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

Author

Listed:
  • Benedict D. Michael

    (University of Liverpool
    NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool
    The Walton Centre NHS Foundation Trust)

  • Cordelia Dunai

    (University of Liverpool
    NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool)

  • Edward J. Needham

    (University of Cambridge
    University of Cambridge)

  • Kukatharmini Tharmaratnam

    (University of Liverpool)

  • Robyn Williams

    (University of Oxford
    Mayo Clinic)

  • Yun Huang

    (University of Liverpool)

  • Sarah A. Boardman

    (University of Liverpool)

  • Jordan J. Clark

    (University of Liverpool
    Icahn School of Medicine
    Icahn School of Medicine)

  • Parul Sharma

    (University of Liverpool)

  • Krishanthi Subramaniam

    (University of Liverpool)

  • Greta K. Wood

    (University of Liverpool)

  • Ceryce Collie

    (University of Liverpool)

  • Richard Digby

    (University of Cambridge)

  • Alexander Ren

    (University of Cambridge)

  • Emma Norton

    (University of Cambridge)

  • Maya Leibowitz

    (University of Cambridge)

  • Soraya Ebrahimi

    (University of Cambridge)

  • Andrew Fower

    (University of Oxford)

  • Hannah Fox

    (University of Oxford)

  • Esteban Tato

    (King’s College London
    King’s College London)

  • Mark A. Ellul

    (University of Liverpool
    The Walton Centre NHS Foundation Trust)

  • Geraint Sunderland

    (University of Liverpool)

  • Marie Held

    (University of Liverpool)

  • Claire Hetherington

    (University of Liverpool)

  • Franklyn N. Egbe

    (University of Liverpool)

  • Alish Palmos

    (King’s College London
    King’s College London)

  • Kathy Stirrups

    (Cambridge University Hospitals NHS Foundation
    University of Cambridge)

  • Alexander Grundmann

    (University of Southampton
    University Hospital Southampton NHS Foundation Trust)

  • Anne-Cecile Chiollaz

    (University of Geneva)

  • Jean-Charles Sanchez

    (University of Geneva)

  • James P. Stewart

    (University of Liverpool)

  • Michael Griffiths

    (University of Liverpool)

  • Tom Solomon

    (University of Liverpool
    NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool
    The Walton Centre NHS Foundation Trust
    The Pandemic Institute)

  • Gerome Breen

    (King’s College London
    King’s College London)

  • Alasdair J. Coles

    (University of Cambridge)

  • Nathalie Kingston

    (Cambridge University Hospitals NHS Foundation
    University of Cambridge)

  • John R. Bradley

    (Cambridge University Hospitals NHS Foundation
    University of Cambridge)

  • Patrick F. Chinnery

    (University of Cambridge
    Cambridge University Hospitals NHS Foundation)

  • Jonathan Cavanagh

    (University of Glasgow)

  • Sarosh R. Irani

    (University of Oxford
    Mayo Clinic)

  • Angela Vincent

    (University of Oxford)

  • J. Kenneth Baillie

    (University of Edinburgh
    Royal Infirmary of Edinburgh)

  • Peter J. Openshaw

    (Imperial College London
    Imperial College Healthcare NHS Trust)

  • Malcolm G. Semple

    (University of Liverpool
    NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool
    Alder Hey Children’s Hospital NHS Foundation Trust)

  • Leonie S. Taams

    (King’s College London)

  • David K. Menon

    (University of Cambridge)

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.

Suggested Citation

  • 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 , 2023. "Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42320-4
    DOI: 10.1038/s41467-023-42320-4
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    References listed on IDEAS

    as
    1. Matthieu Perreau & Madeleine Suffiotti & Pedro Marques-Vidal & Aurelie Wiedemann & Yves Levy & Cédric Laouénan & Jade Ghosn & Craig Fenwick & Denis Comte & Thierry Roger & Jean Regina & Peter Vollenwe, 2021. "The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    2. Ibolya Rutkai & Meredith G. Mayer & Linh M. Hellmers & Bo Ning & Zhen Huang & Christopher J. Monjure & Carol Coyne & Rachel Silvestri & Nadia Golden & Krystle Hensley & Kristin Chandler & Gabrielle Le, 2022. "Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
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