Increased Serum Neurofilament Light Portend Worse Prognosis in COVID-19

There is emerging evidence for multifarious neurological manifestations of COVID‐19, while little is known whether they reflect structural damage to the nervous system. The most commonly reported neurological manifestations of COVID-19 were myalgia, headache, altered sensorium, hyposmia, and hypogeusia.

Neurofilament light chain (NfL) represents a main constituent of the neuronal cytoskeleton and plays a role in axonal growth, stability and intracellular transport. Serum NfL (sNfL) is a blood-based marker specifically reflecting neuroaxonal damage as shown in studies including acute (ischemic stroke, hypoxic-ischemic encephalopathy) and chronic diseases of the central nervous system.


Neuroscientists at the University Hospital Basel (Basel Switzerland) and their colleagues examined whether COVID-19 correlated with neuronal damage, based on quantification of sNfl levels. The study included all patients admitted to the Hospital’s intensive-care unit (ICU) with suspected COVID-19 infection between March and May 2020. The team measured sNfL concentrations in samples from 29 critically ill adult patients with and 10 without COVID-19 obtained within 48 hours of ICU admission. They also included serum samples from 259 healthy controls (median age, 44.3 years; 31.4% men).

The team observed lower median oxygenation and lymphocyte cell counts during the ICU stay among patients with COVID-19, who also developed delirium more frequently than patients who did not have COVID-19. Patients with COVID-19 experienced longer ICU stays and developed co-infections and thrombotic events more often. Study results demonstrated that previous neurologic comorbidities were more common in patients without COVID-19 (40%) than patients with COVID-19 (10.3%). In the unadjusted analysis, median sNfL levels did not change significantly between patients with and without COVID-19. However, in the multivariable analysis, the scientists observed sNfL levels that were, on average, 2.6 times higher in patients with COVID-19 compared with patients without COVID-19.

The investigators found that patients with COVID-19 had median sNfL levels that were 5.7 times higher than healthy controls and that 69% of these patients had sNfL concentrations above the 99th percentile of healthy controls compared with only 40% of patients without COVID-19. Increased sNfL levels correlated with longer ICU and hospital stays and extended mechanical ventilation, according to the study results. However, after excluding the patient with the highest sNfL level (1,311.7 pg/mL), these relationships lost significance. They observed higher sNfL levels in patients with unfavorable versus favorable outcomes (55.9 pg/mL versus 20 pg/mL). The multivariable model showed a 2.2-fold risk for unfavorable outcome for every 10 pg/mL increase in sNfL with identical results after the omission of the patient with the highest sNfL level.

The authors concluded that their findings underline the overall importance of protecting the nervous system from damage in severely ill patients and suggest sNfL as an early marker to identify patients susceptible to neurological complications and unfavorable outcome. The study was published on December 30, 2020 in the journal Annals of Neurology.

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