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

Manina M. Etter, Tomás A. Martins, Laila Kulsvehagen, Elisabeth Pössnecker, Wandrille Duchemin, Sabrina Hogan, Gretel Sanabria-Diaz, Jannis Müller, Alessio Chiappini, Jonathan Rychen, Noëmi Eberhard, Raphael Guzman, Luigi Mariani, Lester Melie-Garcia, Emanuela Keller, Ilijas Jelcic, Hans Pargger, Martin Siegemund, Jens Kuhle, Johanna Oechtering, Caroline Eich, Alexandar Tzankov, Matthias S. Matter, Sarp Uzun, Özgür Yaldizli, Johanna M. Lieb, Marios-Nikos Psychogios, Karoline Leuzinger, Hans H. Hirsch, Cristina Granziera, Anne-Katrin Pröbstel and Gregor Hutter ()
Additional contact information
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
Alessio Chiappini: University Hospital Basel
Jonathan Rychen: University Hospital Basel
Noëmi Eberhard: University Hospital Basel
Raphael Guzman: University Hospital Basel
Luigi Mariani: University Hospital Basel
Lester Melie-Garcia: University of 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
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
Hans H. Hirsch: University Hospital Basel
Cristina Granziera: University of Basel
Anne-Katrin Pröbstel: University of Basel
Gregor Hutter: University of Basel

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34068-0

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