EBV in Germany, is this the answer?

E

EBV, vitamin D and genetics are probably some of the most commonly reported risk factors for MS. All studies report these in terms of hazard ratios comparing occurrence in the exposed versus non-exposed individuals.

Hazard ratio (HR) = (risk of outcome in one group)/ (risk of outcome in another group)

An HR of 1 therefore means lack of association, a hazard ratio of greater than 1 suggests an increased risk, and a hazard ratio below 1 suggests a smaller risk.

In this case the HR of infectious mononucleosis (illness caused by EBV infection) being associated with MS is 1.86. That is:

  • The association with MS in those with EBV infection is 1.86 times higher of that of those without EBV.
  • The association with MS in those exposed to EBV infection is 186% of that not exposed to EBV.
  • Exposure to EBV infection increases the association with MS by 186% compared to no exposure to EBV.
  • At each time point of an observation, for every 100 cases of MS not having EBV infection, there will be 186 cases of MS for the reason of EBV.

Unlike the first few points, the last point suggests in practical terms the association is marginal.

Figure: Kaplan-Meier curves regarding the incidence of multiple sclerosis diagnosis in patients with and without infectious mononucleosis.

Now what is interesting is that when you stratify this data by age, the only age group that was significantly was driving this is the 14-20 year old age category (HR: 3.52, 95% CI: 1.00-12.37), suggesting that the association is more immediate than we think and the time lag between seroconversion and MS is short.

Make what you may of this.

Abstract

Front Immunol.2022 Aug 2;13:937583.

 doi: 10.3389/fimmu.2022.937583. eCollection 2022.

Infectious mononucleosis is associated with an increased incidence of multiple sclerosis: Results from a cohort study of 32,116 outpatients in Germany

Sven H LoosenCorinna Doege  Sven G MeuthTom LueddeKarel Kostev  Christoph Roderburg 

Background: The pathogenesis of multiple sclerosis (MS) has not yet been fully uncovered. There is increasing evidence that Epstein-Barr-Virus (EBV) infection, which affects over 90% of people during life and causes infectious mononucleosis, leads to an increased incidence of MS, and thus may play a crucial role in the pathophysiology of the disease.

Methods: Using the Disease Analyzer database (IQVIA) featuring diagnoses as well as basic medical and demographic data of outpatients from general practices in Germany, we identified a total of 16,058 patients with infectious mononucleosis that were matched to a cohort of equal size without infectious mononucleosis based on patients’ age, sex, index year and yearly consultation frequency. Incidence of MS was compared within a 10-year follow-up period.

Results: Within 10 years from the index date, the incidence of MS was 22.6 cases per 100,000 person-years among patient with infectious mononucleosis but only 11.9 cases per 100,000 person-years among individuals without infectious mononucleosis. In regression analysis, infectious mononucleosis was significantly associated with the incidence of MS (HR: 1.86, 95% CI: 1.09-3.16). Subgroup analysis revealed the strongest association between infectious mononucleosis and MS in the age group between 14 and 20 years (HR: 3.52, 95% CI: 1.00-12.37) as well as a stronger association in men compared to women.

Conclusion: Infectious mononucleosis is associated with an increased incidence of MS especially in younger individuals. Our data support the growing evidence of a decisive involvement of EBV in the currently unknown pathophysiology of MS and should trigger further research efforts to better understand and potentially prevent cases of this disabling disease in future.

About the author

Neuro Doc Gnanapavan

9 comments

  • The data comes from a database of diagnosis codes from patients. So if a patient didn’t have a documented case of an EBV infection or mononucleosis, but later was diagnosed with the more debilitating disease of MS, they would show up in the category of not adding to the association. Because a primary EBV infection may be treated with at home care, the association may be underreported. In other words, the Hazard Ratio of 1.86 may be a lower bound of the association. Responses?

    • Yes, this is a major bias of this study. Unlike the previous study in military personnel this study didn’t measure the EBV antibody levels.

      • I agree on the bias of who was infected and/or who wasn’t infected data.

        My history with infectious Mono at 14 y/o was 4 days in the hospital with severe dehydration from the severe sore throat.
        I wore my self out playing at a basketball camp the week prior, then MONO hit me hard.

        What is interesting, my Mother had MS (RIP 2005) and my older Brother as well, he is playing the denial card.

        Anyway, if the Mono theory is correct, then my mom and my brother are outliers,
        I don’t remember my brother or my mother infected with MONO at the same time as me, but earlier infection in life is possible.

        What are the odds my only brother, our mother, and I have MS.
        EBV may be the smoking gun, and I am ready like all others to find the MS cause, then possible treatment if we could come to a conclusion. EBV has been studied since the 90’s, still waiting for the result. Seems like the researchers are dragging their heals for job security imo, repeat, next.

        I also blame heavy agriculture chemicals sprayed that we live around, a diesel spill superfund site, Pentax pollution/superfund site nearby, and 3 nuclear weapons detonated.

        My mother lived through the bomb in 1945, and 1960’s.

        Feds won’t give us the time of day, they never apologized or compensated anyone in NM after the first atomic bomb in NM, USA 1945, unbelievably a crime.

        For 3 weeks the Feds kept the detonation, including the awful radiation poison a secret until after the first bomb was dropped on Nagasaki, Japan 8-1945.
        Thus the majority of New Mexicans USA breathed radiation, ate, drank, wore radiated clothes and played in the radiation fallout with no indication the bomb was atomic, not ammo dump explosion, they lied.

        Thousands of New Mexicans are suffering today, including me, and waiting for apology and compensation.

        We damaged our land thousands of times more than 2 Japanese WW2 atomic bombs. USA pas for Japanese radiation studies then and now, NM was left holding the bag of poison, with zero studies, what a joke on all Americans.

        49 states in the USA are damaged by the Atomic bomb race, these states have either one or more radiated super fund site emitting radiation to date, other states equally damaged are NM, NY, Colorado, NV, WA, CA, and a few others.

        • Primary EBV infection doesn’t always present as infectious mononucleosis. Most primary EBV infections occur in childhood and are not accompanied by significant symptoms. But primary EBV infection leads to lifelong persistent (latent) infection with EBV. So when you say that your mother and brother didn’t have mononucleosis, it doesn’t mean that they were not infected with EBV.

          I would also push back against your statement that researchers are “dragging their heels” for job security reasons. We try our best with the limited resources that we have. Research over the last 30 years has led to new, amazing treatments that were frankly not available before. But I can also imagine your frustration with the seemingly slow pace of research, especially when you are suffering every day.

        • Radiation causes cancer not AI disease..
          sorry this is really not up for discussion.

          Problem is with EBV there is no treatment for it. For chronic active EBV only treatment is hsct.

  • We have known the ‘mononucleosis’ risk factor for MS for the past 40 years. This ‘confirms’ Compton’s paper, and adds a few details. Things in MS research go round and round and round.
    You equate and substitute ‘EBV infection’ in your observations for ‘mononucleosis’ and as you are well aware, the immune syndrome mono has a diversity of ’causes’. This obscures a key question, what is the mechanism of mononucleosis and its genetics? Lurking beneath the surface are immune susceptibility mechanisms that can account for these associations, but do not of necessity mean ‘a direct cause’ There are still red herrings swimming in the pool!

    • If your question is around the subversive nature of viruses and host genetics that make them susceptible then I’ve not heard of any papers looking at this particularly with EBV. HSV (Herpes simplex 1) on the other hand has been studied in the past and linked to MHC class 1 genes specifically the cytotoxic cells – cytotoxic T lymphocyte and Natural Killer cells. Whether the same may apply to EBV is not known.

        • or here we go again, around and around, next, repeat. Never ending research to no where, we need results yesterday or now PLEASE.

          We need more leaders to step up to get results, we are suffering 10/10 out here, ms sucks badly.

          Thousands of MS patients are ready for the EBV vaccine or anti-viral therapy, lets go.
          Dr’s will prescribe antibiotics all day long, but won’t treat the EBV. When A light at the end of the tunnel is shining, let us not check if this is the way out of this MS hell.

          Uggh.

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