Serum neurofilament light chain in COVID-19 and the influence of renal function

Abstract

COVID-19 is associated with various neurological symptoms. Serum neurofilament light chain (sNfL) is a robust marker for neuroaxonal injury. Recent studies have shown that elevated levels of sNfL are associated with unfavorable outcome in COVID-19 patients. However, neuroaxonal injury is rare in COVID-19, and renal dysfunction and hypoxia, both of which are known in severe COVID-19, can also increase sNfL levels. Thus, the meaning and mechanisms of sNfL elevation in COVID-19 patients remain unclear. We evaluated sNfL levels in 48 patients with COVID-19 (mean age = 63 years) and correlated them to clinical outcome, the form of oxygen therapy, and creatinine. Levels of sNfL were age adjusted and compared with normal values and z-scores. COVID-19 patients treated with nasal cannula had normal sNfL levels (mean sNfL = 19.6 pg/ml) as well as patients with high-flow treatment (mean sNfL = 40.8 pg/ml). Serum NfL levels were statistically significantly higher in COVID-19 patients treated with mechanical ventilation on intensive care unit (ICU) (mean sNfL = 195.7 pg/ml, p < 0.01). There was a strong correlation between sNfL elevation and unfavorable outcome in COVID-19 patients (p < 0.01). However, serum creatinine levels correlated directly and similarly with sNfL elevation and with unfavorable outcome in COVID-19 patients (p < 0.01). Additionally, multivariate analysis for serum creatinine and sNfL showed that both variables are jointly associated with clinical outcomes. Our results identify renal dysfunction as an important possible confounder for sNfL elevation in COVID-19. Thus, serum creatinine and renal dysfunction should be strongly considered in studies evaluating sNfL as a biomarker in COVID-19.

Non‐neurological factors associated with serum neurofilament levels in the United States population

“…Renal function was also reported to be associated with sNfL in a Swiss study of atrial fibrillation (mean age 73.3 years) 11 . In COVID‐19 patients on mechanical ventilation, sNfL was associated with unfavorable outcomes and also with serum creatinine 8 . Our work has systematically extended the sNfL associations to a broader range of blood and urinary renal function markers and a more diverse and representative United States population.…”

“… 11 In COVID‐19 patients on mechanical ventilation, sNfL was associated with unfavorable outcomes and also with serum creatinine. 8 Our work has systematically extended the sNfL associations to a broader range of blood and urinary renal function markers and a more diverse and representative United States population. We were also able to assess Klotho, a proposed aging biomarker candidate that has also been linked to kidney failure.…”

“…sNfL was increased in COVID‐19 patients on mechanical ventilation, and associated with unfavorable outcomes. 8 Increased sNfL has recently been linked to environmental exposures to the herbicide glyphosate and to phthalates, which are additives in plastics. 9 , 10 …”