The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

  1. Sreekala Nampoothiri
  2. Florent Sauve
  3. Gaëtan Ternier
  4. Daniela Fernandois
  5. Caio Coelho
  6. Monica Imbernon
  7. Eleonora Deligia
  8. Romain Perbet
  9. Vincent Florent
  10. Marc Baroncini
  11. Florence Pasquier
  12. François Trottein
  13. Claude-Alain Maurage
  14. Virginie Mattot
  15. Paolo Giacobini
  16. S. Rasika
  17. Vincent Prevot

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extra-pulmonary origin. Hypothalamic neural circuits play key roles in sex differences, diabetes, hypertension, obesity and aging, all risk factors for severe COVID-19, besides being connected to olfactory/gustative and brainstem cardiorespiratory centers. Here, human brain gene-expression analyses and immunohistochemistry reveal that the hypothalamus and associated regions express angiotensin-converting enzyme 2 and transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, in correlation with genes or pathways involved in physiological functions or viral pathogenesis. A post-mortem patient brain shows viral invasion and replication in both the olfactory bulb and the hypothalamus, while animal studies indicate that sex hormones and metabolic diseases influence this susceptibility.

Article activity feed

  1. Version published to 10.1101/2020.06.08.139329v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.06.08.139329: (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

    Antibodies
    SentencesResources
    Materials and Methods Figures S1-S10 Tables S1-S5 Movie 1 References (91-99) Gene expression analysis for ACE2, TMPRSS2 and correlated genes in the brain: Collection and processing of human tissues: Immunofluorescence labeling – Animal brains: Antibody table: Fluorescence-activated cell sorting and real-time quantitative PCR: RTqPCR primer table:
    ACE2
    suggested: None

    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

    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 10.1101/2020.06.08.139329v1 on bioRxiv