Kliniken &… Kliniken Neurologische… Neurologie und… Forschung Neuroimmunology Molecular… COVID-19/SARS-CoV-2 and…

Neuro-COVID-19 and Neuro-Post/Long-COVID | Neuro-COVID-19 und Neuro-Post/Long-COVID

Principal investigators | Projektleiter: Sven Jarius*, Brigitte Wildemann*

The main objects of this reseach project are to clarify the pathogenesis of neurological symptoms in patients with acute COVID-19 and - within the framework of a project funded by the Baden-Württemberg Ministry of Science, Research and the Arts under the auspices of the German Society for CSF Diagnostics and Clinical Neurochemistry - to identify diagnostically, pathogenetically (and thus prospectively therapeutically) and prognostically relevant disease markers in patients with neurological, neuropsychological or psychiatric long-term sequelae of COVID-19 (NP-Post/Long-COVID). A major focus is on the investigation of possible autoimmunological pathomechanisms. Furthermore, the project aims to establish a Post/Long-COVID biobank with a special focus on the collection of cerebrospinal fluid (CSF) samples.

Independent projects are dedicated to investigating the pathophysiological and diagnostic relevance of autoantibodies in other inflammatory diseases of the central and peripheral nervous system (e.g., multiple sclerosis [MS], neuromyelitis optica spectrum disorders [NMOSD]myelin oligodendrocyte glycoprotein autoantibody-associated disorder (MOGAD; also termed MOG encephalomyelitis [MOG-EM]), paraneoplastic and non-paraneoplastic autoimmune encephalitis [including autoimmune cerebellar ataxia], limbic encephalitis, peripheral neuropathy, Susac syndrome, Balo's concentric sclerosis).

Gegenstand unserer Forschung sind ­die Klärung der Pathogenese neurologischer Symptome bei Patienten mit akutem COVID-19 sowie - im Rahmen eines durch das Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg geforderten Projektes unter Schirmherrschaft der Deutschen Gesellschaft für Liquordiagnostik und klinische Neurochemie - die Identifizierung diagnostisch, pathogenetisch (und somit perspektivisch therapeutisch) und prognostisch relevanter Krankheitsmarker bei Patienten mit neurologischen, neuropsychologischen oder psychiatrischen Langzeitfolgen von COVID-19 (NP-Post/Long-COVID). Ein wesentlicher Fokus liegt dabei auf der Untersuchung möglicher autoimmunologischer Pathomechanismen. Ferner ist Ziel des Projektes der Aufbau einer Post-/Long-COVID-Biobank mit Schwerpunkt auf der Sammlung von Hirn- und Rückenmarkswasser (Liquor cerebrospinalis).

Eigenständige Projektbereiche sind der pathophysiologischen und diagnostischen Relevanz von Autoantikörpern bei entzündlichen Erkrankungen des zentralen und/oder peripheren Nervensystems gewidmet (u.a. Multiple Sklerose [MS], Neuromyelitis-optica-Spectrum-Erkrankungen [NMOSD]Myelin-Oligodendrozyten-Glykoprotein-Autoantikörper-assoziierte Enzephalomyelitis (MOG-EM; MOG-Antikörper-assoziierte Erkrankung [MOGAD]), paraneoplastische und nich-paraneoplastische Autoimmunenzephalitiden [inkl. autoimmune zerebelläre Ataxie], limbische Enzephalitis, periphere Neuropathien, Susac-Syndrom, Balo's konzentrische Sklerose).

* Brigitte Wildemann (h-index 68 / 18300 citations [according to Publish or Perish 7.33; data last retrieved 2023-06-20]) is Professor of Neurology and Head of the Molecular Neuroimmunology Group in the Department of Neurology, University of Heidelberg, Germany. Her research goals focus on the immunopathogenesis of multiple sclerosis (MS). Other research interests are neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease/encephalomyelitis (MOGAD/MOG-EM), acute disseminated encephalomyelitis (ADEM), autoimmune encephalitis, and the pathogenetic mechanisms involved in the neuromanifestations of systemic diseases, such as rheumatological disorders and HIV/AIDS. She has authored/co-authored more than 250 peer-reviewed articles and numerous book chapters, has published as lead editor the Thieme standard textbook "Laboratory Diagnosis in Neurology", and is co-author of the German guidelines on MS, NMOSD, MOGAD/MOG-EM, of the German guidelines on CSF analysis, and of the National Recommendation for the use of autologous hematopoietic stem cell transplantation (aHSCT) in MS is in Germany. Brigitte Wildemann is also current president of the German Society for CSF Analysis and Clinical Neurochemistry (DGLN).

Sven Jarius (h-index 73 / 23237 citations [according to Publish or Perish 7.33; data last retrieved 2023-09-26]) is a senior scientist in the field of clinical and basic neuroimmunology who has trained at the Institute of Clinical Neuroimmunology and the Department of Neurology, Ludwig Maximilian University, Munich, Germany, in the Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried/Munich, Germany, and in the Neurosciences Group at the Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, UK. His main topics of interest are neuromyelitis optica spectrum disorders (NMOSD); myelin oligodendrocyte glycoprotein antibody-associated disease/encephalomyelitis (MOGAD/MOG-EM); multiple sclerosis; autoimmune encephalitis, myelitis, and optic neuritis; autoimmune cerebellar ataxia; paraneoplastic neurological syndromes; and the history of neuroscience. Since 2008 he has worked at the Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Germany.  He is lead author or co-author, respectively, of several international diagnostic consensus criteria (NMOSD, MOGAD/MOG-EM, Susac syndrome, primary autoimmune cerebellar ataxia) and first described/was involved in the first description and/or clincal definition of several novel autoimmune disorders. He has published around 240 peer-reviewed articles, including in Nat Rev Dis Primers (IF 65), Nat Rev Neurol (IF 45), Nat Rev Clin Pract, Lancet Neurology, BMJ, Brain, Neurology, Ann Neurol, Arch Neurol, J Neurol, J Neurol Neurosurg Psychiatry, Eur J Neurol, Front Neurol, Curr Opin Neurol, Neurology:Neuroimmunol Neuroinflamm, Acta Neuropathol, Brain Pathol, J Neuroinflammation, J Neuroimmunology, J Immununology, Front Immunol, Adv Immunol, J Autoimmunity, MSJ, MSARD, Arthritis & Rheumatism, and Blood.

Selected publications on COVID-19 and Long-COVID / Ausgewählte Publikationen zum Thema

  • Boesl F, Goereci Y, Gerhard A, Bremer B, Raeder V, Schweitzer F, Hoppmann U, Behrens J, Bellmann-Strobl J, Paul F, Wildemann B, Jarius S, Prüss H, Audebert HJ, Warnke C, Franke C. Cerebrospinal fluid findings in patients with neurological manifestations in post-COVID-19 syndrome. J Neurol. 2023 Nov 24. doi: 10.1007/s00415-023-12092-4. Online ahead of print.
  • Jarius S, Pache F, Kortvelyessy P, Jelcic I, Stettner M, Franciotta D, Keller E, Neumann B, Ringelstein M, Senel M, Regeniter A, Kalantzis R, Willms JF, Berthele A, Busch M, Capobianco M, Eisele A, Reichen I, Dersch R, Rauer S, Sandner K, Ayzenberg I, Gross CC, Hegen H, Khalil M, Kleiter I, Lenhard T, Haas J, Aktas O, Angstwurm K, Kleinschnitz C, Lewerenz J, Tumani H, Paul F, Stangel M, Ruprecht K, Wildemann B, in cooperation with the German Society for Cerebrospinal Fluid Diagnostics and Clinical Neurchemistry. Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients. J Neuroinflammation 2022, 19:19. ENA COVID PAPER OF THE MONTH [FREE PDF]
  • Jarius S, Bieber N, Haas J, Wildemann B. MOG encephalomyelitis after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2): case report and comprehensive review of the literature. J Neurol 2022, 269:5198-5212. [FREE PDF]
  • Wildemann B, Jarius S, Lehmann LH, Andre F, Frey N, Schnitzler P, Jager L, Gumbinger C, Viehover A. COVID-19-related severe MS exacerbation with life-threatening Takotsubo cardiomyopathy in a previously stable patient and interference of MS therapy with long-term immunity against SARS-CoV-2. J Neurol 2022, 269:1138-1141. [FREE PDF]
  • Hummert MW, Butow F, Tkachenko D, Ayzenberg I, Pakeerathan T, Hellwig K, Klotz L, Haussler V, Stellmann JP, Warnke C, Goereci Y, Etgen T, Luessi F, Bronzlik P, Gingele S, Lauenstein AS, Kleiter I, Rommer PS, Paul F, Bellmann-Strobl J, Duchow A, Then Bergh F, Pul R, Walter A, Pellkofer H, Kumpfel T, Pompsch M, Kraemer M, Albrecht P, Aktas O, Ringelstein M, Senel M, Giglhuber K, Berthele A, Jarius S, Wildemann B, Trebst C, Neuromyelitis Optica Study G: Effects of the COVID-19 pandemic on patients with NMO Spectrum Disorders and MOG antibody-associated diseases: COPANMO(G)-Study. Neurol Neuroimmunol Neuroinflamm 2023, 10.
  • Doubrovinskaia S, Mooshage CM, Seliger C, Lorenz HM, Nagel S, Lehnert P, Purrucker J, Wildemann B, Bendszus M, Wick W, Schonenberger S, Kaulen LD. Neurological autoimmune diseases following vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A follow-up study. Eur J Neurol 2023, 30:463-473.
  • Kaulen LD, Doubrovinskaia S, Mooshage C, Jordan B, Purrucker J, Haubner C, Seliger C, Lorenz HM, Nagel S, Wildemann B, Bendszus M, Wick W, Schonenberger S. Neurological autoimmune diseases following vaccinations against SARS-CoV-2: a case series. Eur J Neurol 2022, 29:555-563.
  • Reinhold D, Farztdinov V, Yan Y, Meisel C, Sadlowski H, Kuhn J, Perschel FH, Endres M, Duzel E, Vielhaber S, Guttek K, Goihl A, Veno M, Teegen B, Stocker W, Stubbemann P, Kurth F, Sander LE, Ralser M, Otto C, Streit S, Jarius S, Ruprecht K, Radbruch H, Kjems J, Mulleder M, Heppner F, Kortvelyessy P. The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation. J Neuroinflammation 2023, 20:30.
  • Schwake C, Pakeerathan T, Kleiter I, Ringelstein M, Aktas O, Korporal-Kuhnke M, Wildemann B, Jarius S, Bayas A, Pul R, Ceylan U, Faissner S, Hellwig K, Ayroza Galvao Ribeiro Gomes AB, Lipps P, Probstel AK, Kumpfel T, Oswald E, Then Bergh F, Godel C, Hummert MW, Trebst C, Gold R, Ayzenberg I. Humoral COVID-19 vaccine response in patients with NMOSD/MOGAD during anti-IL-6 receptor therapy compared to other immunotherapies. Mult Scler 2023, 29:757-761.