High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms

  1. Christiana Franke
  2. Caroline Ferse
  3. Jakob Kreye
  4. S. Momsen Reincke
  5. Elisa Sanchez-Sendin
  6. Andrea Rocco
  7. Mirja Steinbrenner
  8. Stefan Angermair
  9. Sascha Treskatsch
  10. Daniel Zickler
  11. Kai-Uwe Eckardt
  12. Rick Dersch
  13. Jonas Hosp
  14. Heinrich J. Audebert
  15. Matthias Endres
  16. J. Christoph Ploner
  17. Harald Prüß

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Abstract

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  1. ScreenIT

    SciScore for 10.1101/2020.07.01.20143214: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Written informed consent for research and publication was obtained from all patients or their legal representative (ethics committee approval, Berlin: EA2/066/20, Freiburg: 153/20, laboratory analysis: EA
    IRB: Written informed consent for research and publication was obtained from all patients or their legal representative (ethics committee approval, Berlin: EA2/066/20, Freiburg: 153/20, laboratory analysis: EA
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Autoantibodies against intracellular and surface antigens relevant for central nervous system diseases were measured by line blots, ELISA and cell-based assays (Labor Berlin, Germany) and included antibodies against amphiphysin, CV2 (CRMP5), GAD65, Hu, Ri, Yo, Ma2/Ta, Tr (DNER), GAD65, glutamate receptor (AMPAR1/2, NMDA)
    amphiphysin , CV2
    suggested: None
    CRMP5
    suggested: None
    GAD65
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1016/j.bbi.2020.12.022
  3. ScreenIT

    SciScore for 10.1101/2020.07.01.20143214: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementWritten informed consent for research and publication was obtained from all patients or their legal representative ( ethics committee approval , Berlin: EA2/066/20 , Freiburg: 153/20 , laboratory analysis: EA 1/258/18)Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableResults Patient characteristics After a median of 12 days [ 7-17 days ] after onset of respiratory symptoms , 11 patients ( median age 67 [ 54-78 years] , 8 male ) presented with a broad spectrum of neurological symptoms , involving down-beat nystagmus ( n=2) , other oculomotor disturbances ( n=2) , aphasia ( n=1) , hyper- and hypoactive delirium ( n=5) , partial , mainly orofacial myoclonus ( n=6) , generalized stimulus-sensitive myoclonus , which improved by sedation and symptomatic treatment ( n=1) , dystonia of the upper extremities ( n=1) , stroke ( n=1 ) and epileptic seizures ( n=1) .

    Table 2: Resources

    Antibodies
    SentencesResources
    We therefore determined whether anti-neurona or anti-glial autoantibodies are present in eleven consecutive severely ill COVID-19 patients presenting with unexplained neurological symptoms .
    anti-glial
    suggested: None
    Autoantibodies against intracellular and surface antigens relevant fo central nervous system diseases were measured by line blots , ELISA and cell-based assays ( Labor Berlin , Germany ) and included antibodies against amphiphysin , CV2 ( CRMP5) , GAD65 , Hu , Ri , Yo , Ma2/Ta , Tr ( DNER) , GAD65 , glutamate receptor ( AMPAR1/2 , NMDA)
    amphiphysin , CV2
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>CRMP5</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">The neuropil pattern in some patients suggests binding surface receptors or ion channels and thus pathogenicity ( Fig . 1A , D) , similar to the rapidly growing group of antibody-mediated encephalitides11 .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>antibody-mediated encephalitides11</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Likewise , the astrocyte pattern in two patients ( Fig . 1E ) is reminiscent of the relatively common form of GFAP antibody encephalitis12 .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>GFAP</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Tissue destruction may lead to th release of brain-restricted ‘neo-antigens’ such as NMDA receptors , and viral material might provide costimulatory signals to antibody-producing cells13 .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>antibody-producing cells13</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">. d. includes antibodies against amphiphysin , CV2 ( CRMP5) , GAD65 , Hu , Ri , Yo , Ma2/Ta , T NMDA) , DPPX , GABAAR , GABABR , mGluR5 , LGI1 ,</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>GAD65</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>mGluR5</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>LGI1</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Several autoantibodies target intracellular antigens, such as (F) densely clustered intraneuronal epitopes, (G) perinuclear antigens or (H) nucleoli (arrowheads) as part of an anti-nuclear antibody response.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>anti-nuclear</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr></table>

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.01.20143214v1 on medRxiv