Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

DOI: http://doi.org/10.1093/brain/awac321 Journal: Brain E-pub date: 6 Sep 2022 Authors: EJ Needham, AL Ren, RJ Digby, EJ Norton, S Ebrahimi, JG Outtrim, DA Chatfield, AE Manktelow, MM Leibowitz, VFJ Newcombe, R Doffinger, G Barcenas-Morales, C Fonseca, MJ Taussig, RM Burnstein, RJ Samanta, C Dunai, N Sithole, NJ Ashton, H Zetterberg, M Gisslén, A Edén, E Marklund, PJM Openshaw, J Dunning, MJ Griffiths, J Cavanagh, G Breen, SR Irani, A Elmer, N Kingston, C Summers, JR Bradley, LS Taams, BD Michael, ET Bullmore, KGC Smith, PA Lyons, AJ Coles, DK Menon, Cambridge NeuroCOVID Group, CITIID-NIHR COVID-19 BioResource Collaboration, Cambridge NIHR Clinical Research Facility

Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

Abstract:

COVID-19 has been associated with many neurological complications including stroke, delirium and encephalitis. Furthermore, many individuals experience a protracted post-viral syndrome which is dominated by neuropsychiatric symptoms, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of severe COVID-19 more broadly. We sought to investigate the dynamics of, and relationship between, serum markers of brain injury (neurofilament light [NfL], Glial Fibrillary Acidic Protein [GFAP] and total Tau) and markers of dysregulated host response including measures of autoinflammation (proinflammatory cytokines) and autoimmunity. Brain injury biomarkers were measured using the Quanterix Simoa HDx platform, cytokine profiling by Luminex (R&D) and autoantibodies by a custom protein microarray. During hospitalisation, patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependant manner, and there was evidence of ongoing active brain injury at follow-up 4 months later. Raised NfL and GFAP were associated with both elevations of pro-inflammatory cytokines and the presence of autoantibodies; autoantibodies were commonly seen against lung surfactant proteins as well as brain proteins such as myelin associated glycoprotein, but reactivity was seen to a large number of different antigens. Furthermore, a distinct process characterised by elevation of serum total Tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses in the same manner as NfL and GFAP.