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

• Published in: Nature communications Vol. 13; no. 1; pp. 6777 - 21
• Main Authors: Etter, Manina M., Martins, Tomás A., Kulsvehagen, Laila, Pössnecker, Elisabeth, Duchemin, Wandrille, Hogan, Sabrina, Sanabria-Diaz, Gretel, Müller, Jannis, Chiappini, Alessio, Rychen, Jonathan, Eberhard, Noëmi, Guzman, Raphael, Mariani, Luigi, Melie-Garcia, Lester, Keller, Emanuela, Jelcic, Ilijas, Pargger, Hans, Siegemund, Martin, Kuhle, Jens, Oechtering, Johanna, Eich, Caroline, Tzankov, Alexandar, Matter, Matthias S., Uzun, Sarp, Yaldizli, Özgür, Lieb, Johanna M., Psychogios, Marios-Nikos, Leuzinger, Karoline, Hirsch, Hans H., Granziera, Cristina, Pröbstel, Anne-Katrin, Hutter, Gregor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 49/91; 59/57; 631/250/256; 692/308/53/2423; 692/617/375/1367; 82/79; Antigens; Autoantigens; Autoimmunity; Blood-brain barrier; Central nervous system; Cerebrospinal fluid; Chronic infection; Coronaviruses; COVID-19; Cross-sectional studies; Cytokine storm; Cytokines; Humanities and Social Sciences; Immunology; Impairment; Inflammation; Long COVID; Microglia; multidisciplinary; Nervous system; Neurodegeneration; Neuroimaging; Neurological complications; Patients; Peripheral blood; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34068-0

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. Both acute and chronic COVID-19 disease (also known as long-COVID) may affect the central nervous system. Here authors characterize the immunological profile of peripheral blood and cerebrospinal fluid of COVID-19 patients in order to identify the main factors that contribute to neurological impairment and the severity of neurological symptoms in Sars-CoV-2 infection.