Nature Communications (Dec 2023)
Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
- Benedict D. Michael,
- Cordelia Dunai,
- Edward J. Needham,
- Kukatharmini Tharmaratnam,
- Robyn Williams,
- Yun Huang,
- Sarah A. Boardman,
- Jordan J. Clark,
- Parul Sharma,
- Krishanthi Subramaniam,
- Greta K. Wood,
- Ceryce Collie,
- Richard Digby,
- Alexander Ren,
- Emma Norton,
- Maya Leibowitz,
- Soraya Ebrahimi,
- Andrew Fower,
- Hannah Fox,
- Esteban Tato,
- Mark A. Ellul,
- Geraint Sunderland,
- Marie Held,
- Claire Hetherington,
- Franklyn N. Egbe,
- Alish Palmos,
- Kathy Stirrups,
- Alexander Grundmann,
- Anne-Cecile Chiollaz,
- Jean-Charles Sanchez,
- James P. Stewart,
- Michael Griffiths,
- Tom Solomon,
- Gerome Breen,
- Alasdair J. Coles,
- Nathalie Kingston,
- John R. Bradley,
- Patrick F. Chinnery,
- Jonathan Cavanagh,
- Sarosh R. Irani,
- Angela Vincent,
- J. Kenneth Baillie,
- Peter J. Openshaw,
- Malcolm G. Semple,
- ISARIC4C Investigators,
- COVID-CNS Consortium,
- Leonie S. Taams,
- David K. Menon
Affiliations
- Benedict D. Michael
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Cordelia Dunai
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Edward J. Needham
- Department of Clinical Neurosciences, University of Cambridge
- Kukatharmini Tharmaratnam
- Health Data Science, Institute of Population Health, University of Liverpool
- Robyn Williams
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford
- Yun Huang
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Sarah A. Boardman
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Jordan J. Clark
- University of Liverpool
- Parul Sharma
- Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Krishanthi Subramaniam
- Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Greta K. Wood
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Ceryce Collie
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Richard Digby
- Division of Anaesthesia, Department of Medicine, University of Cambridge
- Alexander Ren
- Division of Anaesthesia, Department of Medicine, University of Cambridge
- Emma Norton
- Division of Anaesthesia, Department of Medicine, University of Cambridge
- Maya Leibowitz
- Division of Anaesthesia, Department of Medicine, University of Cambridge
- Soraya Ebrahimi
- Division of Anaesthesia, Department of Medicine, University of Cambridge
- Andrew Fower
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford
- Hannah Fox
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford
- Esteban Tato
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
- Mark A. Ellul
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Geraint Sunderland
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Marie Held
- Centre for Cell Imaging, Liverpool Shared Research Facilities, Faculty of Health and Life Sciences, University of Liverpool
- Claire Hetherington
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Franklyn N. Egbe
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Alish Palmos
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
- Kathy Stirrups
- NIHR BioResource, Cambridge University Hospitals NHS Foundation
- Alexander Grundmann
- Clinical Neurosciences, Clinical and Experimental Science, Faculty of Medicine, University of Southampton
- Anne-Cecile Chiollaz
- Département de médecine interne des spécialités (DEMED), University of Geneva
- Jean-Charles Sanchez
- Département de médecine interne des spécialités (DEMED), University of Geneva
- James P. Stewart
- Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Michael Griffiths
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Tom Solomon
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Gerome Breen
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
- Alasdair J. Coles
- Department of Clinical Neurosciences, University of Cambridge
- Nathalie Kingston
- NIHR BioResource, Cambridge University Hospitals NHS Foundation
- John R. Bradley
- NIHR BioResource, Cambridge University Hospitals NHS Foundation
- Patrick F. Chinnery
- Department of Clinical Neurosciences, University of Cambridge
- Jonathan Cavanagh
- Centre for Immunology, School of Infection & Immunity, College of Medical, Veterinary & Life Sciences, University of Glasgow
- Sarosh R. Irani
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford
- Angela Vincent
- Nuffield Department of Clinical Neurosciences, University of Oxford
- J. Kenneth Baillie
- Roslin Institute, University of Edinburgh
- Peter J. Openshaw
- National Heart and Lung Institute, Imperial College London
- Malcolm G. Semple
- Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- ISARIC4C Investigators
- COVID-CNS Consortium
- Leonie S. Taams
- Centre for Inflammation Biology and Cancer Immunology, King’s College London
- David K. Menon
- Division of Anaesthesia, Department of Medicine, University of Cambridge
- DOI
- https://doi.org/10.1038/s41467-023-42320-4
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 15
Abstract
Abstract 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.
