Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19

Abstract

Brain imaging studies of patients with COVID-19 show evidence of macro- and micro-hemorrhagic lesions, multifocal white matter hyperintensities, and lesions consistent with posterior reversible leukoencephalopathy. Imaging studies, however, are subject to selection bias and prospective studies are challenging to scale. Here, we evaluated whether serum neurofilament light chain (NFL), a neuroaxonal injury marker, could predict the extent of neuronal damage in a cohort of 142 hospitalized patients with COVID-19. NFL was elevated in the serum of patients with COVID-19 compared to healthy controls, including those without overt neurological manifestations. Higher NFL serum concentrations were associated with worse clinical outcomes. In one hundred hospitalized patients with COVID-19 treated with remdesivir, a trend toward lower NFL serum concentrations was observed. These data suggest that patients with COVID-19 may experience neuroaxonal injury and may be at risk for long-term neurological sequelae. Neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.

Neurocognitive Screening in Patients Following SARS-CoV-2 Infection: Tools for Triage

“…For patients with moderatelyto-severely elevated anxiety and depression symptoms, referral for psychiatric evaluation should also be considered. Finally, the detection of focal neurocognitive deficits may warrant further neurological work-up to assess for structural contributors to dysfunction (e.g., neuroimaging to assess for stroke), biofluid markers of inflammation (e.g., cerebrospinal fluid assessment for leukocytosis, or serum measures of neurofilament light [32], or other issues (e.g., polysomnography to assess for occult sleep dysfunction), which may influence long-term prognosis or benefit from specific treatment (Figure 4).…”

Potential role of neurofilament in COVID-19 and preeclampsia

“…sNFL is an easily accessible age-dependent biomarker, commonly used to screen for disease severity and/or progression in several pathologies related to neuronal loss. NFL has also been detected in the CSF of critically ill 4 and the serum of hospitalized individuals 5 with COVID-19. This study demonstrated a positive correlation of sNFL with worse clinical outcomes and COVID-19 severity.…”

Cognitive symptoms after COVID-19

“…Some authors have found that patients with COVID-19 admitted to the ICU show elevated levels of glial fibrillary acidic protein and neurofilament light protein (NfL) in the blood, ( 44 , 45 ) and that high NfL levels are associated with poorer prognosis. ( 44 , 46 , 47 ) A recent study including 142 hospitalised patients found that even patients with no neurological symptoms presented high NfL levels, and that high levels were associated with poor outcomes. ( 47 ) Another study reported elevated plasma levels of IL-4 and markers of neuronal damage in neuronal-enriched extracellular vesicles in patients with neurological symptoms.…”

“…( 44 , 46 , 47 ) A recent study including 142 hospitalised patients found that even patients with no neurological symptoms presented high NfL levels, and that high levels were associated with poor outcomes. ( 47 ) Another study reported elevated plasma levels of IL-4 and markers of neuronal damage in neuronal-enriched extracellular vesicles in patients with neurological symptoms. ( 48 ) However, few studies have analysed biomarkers in patients undergoing cognitive assessment.…”