Cerebrospinal fluid in COVID-19 neurological complications: Neuroaxonal damage, anti-SARS-Cov2 antibodies but no evidence of cytokine storm

  1. Maria A. Garcia
  2. Paula V. Barreras
  3. Allie Lewis
  4. Gabriel Pinilla
  5. Lori J. Sokoll
  6. Thomas Kickler
  7. Heba Mostafa
  8. Mario Caturegli
  9. Abhay Moghekar
  10. Kathryn C. Fitzgerald
  11. Carlos A. Pardo

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Abstract

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  1. Version published to 10.1016/j.jns.2021.117517
  2. ScreenIT

    SciScore for 10.1101/2021.01.10.20249014: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study Approval: This study was approved by the Johns Hopkins Institutional Review Board (IRB) for longitudinal acquisition of clinical and biological samples in patients with neurological disorders.
    Consent: An informed consent was obtained from each patient or next-of-kin representative.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The CSF was examined for 1) the presence of SARS-CoV2 virus, 2) antibody responses against SARS-CoV2, 3) selected cytokines associated with the systemic inflammatory response in COVID-19,(35-38) 4) markers of coagulation and acute phase reactants, and 5) NF-L, a marker of neuroaxonal damage.
    SARS-CoV2, 3
    suggested: None
    NF-L
    suggested: None
    COVID-19 diagnosis was based on a positive NS-NAAT or demonstration of serum anti-SARS-CoV2 IgG or IgA antibodies.
    anti-SARS-CoV2 IgG
    suggested: None
    IgA
    suggested: None
    Software and Algorithms
    SentencesResources
    Complete neurological examination, neuroimaging and laboratory data were recorded in a REDCap database of the Johns Hopkins Division of Neuroimmunology and Neuroinfectious Diseases-CSF Biorepository (NINI-CSFBiorep).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Statistical analysis was performed in Stata v.14. (StataCorp, Texas, USA).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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: We detected the following sentences addressing limitations in the study:
    An important caveat is that we did not test the full spectrum of reported neurologic complications in COVID-19, including multiple cranial neuropathies, ADEM, or GBS, and CSF analysis in those conditions may show different results. We failed to detect SARS-CoV2 viral RNA in the CSF of all COVID-19 subjects examined, concurring with other studies(16, 18-21). The lack of SARS-CoV2 RNA in the CSF may be interpreted as lack of neuro-invasiveness, absence of active viral replication or simply a relatively low viral trafficking into the CNS. Although the detection of RNA viruses in CSF has been historically challenging in some viral disorders of the CNS,(45) the absence of viral RNA along with the lack of pleocytosis and other inflammatory changes in the CSF of COVID-19 patients supports the conclusion that there is not an active trafficking of SARS-CoV2 into the CNS causing neuroinflammation. This distinguishes it from other RNA viruses like poliomyelitis, enterovirus, West-Nile virus that are difficult to detect but produce blatant signs of neuroinflammation in the CSF(45-47). A noteworthy observation in our study is a high prevalence (77%) of SARS-CoV2 spike IgG antibodies in the CSF of COVID-19 cases. Given the absence of viral RNA in the CSF, the lack of pleocytosis which may facilitate B-cells trafficking into the CNS, and absence of intrathecal IgG production (e.g., IgG index, OCBs), CSF antibodies to SARS-CoV2 likely originate from serum and then transfer into the CNS despi...

    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.

  3. Version published to 10.1101/2021.01.10.20249014v1 on medRxiv