Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host’s genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host’s response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.

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Epstein-Barr Virus Versus Novel Coronavirus-Induced Hemophagocytic Lymphohistocytosis: The Uncharted Waters

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620950107 ◽

2020 ◽

Vol 8 ◽

pp. 232470962095010 ◽

Cited By ~ 1

Author(s):

Rawan Amir ◽

Asim Kichloo ◽

Jagmeet Singh ◽

Ravinder Bhanot ◽

Michael Aljadah ◽

...

Keyword(s):

Bacterial Infections ◽

Epstein Barr Virus ◽

Genetic Mutations ◽

High Grade ◽

The Novel ◽

Barr Virus ◽

First Case ◽

Epstein Barr ◽

Virus Versus ◽

Novel Coronavirus

Hemophagocytic lymphohistocytosis (HLH) is a hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, and pancytopenia. It may be associated with genetic mutations or viral/bacterial infections, most commonly Epstein-Barr virus (EBV) and cytomegalovirus. As for the novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19 (coronavirus disease-2019), the cytokine storm it triggers can theoretically lead to syndromes similar to HLH. In this article, we report a case of a 28-year-old female who presented with high-grade fevers, found to have both SARS-CoV-2 and EBV infections, and eventually began to show signs of early HLH. To our knowledge, this is the first case reported in literature that raises the possibility of SARS-CoV-2–related HLH development.

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Oligoclonal IgGs against DNA, Histones, and Myelin Basic Protein in the Cerebrospinal Fluid of Patients with Multiple Sclerosis

Austin Journal of Clinical Immunology ◽

10.26420/austinjclinimmunol.2021.1043 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Kostrikina IA ◽

◽

Granieri E ◽

Nevinsky GA ◽

◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Myelin Basic Protein ◽

Basic Protein ◽

Main Role ◽

Barr Virus ◽

The Central Nervous System ◽

Epstein Barr ◽

Ms Pathogenesis ◽

Myelin Proteolipid

Multiple Sclerosis (MS) is known as a chronic demyelinating pathology of the central nervous system. The most accepted MS pathogenesis theory assigns the main role to demyelination of myelin-proteolipid shells due to inflammationrelated with autoimmune reactions. One of the features of MS patients is the enhanced synthesis of oligoclonal IgGs in the bone marrow Cerebrospinal Fluid (CSF). By antigen-specific immunoblotting after isoelectrofocusing of IgGs, oligoclonal IgGs in CSF of MS patients were revealed only against the components of Epstein-Barr virus and Chlamydia. However, there was still unknown to which human auto-antigens in MS patients oligoclonal IgGs may be produced. Here it was first shown that in the CSF of a narrow percentage of MS patients, oligoclonal IgGs are produced against their own antigens: DNA (24% patients), histones (20%), and myelin basic protein (12%). At the same time, the CSF of MS patients contains a very large amount of auto-IgGs-abzymes that hydrolyze DNA, histones, and myelin basic protein, which during isofocusing, are distributed throughout the gel from pH 3 to 10. It is concluded that these multiple IgGs-abzymes, which are dangerous to humans since stimulate development of MS, in the main are non-oligoclonal antibodies.

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A Survey of Serum Antibodies to Eight Common Viruses in Psychiatric Patients

The British Journal of Psychiatry ◽

10.1192/bjp.147.2.137 ◽

1985 ◽

Vol 147 (2) ◽

pp. 137-144 ◽

Cited By ~ 29

Author(s):

D. J. King ◽

S. J. Cooper ◽

J. A. P. Earle ◽

S. J. Martin ◽

N. V. McFerran ◽

...

Keyword(s):

Viral Infections ◽

Psychiatric Patients ◽

Serum Antibody ◽

Later Life ◽

Barr Virus ◽

Neurotropic Viruses ◽

Antibody Titres ◽

The Central Nervous System ◽

Epstein Barr ◽

Simplex Virus

SummarySerum antibody titres to eight neurotropic viruses were measured by enzyme immunoassay in 450 psychiatric in-patients and 143 controls. A seasonal variation in schizophrenic births was observed, with a peak incidence between March and April. Both herpes simplex virus and cytomegalovirus antibody titres correlated with age and, when this was controlled for, no significant differences emerged between any patient group and the controls. Mumps antibody titres were significantly lower in patients with mental subnormal and neurosis or personality disorder; measles and rubella antibody titres were lower in male but not female mentally handicapped patients; males had lower antibody titres to mumps, cytomegalovirus and Epstein-Barr virus than females in all groups. A decrease in mumps antibody titres was also found in schizophrenics if the medication factor was excluded. These low antibody titres may indicate an impaired immune response. Thus perinatal or childhood subclinical viral infections of the central nervous system, particularly of mumps, might lead to a range of possible psychiatric outcomes in later life.

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The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms20020303 ◽

2019 ◽

Vol 20 (2) ◽

pp. 303 ◽

Cited By ~ 11

Author(s):

Rachael Tarlinton ◽

Timur Khaibullin ◽

Evgenii Granatov ◽

Ekaterina Martynova ◽

Albert Rizvanov ◽

...

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Large Scale ◽

Motor Impairment ◽

Endogenous Retrovirus ◽

Barr Virus ◽

Scale Population ◽

Epidemiological Risk ◽

The Central Nervous System ◽

Epstein Barr

Multiple sclerosis (MS) is a chronic debilitating inflammatory disease of unknown ethology targeting the central nervous system (CNS). MS has a polysymptomatic onset and is usually first diagnosed between the ages of 20–40 years. The pathology of the disease is characterized by immune mediated demyelination in the CNS. Although there is no clinical finding unique to MS, characteristic symptoms include sensory symptoms visual and motor impairment. No definitive trigger for the development of MS has been identified but large-scale population studies have described several epidemiological risk factors for the disease. This list is a confusing one including latitude, vitamin D (vitD) levels, genetics, infection with Epstein Barr Virus (EBV) and endogenous retrovirus (ERV) reactivation. This review will look at the evidence for each of these and the potential links between these disparate risk factors and the known molecular disease pathogenesis to describe potential hypotheses for the triggering of MS pathology.

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Translational Mini-Review Series on B cell subsets in disease. B cells in multiple sclerosis: drivers of disease pathogenesis and Trojan horse for Epstein-Barr virus entry to the central nervous system?

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.2011.04446.x ◽

2011 ◽

Vol 167 (1) ◽

pp. 1-6 ◽

Cited By ~ 23

Author(s):

U.-C. Meier ◽

G. Giovannoni ◽

J. S. Tzartos ◽

G. Khan

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Epstein Barr Virus ◽

Virus Entry ◽

Disease Pathogenesis ◽

Barr Virus ◽

The Central Nervous System ◽

Epstein Barr ◽

B Cell Subsets

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Deficiency of CD8+ effector memory T cells is an early and persistent feature of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458514536252 ◽

2014 ◽

Vol 20 (14) ◽

pp. 1825-1832 ◽

Cited By ~ 33

Author(s):

Michael P Pender ◽

Peter A Csurhes ◽

Casey MM Pfluger ◽

Scott R Burrows

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

T Cell ◽

Epstein Barr Virus ◽

Clinical Course ◽

Effector Memory ◽

Barr Virus ◽

Effector Memory T Cells ◽

The Central Nervous System ◽

Epstein Barr

Background: Patients with multiple sclerosis (MS) have a deficiency of circulating CD8+ T cells, which might impair control of Epstein–Barr virus (EBV) and predispose to MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. Based on the expression of CD45RA and CD62L, CD4+ T cells and CD8+ T cells can be subdivided into four subsets with distinct homing and functional properties, namely: naïve, central memory, effector memory (EM) and effector memory re-expressing CD45RA (EMRA) cells. Objective: Our aim was to determine which memory subsets are involved in the CD8+ T cell deficiency and how these relate to clinical course. Methods: We used flow cytometry to analyze the memory phenotypes of T cells in the blood of 118 MS patients and 112 healthy subjects. Results: MS patients had a decreased frequency of EM (CD45RA–CD62L–) and EMRA (CD45RA+CD62L–) CD8+ T cells, which was present at the onset of disease and persisted throughout the clinical course. The frequencies of CD4+ EM and EMRA T cells were normal. Conclusion: Deficiency of effector memory CD8+ T cells is an early and persistent feature of MS and might underlie the impaired CD8+ T cell control of EBV.

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Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

Science ◽

10.1126/science.abj8222 ◽

2022 ◽

Author(s):

Kjetil Bjornevik ◽

Marianna Cortese ◽

Brian C. Healy ◽

Jens Kuhle ◽

Michael J. Mina ◽

...

Keyword(s):

Multiple Sclerosis ◽

Epstein Barr Virus ◽

Demyelinating Disease ◽

Serum Levels ◽

Unknown Etiology ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Barr Virus ◽

The Central Nervous System ◽

Epstein Barr

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

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