Retrospective Analysis of Blood Biomarkers of Neurological Injury in Human Cases of Viral Infection and Bacterial Sepsis.

Abstract

Blood biomarkers of neurological injury could provide a rapid diagnosis of central nervous system injury caused by infections. A Food and Drug Administration (FDA)-approved assay for mild traumatic brain injury (TBI) measures glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), which signal astrocyte and neuronal injury, respectively. Here, we assessed the applicability of this biomarker assay for determining infection-induced brain injury. We measured serum levels of GFAP and UCH-L1 retrospectively in serum samples from 3 study populations: (1) human cases infected with Venezuelan equine encephalitis virus (VEEV) and Madariaga virus (MADV) (n = 73), (2) human sepsis patients who were severely ill or diagnosed with encephalitis (n = 66), and (3) sepsis cases that were subsequently evaluated for cognitive impairment (n = 64). In the virus infection group, we found elevated GFAP for VEEV (P = .014) and MADV (P = .011) infections, which correlated with seizures (P = .006). In the bacterial sepsis group, GFAP was elevated in cases diagnosed with encephalitis (P = .0007) and correlated with headaches (P = .0002). In the bacterial sepsis cases with a later cognitive assessment, elevated GFAP (P = .0057) at study enrollment was associated with cognitive impairment 6 months later with a positive prognostic capacity of 79% (95% confidence interval, 66%-95%; P = .0068). GFAP and UCH-L1 levels measured using an FDA-approved assay for TBI may indicate brain injury resulting from viral or bacterial infections and could predict the development of neurological sequelae.