SARS-CoV-2 infection and risk of subsequent demyelinating diseases: national register-based cohort study

Demyelinating diseases including multiple sclerosis are associated with prior infectious exposures, so we assessed whether SARS-CoV-2 infection is associated with subsequent diagnoses of non-multiple sclerosis demyelinating diseases and multiple sclerosis. All residents of Sweden aged 3-100 years were followed between 1 January 2020 and 30 November 2022, excluding those with demyelinating disease prior to 2020, comprising 9 959 818 individuals divided into uninfected and those who were infected were categorized into those with and without hospital admission for the infection as a marker of infection severity. Cox regression assessed the risk of two separate outcomes: hospital diagnosed non-multiple sclerosis demyelinating diseases of the CNS and multiple sclerosis. The exposures were modelled as time-varying covariates (uninfected, infection without hospital admission and infected with hospital admission). Hospital admission for COVID-19 was associated with raised risk of subsequent non-multiple sclerosis demyelinating disease, but only 12 individuals had this outcome among the exposed, and of those, 7 has an unspecified demyelinating disease diagnosis. Rates per 100 000 person-years (and 95% confidence intervals) were 3.8 (3.6-4.1) among those without a COVID-19 diagnosis and 9.0 (5.1-15.9) among those admitted to hospital for COVID-19, with an adjusted hazard ratio and (and 95% confidence interval) of 2.35 (1.32-4.18, P = 0.004). Equivalent associations with multiple sclerosis (28 individuals had this outcome among the exposed) were rates of 9.5 (9.1-9.9) and 21.0 (14.5-30.5) and an adjusted hazard ratio of 2.48 (1.70-3.61, P < 0.001). Only a small number of non-multiple sclerosis demyelinating disease diagnoses were associated with hospital admission for COVID-19, and while the number with multiple sclerosis was somewhat higher, longer duration of follow-up will assist in identifying whether the associations are causal or due to shared susceptibility or surveillance bias, as these diseases can have long asymptomatic and prodromal phases.