019;14(3):373-86. https://doi.org/10.4103/1673-5374.245462
https://doi.org/10.4103/1673-5374.245462...
. In contrast, we also observed the association of demyelinating diseases with COVID-19 during the pandemic of this virus22. Sahraian MA, Azimi A, Navardi S, Ala S, Moghadasi AN. Evaluation of the rate of COVID-19 infection, hospitalization and death among Iranian patients with multiple sclerosis. Mult Scler Relat Disord. 2020;46:102472. https://doi.org/10.1016/j.msard.2020.102472
https://doi.org/10.1016/j.msard.2020.102...
. Demyelinating disor- ders of the central nervous system (CNS) can appear after vaccination. Some case report studies have reported that vaccination against COVID-19 in MS patients who are in remission can cause MS relapse33. Nistri R, Barbuti E, Rinaldi V, Tufano L, Pozzilli V, Ianniello A, et al. Case report: multiple sclerosis relapses after vaccination against SARS-CoV2: a series of clinical cases. Front Neurol. 2021;12:765954. https://doi.org/10.3389/fneur.2021.765954
https://doi.org/10.3389/fneur.2021.76595...
. A 68-year-old woman with MS was diagnosed with neuromyelitis optica spectrum dis- order (NMOSD) after immunization against COVID-1944. Lohmann L, Glaser F, Möddel G, Lünemann JD, Wiendl H, Klotz L. Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report. BMC Neurology. 2022;22:185. https://doi.org/10.1186/s12883-022-02698-y
https://doi.org/10.1186/s12883-022-02698...
. In this narrative review, the potential association between vaccination and the prevention of demyelination processes caused by viruses is discussed.

In the long term, the COVID-19 epidemic may be the cause of neurological diseases in the future55. Baazaoui N, Iqbal K. COVID-19 and neurodegenerative diseases: prion-like spread and long-term consequences. J Alzheimers Dis. 2022;88(2):399-416. https://doi.org/10.3233/JAD-220105
https://doi.org/10.3233/JAD-220105...
. The exact effects of severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2) on neurological diseases are currently unknown. But different pathophysiological theories support neurode- generation with SARS-CoV-2. It is possible that COVID- 19, as an aggravating factor, is the cause of neurological symptoms or the acceleration of neurological conditions in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD)66. Krey L, Huber MK, Höglinger GU, Wegner F. Can SARS-CoV-2 infection lead to neurodegeneration and Parkinson’s disease? Brain Sci. 2021;11(12):1654. https://doi.org/10.3390/brainsci11121654
https://doi.org/10.3390/brainsci11121654...
. The importance of other viral infections in the exacerbation of neurological diseases has been investigated in recent years. However,

the possible consequences of infection with SARS-CoV-2 for triggering neurodegeneration and causing neurodegen- erative diseases are not precisely known77. Lingor P, Demleitner AF, Wolff AW, Feneberg E. SARS-CoV-2 and neurodegenerative diseases: what we know and what we don’t. J Neural Transm (Vienna). 2022;129(9):1155-67. https://doi.org/10.1007/s00702-022-02500-w
https://doi.org/10.1007/s00702-022-02500...
. We know that vaccination against SARS-CoV-2 prevents a severe course of disease55. Baazaoui N, Iqbal K. COVID-19 and neurodegenerative diseases: prion-like spread and long-term consequences. J Alzheimers Dis. 2022;88(2):399-416. https://doi.org/10.3233/JAD-220105
https://doi.org/10.3233/JAD-220105...
and can prevent the onset of neurodegenera- tive diseases.

There are less data regarding the safety or efficacy of the vaccines in patients with preexisting neurological conditions. Given the widespread effect of the COVID-19 pandemic on adults with neurological disease, the risks and benefits of vaccination must be considered for each patient. Based on COVID-19 vaccine data from the general population and extrapolations from other vaccines studies in patients with neurological diseases, statements from the American Academy of Neuromuscular and Electrodiagnostic Medicine and the National Multiple Sclerosis Society support vaccination. The risk of onset or relapse of CNS demyelination following infections against which the vaccines are aimed to protect is substantially higher and the benefits of vaccinations surpass the potential risks of CNS inflammation88. Ismail II, Salama S. A systematic review of cases of CNS demyelination following COVID-19 vaccination. J Neuroimmunol. 2022;362:577765. https://doi.org/10.1016/j.jneuroim.2021.577765
https://doi.org/10.1016/j.jneuroim.2021....
. As a link has been found between EBV and MS, other interventions that prevent EBV infection or treat EBV could also reduce the incidence of MS, for example, preventing EBV infection by vaccination at a very young age. However, EBV vaccine may have two complications. First, the vaccine itself can cause demyelinat- ing disease after vaccination against viral diseases. Second, by suppressing EBV, the role of other viruses in the pathogenesis of demyelinating disease may increase99. Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022;375(6578):296-301. https://doi.org/10.1126/science.abj8222
https://doi.org/10.1126/science.abj8222...
. Based on the existing evidence, neurologists should recommend COVID-19 vacci- nation to their patients. For those patients being treated with immunotherapies, attention should be paid to the timing of vaccination, concerning the treatment and the potential for an attenuated immune response.

Therefore, the point to keep in mind is that sometimes vac- cination itself can cause demyelinating disease.

REFERENCES

  • 1.
    Guan Y, Jakimovski D, Ramanathan M, Weinstock-Guttman B, Zivadinov R. The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging. Neural Regen Res. 2019;14(3):373-86. https://doi.org/10.4103/1673-5374.245462
    » https://doi.org/10.4103/1673-5374.245462
  • 2.
    Sahraian MA, Azimi A, Navardi S, Ala S, Moghadasi AN. Evaluation of the rate of COVID-19 infection, hospitalization and death among Iranian patients with multiple sclerosis. Mult Scler Relat Disord. 2020;46:102472. https://doi.org/10.1016/j.msard.2020.102472
    » https://doi.org/10.1016/j.msard.2020.102472
  • 3.
    Nistri R, Barbuti E, Rinaldi V, Tufano L, Pozzilli V, Ianniello A, et al. Case report: multiple sclerosis relapses after vaccination against SARS-CoV2: a series of clinical cases. Front Neurol. 2021;12:765954. https://doi.org/10.3389/fneur.2021.765954
    » https://doi.org/10.3389/fneur.2021.765954
  • 4.
    Lohmann L, Glaser F, Möddel G, Lünemann JD, Wiendl H, Klotz L. Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report. BMC Neurology. 2022;22:185. https://doi.org/10.1186/s12883-022-02698-y
    » https://doi.org/10.1186/s12883-022-02698-y
  • 5.
    Baazaoui N, Iqbal K. COVID-19 and neurodegenerative diseases: prion-like spread and long-term consequences. J Alzheimers Dis. 2022;88(2):399-416. https://doi.org/10.3233/JAD-220105
    » https://doi.org/10.3233/JAD-220105
  • 6.
    Krey L, Huber MK, Höglinger GU, Wegner F. Can SARS-CoV-2 infection lead to neurodegeneration and Parkinson’s disease? Brain Sci. 2021;11(12):1654. https://doi.org/10.3390/brainsci11121654
    » https://doi.org/10.3390/brainsci11121654
  • 7.
    Lingor P, Demleitner AF, Wolff AW, Feneberg E. SARS-CoV-2 and neurodegenerative diseases: what we know and what we don’t. J Neural Transm (Vienna). 2022;129(9):1155-67. https://doi.org/10.1007/s00702-022-02500-w
    » https://doi.org/10.1007/s00702-022-02500-w
  • 8.
    Ismail II, Salama S. A systematic review of cases of CNS demyelination following COVID-19 vaccination. J Neuroimmunol. 2022;362:577765. https://doi.org/10.1016/j.jneuroim.2021.577765
    » https://doi.org/10.1016/j.jneuroim.2021.57776
  • 9.
    Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022;375(6578):296-301. https://doi.org/10.1126/science.abj8222
    » https://doi.org/10.1126/science.abj8222
  • Funding: none.

Publication Dates

  • Publication in this collection
    28 Nov 2022
  • Date of issue
    2022

History

  • Received
    07 Sept 2022
  • Accepted
    07 Sept 2022
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