Neurofilament light increases over time in severe COVID-19 and is associated with delirium
Authors: Smeele Patrick J , Vermunt Lisa , Blok Siebe , Duitman Jan Willem ,   AmsterdamUMC COVID-19 Biobank, van Agtmael Michiel , Algera Anne Geke , Appelman Brent , van Baarle Frank , Bax Diane , Beudel Martijn , Bogaard Harm Jan , Bomers Marije , Bonta Peter , Bos Lieuwe , Botta Michela , de Brabander Justin , de Bree Godelieve , de Bruin Sanne , Buis David TP , Bugiani Marianna , Bulle Esther , Chekrouni Nora , Chouchane Osoul , Cloherty Alex , Dijkstra Mirjam , Dongelmans Dave A , Duijvelaar Erik , Dujardin Romein WG , Elbers Paul , Fleuren Lucas , Geerlings Suzanne , Geijtenbeek Theo , Girbes Armand , Goorhuis Bram , Grobusch Martin P , Hafkamp Florianne , Hagens Laura , Hamann Jorg , Harris Vanessa , Hemke Robert , Hermans Sabine M , Heunks Leo , Hollmann Markus , Horn Janneke , Hovius Joppe W , de Jong Menno D , Koning Rutger , Lim Endry HT , van Mourik Niels , Nellen Jeaninne , Nossent Esther J , Olie Sabine , Paulus Frederique , Peters Edgar , Pina-Fuentes Dan AI , van der Poll Tom , Preckel Bennedikt , Raasveld Jorinde , Reijnders Tom , de Rotte Maurits CFJ , Schippers Job R , Schinkel Michiel , Schultz Marcus J , Schrauwen Femke AP , Schuurman Alex , Schuurmans Jaap , Sigaloff Kim , Slim Marleen A , Smeele Patrick , Smit Marry , Stijnis Cornelis S , Stilma Willemke , Teunissen Charlotte , Thoral Patrick , Tsonas Anissa M , Tuinman Pieter R , van der Valk Marc , Veelo Denise , Volleman Carolien , de Vries Heder , Vught Lonneke A , van Vugt Michéle , Wouters Dorien , Zwinderman A H (Koos) , Brouwer Matthijs C , Wiersinga W Joost , Vlaar Alexander PJ , van de Beek Diederik , Nossent Esther J , van Agtmael Michiel A , Heunks Leo M A , Horn Janneke , Bogaard Harm Jan , Teunissen Charlotte E 
Published: July 2022

AbstractNeurological monitoring in sedated Intensive Care Unit patients is constrained by the lack of reliable blood-based biomarkers. Neurofilament light is a cross-disease biomarker for neuronal damage with potential clinical applicability for monitoring Intensive Care Unit patients. We studied the trajectory of neurofilament light over a month in Intensive Care Unit patients diagnosed with severe COVID-19 and explored its relation to clinical outcomes and pathophysiological predictors. Data were collected over a month in 31 Intensive Care Unit patients (166 plasma samples) diagnosed with severe COVID-19 at Amsterdam University Medical Centre, and in the first week after emergency department admission in 297 patients with COVID-19 (635 plasma samples) admitted to Massachusetts General hospital. We observed that Neurofilament light increased in a non-linear fashion in the first month of Intensive Care Unit admission and increases faster in the first week of Intensive Care Unit admission when compared with mild-moderate COVID-19 cases. We observed that baseline Neurofilament light did not predict mortality when corrected for age and renal function. Peak neurofilament light levels were associated with a longer duration of delirium after extubation in Intensive Care Unit patients. Disease severity, as measured by the sequential organ failure score, was associated to higher neurofilament light values, and tumour necrosis factor alpha levels at baseline were associated with higher levels of neurofilament light at baseline and a faster increase during admission. These data illustrate the dynamics of Neurofilament light in a critical care setting and show associations to delirium, disease severity and markers for inflammation. Our study contributes to determine the clinical utility and interpretation of neurofilament light levels in Intensive Care Unit patients.