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Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Author

Listed:
  • Manina M. Etter

    (University of Basel)

  • Tomás A. Martins

    (University of Basel)

  • Laila Kulsvehagen

    (University of Basel)

  • Elisabeth Pössnecker

    (University of Basel)

  • Wandrille Duchemin

    (University of Basel)

  • Sabrina Hogan

    (University of Basel)

  • Gretel Sanabria-Diaz

    (University of Basel)

  • Jannis Müller

    (University of Basel
    University Hospital Basel)

  • Alessio Chiappini

    (University Hospital Basel)

  • Jonathan Rychen

    (University Hospital Basel)

  • Noëmi Eberhard

    (University Hospital Basel)

  • Raphael Guzman

    (University Hospital Basel
    University Hospital Basel)

  • Luigi Mariani

    (University Hospital Basel
    University Hospital Basel)

  • Lester Melie-Garcia

    (University of Basel
    University Hospital Basel)

  • Emanuela Keller

    (University Hospital Zurich)

  • Ilijas Jelcic

    (University Hospital Zurich)

  • Hans Pargger

    (University Hospital Basel)

  • Martin Siegemund

    (University Hospital Basel)

  • Jens Kuhle

    (University Hospital Basel)

  • Johanna Oechtering

    (University of Basel
    University Hospital Basel)

  • Caroline Eich

    (University of Basel)

  • Alexandar Tzankov

    (University of Basel)

  • Matthias S. Matter

    (University of Basel)

  • Sarp Uzun

    (University of Basel)

  • Özgür Yaldizli

    (University of Basel)

  • Johanna M. Lieb

    (University Hospital Basel)

  • Marios-Nikos Psychogios

    (University Hospital Basel)

  • Karoline Leuzinger

    (University Hospital Basel
    University Hospital Basel)

  • Hans H. Hirsch

    (University Hospital Basel
    University of Basel
    University Hospital Basel)

  • Cristina Granziera

    (University of Basel
    University Hospital Basel)

  • Anne-Katrin Pröbstel

    (University of Basel)

  • Gregor Hutter

    (University of Basel
    University Hospital Basel
    University Hospital Basel)

Abstract

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

Suggested Citation

  • Manina M. Etter & Tomás A. Martins & Laila Kulsvehagen & Elisabeth Pössnecker & Wandrille Duchemin & Sabrina Hogan & Gretel Sanabria-Diaz & Jannis Müller & Alessio Chiappini & Jonathan Rychen & Noëmi , 2022. "Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34068-0
    DOI: 10.1038/s41467-022-34068-0
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    References listed on IDEAS

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    1. F. J. Ryan & A. M. Ahern & R. S. Fitzgerald & E. J. Laserna-Mendieta & E. M. Power & A. G. Clooney & K. W. O’Donoghue & P. J. McMurdie & S. Iwai & A. Crits-Christoph & D. Sheehan & C. Moran & B. Fleme, 2020. "Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    2. 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.
    3. Andrew C. Yang & Fabian Kern & Patricia M. Losada & Maayan R. Agam & Christina A. Maat & Georges P. Schmartz & Tobias Fehlmann & Julian A. Stein & Nicholas Schaum & Davis P. Lee & Kruti Calcuttawala &, 2021. "Dysregulation of brain and choroid plexus cell types in severe COVID-19," Nature, Nature, vol. 595(7868), pages 565-571, July.
    4. Sarah Esther Chang & Allan Feng & Wenzhao Meng & Sokratis A. Apostolidis & Elisabeth Mack & Maja Artandi & Linda Barman & Kate Bennett & Saborni Chakraborty & Iris Chang & Peggie Cheung & Sharon Chint, 2021. "New-onset IgG autoantibodies in hospitalized patients with COVID-19," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. Andrew C. Yang & Fabian Kern & Patricia M. Losada & Maayan R. Agam & Christina A. Maat & Georges P. Schmartz & Tobias Fehlmann & Julian A. Stein & Nicholas Schaum & Davis P. Lee & Kruti Calcuttawala &, 2021. "Publisher Correction: Dysregulation of brain and choroid plexus cell types in severe COVID-19," Nature, Nature, vol. 598(7882), pages 4-4, October.
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