Prognostic value of serum/plasma neurofilament light chain for COVID‐19‐associated mortality

Abstract

Objective Given the continued spread of coronavirus 2, the early predictors of coronavirus disease 19 (COVID‐19) associated mortality might improve patients' outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuronal injury, have been observed in severe COVID‐19 patients. We investigated whether NfL provides non‐redundant clinical value to previously identified predictors of COVID‐19 mortality. Methods We measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID‐19 patients. Results In cohort 1, we found significantly elevated NfL levels only in critically ill COVID‐19 patients. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following the two other prognostic markers of COVID‐19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between ALC and LDH abnormalities and subsequent rise of NfL implicate that the multi‐organ failure is the most likely cause of neuronal injury in severe COVID‐19 patients. The addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3. Interpretation A substantial increase in serum/plasma NfL reproducibly enhanced COVID‐19 mortality prediction. Combined with other prognostic markers, such as ALC and LDH that are routinely measured in ICU patients, NfL measurements might be useful to identify the patients at a high risk of COVID‐19‐associated mortality, who might still benefit from escalated care.

Neuro-Axonal Damage and Alteration of Blood–Brain Barrier Integrity in COVID-19 Patients

“…These data are in line with Sutter et al [ 55 ], showing that higher plasma NfL levels are associated with unfavorable short-term outcome in COVID-19 patients. Furthermore, in accordance with Aamodt et al [ 56 ], and Masvekar et al [ 57 ], the evaluation of plasma NfL levels on hospital admission might identify COVID-19 patients with either neurological comorbidities or increased risk of progression to severe COVID-19, thus requiring intensive cares, also focused in preventing further CNS injuries. The identification of a blood biomarker, such as plasma NfL, which is able to assess CNS impairment, could be useful to monitor the severity of the disease and optimize treatment strategies.…”

Anthropometric Measurements and Admission Parameters as Predictors of Acute Respiratory Distress Syndrome in Hospitalized COVID-19 Patients

“…Selecting predictors of worse outcomes and understanding the mechanisms responsible for the clinical deterioration of hospitalized COVID-19 patients has been the focus of scientific research for the past 2 years. More than 30 different parameters can be linked with ARDS development in COVID-19, and several risk assessment scores can be found [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 47 , 48 , 49 ]. However, the selection of predictors, as well as their cutoff and aOR values, significantly varies across the literature.…”

“…In a practical manner, it would be beneficial to single out conditions and clinical characteristics associated with ARDS development in order to construct prediction models and promptly single out patients at risk of clinical deterioration. According to the available literature, many parameters are associated with COVID-19 ARDS, such as older age, male sex, certain comorbidities, smoking, impaired gas exchange, elevated biomarkers of inflammation, and impaired coagulation [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. However, the exact selection of predictors and their impact on ARDS development in hospitalized COVID-19 patients are not uniform across the literature, mostly due to the significant heterogeneity of cohort characteristics and methodological approach.…”

A comparison of machine learning algorithms in predicting COVID-19 prognostics

“…S4 and S6). Clinical findings showed that a lower level of blood lymphocyte count is associated with mortality and deteriorating conditions in COVID-19 patients [ 54 – 56 ]. Similarly, our study provided evidence of the significance of basophils and eosinophils when predicting mortality, which is compatible with the results from other studies [ 25 , 51 , 57 , 58 ].…”