Severe COVID-19 may double risk of MS: Swedish study
Large-scale study links hospitalization to higher risk
Hospitalization for severe COVID-19 is significantly associated with a twofold higher risk of developing multiple sclerosis (MS), according to a study involving nearly the entire population of Sweden.
No increased risk of MS was found among those who tested positive for SARS-CoV-2, the virus that causes COVID-19, or received specialist care for the infection without hospitalization.
“We saw a raised risk of MS among people who had severe COVID-19,” Scott Montgomery, PhD, the study’s first author and a professor of clinical epidemiology at Örebro University, said in a university news story. Still, he said, “only an extremely small number of people who had severe COVID-19 received a subsequent MS diagnosis.”
Because “it can take up to 10 to 20 years until an MS diagnosis following a relevant exposure to the brain or spinal cord,” Montgomery said, “the extent to which serious COVID-19 is a cause of MS will become clearer in several years.”
The study, “SARS-CoV-2 infection and risk of subsequent demyelinating diseases: national register-based cohort study,” was published in Brain Communications.
Immune response and risk
In MS, the immune system mistakenly attacks the myelin sheath, the fatty, protective coating around nerve fibers that help speed electrical impulses. The resulting inflammation and damage give rise to various neurological symptoms, depending on which parts of the brain and spinal cord are affected.
One of the strongest risk factors for MS is a history of Epstein-Barr virus (EBV) infection, which raises the risk of developing the disorder by more than 30 times. It’s thought that an immune response targeting the virus can also inadvertently attack healthy brain tissue due to structural similarities between certain EBV and brain proteins.
Emerging evidence suggests an infection with SARS-CoV-2 may also set the stage for MS via a similar mechanism.
Montgomery’s team leveraged 2020-2022 sociodemographic and healthcare data on nearly 10 million people, ages 3-100 — encompassing nearly the entire population of Sweden — to investigate a potential link between SARS-CoV-2 infection and MS.
None had multiple sclerosis or other condition marked by myelin loss (demyelination) at the time of study start.
“The current study benefits from follow-up of a national population, with … recorded exposures [over time] and greater power to detect rare outcome events,” the researchers wrote.
Statistical analysis
Severe SARS-CoV-2 infection was defined as an inpatient hospital admission with a COVID-19 diagnosis. Less severe disease was marked by a positive genetic test for the virus or an outpatient visit to specialist care without hospitalization. During follow-up, 2,787 people were diagnosed with MS.
Results showed that there was an average of 21 MS cases after COVID-19 hospitalization and 9.5 cases per 100,000 person-years after a non-severe infection. Person-years account for the total number of patients and the time each patient spent in the study.
Statistical analyses showed that hospital admission for COVID-19 was significantly associated with a nearly 2.5 times higher risk of a subsequent MS diagnosis after adjusting for factors that may influence the findings. Such factors were the year of birth, sex, healthcare region in Sweden, region of birth, and co-existing diseases.
No significant link was observed between a less severe infection that did not require hospitalization and MS risk.
Overall, 28 people, with a median age of 56.7 (range: 15.9-89.9), received an MS diagnosis following hospital admission for COVID-19.
“I want to make it clear that MS is an uncommon disease and very few people in this study had an MS diagnosis linked with Covid-19,” Montgomery said.
The median time between admission and MS diagnosis was 82 days (nearly three months), ranging from five days to about two years. Most of these patients received an MS diagnosis in the first six months after hospitalization, with about one in five being diagnosed over a year after admission for COVID-19.
Majority ‘should not worry’
As the follow-up time may not be enough to capture all MS cases triggered by SARS-CoV-2 infection, these findings may represent “a minority of patients with more rapid-onset initiation” of MS-related mechanisms, the researchers wrote.
Alternatively, MS may have already begun in some people, and infection may have triggered more rapid progression such that the disease began to cause symptoms.
“There is a connection with the severity of Covid-19,” Montgomery added. “More serious Covid-19, is associated with greater risk MS, possibly uncovering latent MS.”
The team found a similar association between hospital admission for COVID-19 and the risk of a diagnosis for a non-MS demyelinating disease.
Sill, “since the majority of people who were infected will not develop diseases such as MS, they should not worry,” Montgomery said. Those with MS symptoms, however, should “seek medical advice,” as “the earlier patients with MS are treated, the better quality of life they will have, because treatments delay the worsening of the disease.”
“If we can follow the patient group that has been admitted to hospital for severe Covid-19 and identify diseases that are more likely to develop subsequently, we may be able to monitor for these diseases and hopefully help patients in a timely manner,” Montgomery said.
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