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

Background 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. Objectives To assess whether hospital‐treated infections correlate with the risk and prognosis of ALS. Methods 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. Results 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. Conclusion 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.