To Örebro University

Background: Severe acute infections are implicated in MS aetiology. Adolescence may represent a period of heightened susceptibility, with several years of asymptomatic/prodromal disease activity before an MS diagnosis. Infections may also be associated with MS exacerbations or severity.

Objectives: To assess if hospital-treated infections during adolescence or earlier childhood are associated with MS risk. To determine if SARS-CoV-2 infection in people with MS resulted in increased risk of subsequent hospital admission for MS.

Methods: Swedish registers provided information on 2,422,969 people born between 1970 and 1994 (with follow-up to 2014). The association of hospital-treated infections before age 20 years with MS risk was assessed using Cox regression. Registers also provided information on all Swedish residents with MS in December 2019 (n=20,237), with follow-up to September 2022. Cox regression assessed whether SARS-CoV-2 infections (modelled as time-dependent covariates) were associated with hospital admission for MS, with adjustment including for number of hospital admissions since 2015 prior to infection and Charlson comorbidity index.

Results: Some, but not all, serious bacterial or viral infections in adolescence but not earlier childhood, were associated raised risk of MS after age 20 years (median age at diagnosis 29.7 years), including respiratory infections, with an adjusted hazard ratio (and 95% confidence interval) of 1.54 (1.30-1.83). The association with respiratory infections was not explained by prior infectious mononucleosis, which was also associated with MS risk: 3.19 (2.29-4.46) Among those with MS in 2019, hospital admission for SARS-CoV-2 infection was associated with increased risk of subsequent admission for MS (typically >50 days later): 2.06 (1.18, 3.60), most notably among women.

Conclusion: Severe respiratory infections in adolescence are associated with increased MS diagnosis risk, often more than 10 years later. SARS-CoV-2 treated in hospital is associated with increased risk of hospital admission for MS, particularly among women. It is plausible that the pandemic will have short- and long-term consequences for MS risk, as well as MS severity or exacerbations.