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.
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.
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
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.