Neurofilament light chain levels predict encephalopathy and outcome in community‐acquired pneumonia

OBJECTIVE: Serum neurofilament light chain (sNfL) is a biomarker for neuroaxonal damage and has been found to be elevated in several neurological diseases with neuronal destruction. New onset of confusion is a hallmark of severity in infections. The objective of this study was to determine whether sNfL levels are increased in patients with community‐acquired pneumonia (CAP) and if increased sNfL levels are associated with disease‐associated confusion or disease severity. METHODS: In this observational study, sNfL levels were determined with single‐molecule array technology in CAP patients of the CAPNETZ cohort with validated CRB (confusion, respiratory rate, and blood pressure)‐65 score. We determined associations between log‐transformed sNfL concentrations, well‐defined clinical characteristics, and unfavorable outcome in multivariable analyses. Receiver operating characteristic (ROC) analysis was performed to assess the prediction accuracy of sNfL levels for confusion in CAP patients. RESULTS: sNfL concentrations were evaluated in 150 CAP patients. Patients with confusion had higher sNfL levels as compared to non‐confusion patients of comparable overall disease severity. ROC analysis of sNfL and confusion provided an area under the curve (AUC) of 0.73 (95% CI 0.62–0.82). Log‐transformed sNfL levels were not associated with general disease severity. In a logistic regression analysis, log2‐sNfL was identified as a strong predictor for an unfavorable outcome. INTERPRETATION: sNfL levels are specifically associated with confusion and not with pneumonia disease severity, thus reflecting a potential objective marker for encephalopathy in these patients. Furthermore, sNfL levels are also associated with unfavorable outcome in these patients and might help clinicians to identify patients at risk.