Clinical Validation of Serum Neurofilament Light as a Biomarker of Traumatic Axonal Injury

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ABSTRACT In those who require hospitalization due to infection with the novel coronavirus SARS-CoV-2, a syndrome termed COVID-19, 20% develop critical illness requiring ICU admission.1 COVID-19 critical illness is characterized by multiorgan failure, including acute severe hypoxemic respiratory failure, renal dysfunction, and hemodynamic compromise. Early studies indicate that >30% of hospitalized patients have neurological complications. Critical illness itself is associated with prolonged neurological and psychological impairments that extend far beyond the initial insult, even without obvious brain injury during the acute hospitalization. These disabilities include memory and cognitive dysfunction, depression, and post-traumatic stress disorder. These symptoms are prevalent in survivors of ICU admissions and can be persistent, with at least one or more symptom present in 20-50% of survivors a year or more after hospital discharge. There is reason to be concerned that patients who survive COVID-19 may be at even higher risk, given the prolonged hospital course that is common and the isolation required to contain the contagion. In this study, we aim to analyze neurofilment light (NfL), a biomarker of acute brain injury in patients who are critically ill with COVID-19. We will correlate the expression of NfL with data on neurological compromise in the acute hospitalization as well as long-term cognitive and psychological outcomes. The ultimate goal of this work is to determine if NfL can be used early in the hospital stay to identify patients at highest risk of long-term neurological and psychological compromise. This will help guide management as patients transition from the critical care setting to rehabilitation and recovery.