A proportion of patients with COVID-19 develop neurological symptoms, including headaches, encephalopathy and seizures, but it is unknown to which extent. Most of these patients have no imaging signs of intracranial abnormalities, which may in any case be inadequate to examine neuronal injury in these patients. At the Mayo Clinic, previous work showed that serum neurofilament light chain (NFL) concentrations were associated with radiographic markers of brain tissue damage and indicators of neurological, functional and cognitive status in stroke patients.
This and other studies indicating that NFL is a marker of axonal injury led to investigation of NFL in the context of COVID-19. NFL concentrations were found to be significantly higher in 142 patients with COVID-19 (median 29.4 pg/mL) compared with concentrations in 55 healthy controls (median 10.9 pg/mL). The association withstood correction for age and sex. NFL concentrations at least 3 SDs above the group mean NFL concentration of control individuals (calculated using maximum NFL measurements due to NFL fluctuations) were measured in 34% of the COVID-19 patients. An NFL concentration of at least 2 SDs above the mean control concentration was identified in 53% of patients.
In analyses adjusted for age, sex, body mass index and chronic kidney disease, serum NFL concentrations were significantly higher in patients who needed mechanical ventilation, who were admitted to the ICU, who had a longer length of hospital stay and who had a higher modified Rankin scale (mRS) at discharge. NFL was positively correlated with time from admission to final blood draw.
Longitudinal NFL data from 100 patients with up to 17 serum NFL measurements showed that temporal changes in NFL differed among patients. An exploratory multivariate analysis by treatments given showed lower serum NFL in patients who received remdesivir considering final NFL concentration per patient (P = 0.008).
The study authors concluded that many hospitalized patients with COVID-19 suffer neuronal injury, and that longitudinal measurements of serum NFL could allow for the identification and quantification of this injury. Clinical trials of acute therapies for COVID-19 could also include neuroaxonal injury as an outcome.