Serum neurofilament light chain (sNfL) values in a large cross-sectional population of children with asymptomatic to moderate COVID-19
Authors: Geis Tobias , Brandstetter Susanne , Toncheva Antoaneta A. , Laub Otto , Leipold Georg , Wagner Ralf , Kabesch Michael , Kasser Severin , Kuhle Jens , Wellmann Sven ,   CoKiBa Study group, Aichholzer Bettina , Mair Georg , Wruk Michaela , Reischl Imke , Ambrosch Andreas , Antos David , von Koskull Stephan , Becker Christian , Beer Elisabeth , Schirmer Hubert , Birkinger Georg , Blueml Andreas , Buntrock-Döpke Heike , Castrop Mona , Dieckerhoff Jost , Eichhorn Renate , Ewald Dominik , Heihoff Gudrun Fleck Alfred , Geuder Jürgen , Grombach Jens , Gutdeutsch Peter , Segerer Florian , Habash Thomas , Habash Sonja , Harner Susanne , Herbst Christoph , Heuschmann Daniela , Hofmann Meike , Horn Michael , Jork-Kaeferlein Birgit , Schwarz Monika , Hopfner Reinhard , Judex Guido , Baumgartner Bastian , Corbacioglu Monika , Lindner Sabrina , Meinel Bettina , Bauer Alena , Löw Hannes , Szulagyi-Kovacs Annamaria , Laub Sarah , Klein Annegret , Koering Cosima , Landvogt Niclas , Soehngen Claudia , Rasp Karin , Schick-Niedermeier Gudrun , Laub Marinus , Laub Otto , Leipold Georg , Schmid-Seibold Petra , Pawlak Johannes , Reitz Michaela , Puchner Georg , Peterhoff David , Razeghi Christiane , Razeghi Stefan , Rehe Christine , Rehe Klaus , Scheffel Matthias , Kaesbauer Ludwig , Schmid Roland , Strobelt Michael , Schoetzau Nina , Schweiger-Kabesch Andrea , Senjor Marko , Sperlich Michael , Theuerer Guenter , Steidle Guenter , Tretter German , von Arnim Victor , Volz-Fleckenstein Marlene , Einhauser Sebastian , Neckermann Patrick , Borchers Natascha , Santos-Valente Elisangela , Kheiroddin Parastoo , Schöberl Patricia , Niggel Jakob , Gerling Stephan 
Published: April 2021

Abstract
Background
Serum neurofilament light chain (sNfL) is an established biomarker of neuro-axonal damage in multiple neurological disorders. Raised sNfL levels have been reported in adults infected with pandemic coronavirus disease 2019 (COVID-19). Levels in children infected with COVID-19 have not as yet been reported.

Objective
To evaluate whether sNfL is elevated in children contracting COVID-19.

Methods
Between May 22 and July 22, 2020, a network of outpatient pediatricians in Bavaria, Germany, the Coronavirus antibody screening in children from Bavaria study network (CoKiBa), recruited healthy children into a cross-sectional study from two sources: an ongoing prevention program for 1–14 years, and referrals of 1–17 years consulting a pediatrician for possible infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We determined sNfL levels by single molecule array immunoassay and SARS-CoV-2 antibody status by two independent quantitative methods.

Results
Of the 2652 included children, 148 (5.6%) were SARS-CoV-2 antibody positive with asymptomatic to moderate COVID-19 infection. Neurological symptoms—headache, dizziness, muscle aches, or loss of smell and taste—were present in 47/148 cases (31.8%). Mean sNfL levels were 5.5 pg/ml (SD 2.9) in the total cohort, 5.1 (SD 2.1) pg/ml in the children with SARS-CoV-2 antibodies, and 5.5 (SD 3.0) pg/ml in those without. Multivariate regression analysis revealed age—but neither antibody status, antibody levels, nor clinical severity—as an independent predictor of sNfL. Follow-up of children with pediatric multisystem inflammatory syndrome (n = 14) showed no association with sNfL.

Conclusions
In this population study, children with asymptomatic to moderate COVID-19 showed no neurochemical evidence of neuronal damage.