Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Michael, B. D. et al. (2023) Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses. Nature Communications, 14, 8487. (doi: 10.1038/s41467-023-42320-4) (PMID:38135686) (PMCID:PMC10746705)

[img] Text
315366.pdf - Published Version
Available under License Creative Commons Attribution.



To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.

Item Type:Articles
Additional Information:This research was funded by the National Institute for Health and Care Research (NIHR) (CO-CIN-01) and jointly by NIHR and UK Research and Innovation (CV220-169, MC_PC_19059). B.D.M. is supported by the UKRI/MRC (MR/V03605X/1), the MRC/UKRI (MR/V007181/1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). C.D. is supported by MRC (MC_PC_19044). We would like to thank the University of Liverpool GCP laboratory facility team for Luminex assistance and the Liverpool University Biobank team for all their help, especially Dr. Victoria Shaw, Lara Lavelle-Langham, and Sue Holden. We would like to acknowledge the Liverpool Experimental Cancer Medicine Centre for providing infrastructure support for this research (Grant Reference: C18616/A25153). We acknowledge the Liverpool Centre for Cell Imaging (CCI) for provision of imaging equipment (Dragonfly confocal microscope) and excellent technical assistance (BBSRC grant number BB/R01390X/1). Tom Solomon is supported by The Pandemic Institute and the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool. D.K.M. and E.N. are supported by the NIHR Cambridge Biomedical Centre and by NIHR funding to the NIHR BioResource (RG94028 and RG85445), and by funding from Brain Research UK 201819-20.
Glasgow Author(s) Enlighten ID:Basu, Professor Neil and Cavanagh, Professor Jonathan and Palmarini, Professor Massimo and Thomson, Professor Emma and Patel, Professor Arvind
Authors: Michael, B. D., Dunai, C., Needham, E. J., Tharmaratnam, K., Williams, R., Huang, Y., Boardman, S. A., Clark, J. J., Sharma, P., Subramaniam, K., Wood, G. K., Collie, C., Digby, R., Ren, A., Norton, E., Leibowitz, M., Ebrahimi, S., Fower, A., Fox, H., Tato, E., Ellul, M. A., Sunderland, G., Held, M., Hetherington, C., Egbe, F. N., Palmos, A., Stirrups, K., Grundmann, A., Chiollaz, A.-C., Sanchez, J.-C., Stewart, J. P., Griffiths, M., Solomon, T., Breen, G., Coles, A. J., Kingston, N., Bradley, J. R., Chinnery, P. F., Cavanagh, J., Irani, S. R., Vincent, A., Baillie, J. K., Openshaw, P. J., Semple, M. G., Taams, L. S., Menon, D. K., ISARIC4C Investigators, , , , , , , , , , and COVID-CNS Consortium,
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Nature Communications
Publisher:Nature Research
ISSN (Online):2041-1723
Copyright Holders:Copyright © TheAuthor(s) 2023
First Published:First published in Nature Communications 14:8487
Publisher Policy:Reproduced under a creative commons licence

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
310665ISARIC - Coronavirus Clinical Characterisation ConsortiumAntonia HoMedical Research Council (MRC)MC_PC_19059 - 9815274SII - Virology