Increased serum neurofilament light levels portend worse outcomes in COVID-19

Increased serum neurofilament light levels correlated with poor short-term outcomes in patients with COVID-19, according to findings published in Neurology.

The findings indicated that neuronal injury is frequent and “pronounced” in patients who are critically ill, the researchers reported.

“Neurologic symptoms have been reported in up to 36% of patients with COVID-19,” the researchers wrote. “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 (MS and cerebral small vessel disease) diseases of the [central nervous system].”

Raoul Christian Sutter, MD, a professor and senior physician in intensive care medicine at University Hospital Basel in Switzerland, and colleagues examined whether COVID-19 correlated with neuronal damage, based on quantification of sNfl levels. The study included all patients admitted to the University Hospital Basel ICU with suspected COVID-19 infection between March and May 2020.

The researchers measured sNfL concentrations in samples from critically ill adult patients with (n = 29) and without (n = 10) COVID-19 obtained within 48 hours of ICU admission. They also included serum samples from healthy controls (n = 259; median age, 44.3 years; 31.4% men).

Sutter and colleagues collected information on clinical outcomes, including organ failure, delirium, renal function, complications and more, as well as demographic data.

The researchers 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 coinfections 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 researchers observed sNfL levels that were, on average, 2.6 times higher in patients with COVID-19 compared with patients without COVID-19.

Sutter and colleagues found that patients with COVID-19 had median sNfL levels that were 5.7 times higher than healthy controls (P < .001) 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. The researchers observed higher sNfL levels in patients with unfavorable vs. favorable outcomes (55.9 pg/mL vs. 20 pg/mL; P < .001). The multivariable model showed a 2.2-fold risk for unfavorable outcome for every 10 pg/mL increase in sNfL (OR per 10 pg/mL, 2.19; 95% CI, 1.36-4.65), with identical results after the omission of the patient with the highest sNfL level.

The findings from the present study “are well in line” with data from two other recent studies, one in severe COVID-19 and one in mild to moderate COVID-19, that demonstrated increased NfL levels in patients with COVID-19 compared with healthy controls, according to the study results. While larger studies are necessary to confirm the findings from Sutter and colleagues, the researchers wrote that the “early and pronounced increase” in sNfL levels in critically ill patients indicated that sNfL could be used to evaluate treatment effects and identify patients at greater risk for neuronal damage and unfavorable clinical outcomes.

“Our 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 researchers wrote.