The landscape of human brain immune response in patients with severe COVID-19

  1. John F. Fullard
  2. Hao-Chih Lee
  3. Georgios Voloudakis
  4. Shengbao Suo
  5. Zhiping Shao
  6. Cyril Peter
  7. Behnam Javidfar
  8. Wen Zhang
  9. Shan Jiang
  10. André Corvelo
  11. Emma Woodoff-Leith
  12. Dushyant P. Purohit
  13. Gabriel E. Hoffman
  14. Schahram Akbarian
  15. Mary Fowkes
  16. John Crary
  17. Guo-Cheng Yuan
  18. Panos Roussos

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Abstract

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between brain tropism, neuroinflammation and host immune response has not been well characterized. We analyzed 68,557 single-nucleus transcriptomes from three brain regions (dorsolateral prefrontal cortex, medulla oblongata and choroid plexus) and identified an increased proportion of stromal cells and monocytes in the choroid plexus of COVID-19 patients. Differential gene expression, pseudo-temporal trajectory and gene regulatory network analyses revealed microglial transcriptome perturbations, mediating a range of biological processes, including cellular activation, mobility and phagocytosis. Quantification of viral spike S1 protein and SARS-CoV-2 transcripts did not support the notion of brain tropism. Overall, our findings suggest extensive neuroinflammation in patients with acute COVID-19.

One Sentence Summary

Single-nucleus transcriptome analysis suggests extensive neuroinflammation in human brain tissue of patients with acute coronavirus disease 2019.

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    SciScore for 10.1101/2021.01.08.425999: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    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

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  2. Version published to 10.1101/2021.01.08.425999v1 on bioRxiv