Immune-mediated pathogenesis and development of autoimmunity in neurological manifestations of COVID-19

• Applicants: Dr. Christiana Franke; Professor Dr. Harald Prüß; Professor Dr. Clemens Warnke
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2021 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458681139

Final Report Abstract

We investigated neurological aspects of COVID-19 and post-COVID-19, and implemented neurological post-covid-19 outpatient clinics, recognized by local and national media (https://www.zdf.de/nachrichten/zdf-morgenmagazin/corona-post-covid-langzeitfolgencharite-100.html, https://www.ksta.de/ratgeber/gesundheit/diagnose-neuro-covid-ich-habe-gemerkt-dass-ich-ganz-vergesslich-wurde-38470876?cb=1644833205289&). In particular, severe physical and mental fatigue, as well as cognitive deficits are among the most frequent post-COVID-19 symptoms in our cohorts, currently being further investigated. Our experimental data suggest that neurological post-COVID-19 symptoms are most likely not explained by a persistent infection of the CNS with SARS-COV-2. In contrast, antineuronal autoantibodies might play a major role, which provides a starting point for more in-depth studies in the future. First data on autoimmune profiles of CSF/serum pairs obtained from these patients support an immune-mediated pathogenesis, at least in a fraction of the patients in correlation with pathological cognitive screening assessment. Follow-up analyses will clarify whether the here detected autoimmune reactivity can identify a subgroup of patients which may benefit from immunotherapies. Further studies are needed in particular in well-selected individuals with persistent cognitive impairment, and in patients fulfilling the criteria of autoimmune neurological diseases, diagnosed in close temporal association with COVID-19., or vaccination against COVID-19. This will be a focus of our suggested follow-up project.

Publications

• A Neurological Outpatient Clinic for Patients With Post-COVID-19 Syndrome - A Report on the Clinical Presentations of the First 100 Patients. Front Neurol. 2021;12:738405
  Boesl, Fabian; Audebert, Heinrich; Endres, Matthias; Prüss, Harald & Franke, Christiana
  
• CSF analysis in post-COVID-19 is not suggestive of persistent CNS infection. Ann Neurol. 2021 Vov. 1
  Schweitzer, Finja; Goereci, Yasemin; Franke, Christiana; Silling, Steffi; Bösl, Fabian; Maier, Franziska; Heger, Eva; Deiman, Birgit; Prüss, Harald; Onur, Oezguer A.; Klein, Florian; Fink, Gereon R.; Di Cristanziano, Veronica & Warnke, Clemens
  
• Neuro-COVID-19 is more than anosmia: clinical presentation, neurodiagnostics, therapies, and prognosis. Curr Opin Neurol. 2021; 34(3): 423-431
  Schweitzer, Finja; Kleineberg, Nina N.; Göreci, Yasemin; Onur, Oezguer A.; Franke, Christiana & Warnke, Clemens