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 A. Hogan, Gretel Sanabria-Díaz, Jannis Müller, Alessio Chiappini, Jonathan Rychen, Noëmi Eberhard, Raphaël Guzman, Luigi Mariani, Lester Melie‐García, E. Keller, Ilijas Jelčić, Hans Pargger, Martin Siegemund, Jens Kühle, 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, Gregor Hütter
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.