Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection

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Abstract

SARS-CoV-2 causes acute respiratory disease, but many patients also experience neurological complications. Neuropathological changes with pronounced neuroinflammation have been described in individuals after lethal COVID-19, as well as in the CSF of hospitalized patients with neurological complications. To assess whether neuropathological changes can occur after a SARS-CoV-2 infection, leading to mild-to-moderate disease, we investigated the brains of four rhesus and four cynomolgus macaques after pulmonary disease and without overt clinical symptoms. Postmortem analysis demonstrated the infiltration of T-cells and activated microglia in the parenchyma of all infected animals, even in the absence of viral antigen or RNA. Moreover, intracellular α-synuclein aggregates were found in the brains of both macaque species. The heterogeneity of these manifestations in the brains indicates the virus’ neuropathological potential and should be considered a warning for long-term health risks, following SARS-CoV-2 infection.

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  1. SciScore for 10.1101/2021.02.23.432474: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The research protocol was approved by an independent animal ethics committee (DEC), as well as BPRC’s institutional animal welfare body (IvD).
    Randomizationnot detected.
    BlindingThe counting of cells was performed in a blind matter.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line AuthenticationAuthentication: Hematoxyline-eosine (HE) staining was used for general morphology.

    Table 2: Resources

    Antibodies
    SentencesResources
    Sections were stained with virus antibody staining for virus detection and immunohistochemistry for immune reaction such as T-cell staining (CD3), B-cell staining (CD20), MHC-II cell staining (HLA-DR).
    CD20
    suggested: None
    HLA-DR
    suggested: None
    Immunohistochemistry: The optimal concentration was determined for each antibody: CD3 (polyclonal rabbit – anti-human CD3 IgG, cat. no. A045201-2
    CD3
    suggested: None
    anti-human CD3 IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    All macaques were mature, outbred animals, purpose-bred and socially housed at the BPRC.
    BPRC
    suggested: None
    2, Agilent Technologies), 1:150.
    Agilent Technologies
    suggested: (Agilent Technologies, RRID:SCR_013575)

    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.