Brain cortical changes are related to inflammatory biomarkers in hospitalized SARS-CoV-2 patients with neurological symptoms

  1. Gretel Sanabria-Diaz
  2. Manina Maja Etter
  3. Lester Melie-Garcia
  4. Johanna Lieb
  5. Marios-Nikos Psychogios
  6. Gregor Hutter
  7. Cristina Granziera

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Abstract

Increasing evidence shows that the brain is a target of SARS-CoV-2. However, the consequences of the virus on the cortical regions of hospitalized patients are currently unknown. The purpose of this study was to assess brain cortical gray matter volume (GMV), thickness (Th), and surface area (SA) characteristics in SARS-CoV-2 hospitalized patients with a wide range of neurological symptoms and their association with clinical indicators of inflammatory processes. A total of 33 patients were selected from a prospective, multicenter, cross-sectional study during the ongoing pandemic (August 2020-April 2021) at Basel University Hospital. Retrospectively biobank healthy controls with the same image protocol served as controls group. For each anatomical T1w MPRAGE image, the Th and GMV segmentation were performed with the FreeSurfer-5.0. Cortical measures were compared between groups using a linear regression model. The covariates were age, gender, age*gender, MRI magnetic field strength, and total intracranial volume/mean Th/Total SA. The association between cortical features and laboratory variables was assessed using partial correlation adjusting for the same covariates. P-values were adjusted using false discovery rate (FDR). Our findings revealed a lower cortical gray matter volume in orbitofrontal and cingulate regions in patients compared to controls. The orbitofrontal grey matter volume was negatively associated with protein levels, CSF-blood/albumin ratio and CSF EN-RAGE level. CSF EN-RAGE and CSF/Blood-albumin ratio, which are neuroinflammatory biomarkers, were associated with cortical alterations in gray matter volume and thickness in frontal, orbitofrontal, and temporal regions. Our data suggest that viral-triggered inflammation leads to increased neurotoxic damage in some cortical areas.

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    SciScore for 10.1101/2022.02.13.22270662: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants remained anonymous, and written consent was given by the patients or a legal representative.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Cortical thickness (Th) and volumetric segmentation were performed with the FreeSurfer-6.0 image analysis suite (http://surfer.nmr.mgh.harvard.edu/).
    http://surfer.nmr.mgh.harvard.edu/
    suggested: (FreeSurfer, RRID:SCR_001847)
    The statistical analysis was performed using the JASP-software (https://jasp-stats.org/) and MATLAB-software for the partial-correlation analysis (‘partialcorri.m’) (https://www.mathworks.com/).
    https://jasp-stats.org/
    suggested: (JASP, RRID:SCR_015823)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04472013Active, not recruitingSystematic Assessment of SARS-CoV-2 Neurotropic Capacity in …

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2022.02.13.22270662v1 on medRxiv