Hospital-treated infections and the risk and prognosis of amyotrophic lateral sclerosis: A population-based study

Infection has been suspected as a risk factor for amyotrophic lateral sclerosis (ALS). However, previous research has focused on specific pathogens and rarely examined the influence of infection on disease progression.

To assess whether hospital-treated infections correlate with the risk and prognosis of ALS.

Using data from the Swedish Motor Neuron Disease Quality Registry, we conducted three nested case-control studies, including 1159 individuals diagnosed with ALS during 2015-2023 and 5795 age- and sex-matched population controls, 1558 full-sibling controls, and 680 spouse controls, respectively. We used conditional logistic regression to estimate the association of hospital-treated infections with subsequent risk of ALS and Cox model to assess the association of pre- or post-diagnostic infections with mortality after an ALS diagnosis.

Hospital-treated infections before diagnosis were associated with an increased risk of ALS in the population comparison (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.15-1.49). A similar association was noted after excluding infections within 3-, 5-, or 10-years preceding ALS diagnosis and was confirmed in sibling and spouse comparisons, although results were not always statistically significant. Patients with a hospital-treated infection before diagnosis were more likely to present with bulbar symptoms, poorer functional status, and higher prevalence of anxiety and depressive symptoms at diagnosis than others. Pre-diagnostic infections were not associated with mortality, whereas post-diagnostic infections were associated with increased mortality (hazard ratio [HR] 1.89; 95%CI 1.59-2.24) among ALS patients.

Hospital-treated infections are associated with an increased risk of ALS and may modify its clinical presentation at diagnosis. Post-diagnostic infections are associated with poor survival in ALS.