Prolonged and extended impacts of SARS-CoV-2 on the olfactory neurocircuit

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Abstract

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.

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  1. SciScore for 10.1101/2021.11.04.467274: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: All animal studies are reviewed and approved by the Institutional Animal Care and Use Committee at UTMB and are conducted according to the National Institutes of Health guidelines.
    Euthanasia Agents: Immunohistochemistry: Hamsters were euthanized using a high-flow rate of CO2 followed by thoracotomy at each time point to collect samples.
    Sex as a biological variableAnimal experiments: Six-week-old female Syrian golden hamsters were purchased from Charles River.
    RandomizationThree regions were randomly selected, with the regions being at least 100 μm apart, and the averaged values were used.
    BlindingStatistical analysis: To prevent arbitrary analysis, all data were randomly and blindly analyzed by two trained human operators.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Samples were incubated for 12 hr in a solution containing the following primary antibodies: olfactory marker protein (OMP, goat polyclonal, 1:5000 dilution; Wako Chemicals), SARS-CoV-2 Nucleocapsid antibody (rabbit polyclonal, 1:100; Sino Biological), anti-Iba1 (rabbit polyclonal, 1:300; Wako), anti-Iba1 for paraffin section (rabbit polyclonal, 1:300; Wako), anti-Iba1 (goat polyclonal, 1:300; Abcam), anti-NQO1 (rabbit polyclonal, 1:300; Cell Signaling), anti-NQO1 (goat polyclonal, 1:300; Abcam), and anti-GFAP antibody (mouse monoclonal, 1:500; Millipore).
    SARS-CoV-2
    suggested: (Bio X Cell Cat# BE0359, RRID:AB_2894778)
    anti-Iba1
    suggested: None
    anti-NQO1
    suggested: None
    anti-GFAP
    suggested: None
    Primary antibodies were detected by incubation for 1 hr with a solution containing the following secondary antibodies; goat anti-rabbit Fluor 488, goat anti-mouse Fluor 568, donkey anti-goat Alexa Fluor 488, and donkey anti-rabbit Alexa Fluor 568 (1:200; Invitrogen).
    anti-rabbit
    suggested: (Molecular Probes Cat# A-11036, RRID:AB_10563566)
    anti-mouse Fluor 568, donkey anti-goat Alexa Fluor 488, and donkey anti-rabbit Alexa Fluor 568
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 (USA/WA-1/2020) was propagated in Vero E6 cells with DMEM supplemented with 2% FBS.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Subsequently, binary images were overlapped onto the original images and the densities were automatically measured using ImageJ software.
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)
    R (https://www.r-project.org/) and custom-written Python scripts were used for statistical analysis.
    https://www.r-project.org/
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)
    Python
    suggested: (IPython, RRID:SCR_001658)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 31. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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.