A pair of new studies are building on a growing hypothesis that the neurological disease multiple sclerosis (MS) can be triggered by viral infections in a person’s teenage years. The research indicates serious adolescent infections such as glandular fever are associated with higher rates of MS diagnoses, and concerns are being raised as to whether the current COVID-19 pandemic could lead to a surge in MS cases in the future.
MS is most commonly diagnosed in a person’s late 20s, brought on by a number of genetic and environmental factors. For several decades researchers have detected an association between herpes virus infections and MS, with many hypothesizing the virus can trigger the onset of the disease.
While few would argue viral infections are the sole cause of MS, increasing evidence proposes a severe viral infection in a person’s teenage years can bring on the disease in those already susceptible. The idea is the viral infection prompts an excessive immune response that begins the process of immune cells damaging nerves in the brain. And once this process starts it progressively gets worse until MS symptoms become apparent years after the acute viral infection.
Two new studies are offering more evidence viral infections can trigger MS by looking at health records from several million people born in Sweden between 1970 and 1994. The first study broadly investigated correlations between hospital-diagnosed infections before the age of 20 and MS diagnoses after the age of 20.
Here the researchers determined infections before the age of 11 were not associated with any subsequent MS diagnosis, however, infections between the ages of 11 and 19 were consistently linked with heightened risk of MS.
Infections such as mononucleosis, pneumonia, or those generally affecting the central nervous system accounted for the greatest increases in MS risk. But other kinds of adolescent infections could also be seen to play a role in increasing risk.
Even though glandular fever may be triggering MS, most often around puberty, it can be many years before MS is diagnosed
The second study, from the same team of researchers working with the same dataset, more specifically focused on the relationship between MS and infectious mononucleosis, also known as glandular fever, a disease caused by the Epstein-Barr virus. The goal of this study was to work out whether the viral infection was more prominent in teenagers who were already susceptible to MS because of a pre-existing immune system abnormality, or whether the infection actively triggered the onset of MS.
“To confirm that infections are a true risk factor for MS, triggering the MS disease process, our latest study compared siblings in the same family,” explains Scott Montgomery, an author on both new studies. “Siblings share much of their genetic make-up and have similar family lives. If one sibling develops glandular fever and goes on to develop MS, while the other does not develop glandular fever and does not develop MS, that would suggest that it is the glandular fever rather than any genetic predisposition that led to the MS. On the other hand, if only one developed glandular fever but they both later developed MS, that would suggest a genetic predisposition was to blame.”
The researchers confidently conclude the viral infection does play a significant role in triggering MS, independent of any heritable factor. The data also indicated the greatest risk for MS came with infections seen between the ages of 11 and 15.
“Even though glandular fever may be triggering MS, most often around puberty, it can be many years before MS is diagnosed,” writes Montgomery in a piece for The Conversation. “Many who had the infection between ages 11 and 15 years did not have an MS diagnosis until after they were 30. This is because the damage to the brain caused by MS develops slowly until it makes someone sick enough to receive a diagnosis of MS.”
The idea of a virus triggering the onset of a neurological disease appearing years, or even decades, after the acute infection is not new. In the 1950s several researchers speculated microbial infections to be the cause of many neurodegenerative diseases. The hypothesis was known as “slow virus diseases.” One prominent proposal considered Alzheimer’s disease to be caused by the herpes simplex virus.
So is there a big pandemic-related elephant in the room? If severe viral infections can increase a person’s risk for later-life neurological disease then what can we expect in the future from the current wave of SARS-CoV-2 infections?
Late last year a team of neuroscientists at the Florey Institute of Neuroscience & Mental Health penned an article warning a "silent wave" of Parkinson’s disease may follow the COVID-19 pandemic. Pointing out Parkinson’s disease is likely caused by a “mosaic” of environmental and genetic factors, the researchers speculated the ability of SARS-CoV-2 to enter the brain could mean it triggers neuroinflammation that can increase a person’s risk of developing the neurological disease.
Much like the MS/viral infection hypothesis, the researchers do not claim a SARS-CoV-2 infection will cause Parkinson’s, but instead hypothesize it acts like a trigger for the disease in those already susceptible.
As Montgomery makes clear in his MS research, “Only a few people who have relatively serious infections in adolescence will go on to have MS (in most instances much lower than 1%), as other factors, including genetic susceptibility, are also needed for the disease to develop.”
But will the sheer volume of people infected with SARS-CoV-2 be enough to trigger a spike in new MS cases over the next ten to 20 years?
A recently published review article from a large team of neuroscientists outlines the ways SARS-CoV-2 could influence the development of MS, ultimately concluding, "it is plausible that the immune response following SARS-CoV-2 infection could contribute to neuroinflammation in genetically susceptible people, precipitating MS onset or even impacting on progression."
An open letter from a pair of Cairo University researchers presents a similar argument, indicating the pandemic could increase the incidence of the disease in the coming years. The researchers also propose the coming years will offer rich opportunities to study the way viral infections can influence autoimmune central nervous system diseases.
Ultimately, the relationship between adolescent viral infection and MS is still unclear. Montgomery notes his research detected a minimum span of five years between viral infection and MS diagnosis, but often that stretch was even longer.
"Our study provides further evidence that adolescence is a period of heightened susceptibility to exposures linked with MS risk and that there can be many years between exposure and MS diagnosis," writes Montgomery. "These results help us to better understand the types of exposures that may increase the risk of MS. It may be worthwhile considering MS as a potential diagnosis in someone displaying neurological symptoms if they had a serious infection in adolescence."
The new studies were published in the journals JAMA Network Open and Brain.
