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.