Human Taste Cells Express ACE2: a Portal for SARS-CoV-2 Infection

  1. Máire E Doyle
  2. Ashley Appleton
  3. Qing-Rong Liu
  4. Qin Yao
  5. Caio Henrique Mazucanti
  6. Josephine M Egan

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Abstract

Loss and changes in taste and smell are well-reported symptoms of SARS-CoV-2 infection. The virus targets cells for entry by high affinity binding of its spike protein to cell-surface angiotensin-converting enzyme-2 (ACE2). It was not known whether ACE2 is expressed on taste receptor cells (TRCs) nor if TRCs are infected directly. Using an in-situ hybridization (ISH) probe and an antibody specific to ACE2, it seems evident that ACE2 is present on a subpopulation of specialized TRCs, namely, PLCβ 2 positive, Type II cells in taste buds in taste papillae. Fungiform papillae (FP) of a SARS-CoV-2+ patient exhibiting symptoms of COVID-19, including taste changes, were biopsied. Based on ISH, replicating SARS-CoV-2 was present in Type II cells of this patient. Therefore, taste Type II cells provide a portal for viral entry that predicts vulnerabilities to SARS-CoV-2 in the oral cavity. The continuity and cell turnover of the FP taste stem cell layer of the patient were disrupted during infection and had not fully recovered 6 weeks post symptom onset. Another patient suffering post-COVID-19 taste disturbances also had disrupted stem cells. These results indicate that a COVID-19 patient who experienced taste changes had replicating virus in their taste buds and that SARS-CoV-2 infection results in deficient stem cell turnover needed for differentiation into TRCs.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.21.440680: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Fresh human fungiform papillae (FP), ≤ eight per participant, were obtained with IRB approval (IRB/NIH # 2018-AG-N010, -N322) and with participants’ written consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Controls used were incubation without primary antibody, isotype controls, and pre-absorption with a 5-fold excess of the blocking peptide (ACE2).
    ACE2
    suggested: None
    Software and Algorithms
    SentencesResources
    All figures were compiled in Adobe Illustrator 2021 (San Jose, CA) RNAscope in situ hybridization (ISH): RNAscope probes were all from Advanced Cell Diagnostics (Newark, CA; Table 2).
    Adobe Illustrator
    suggested: (Adobe Illustrator, RRID:SCR_010279)
    Images were acquired using Zen software on a Zeiss LSM 880 confocal microscope.
    Zen
    suggested: None
    One-way analysis of variance (ANOVA) with Tukey’s multiple comparison was performed using GraphPad Prism 9 (GraphPad Software Inc.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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 22. 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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2021.04.21.440680v1 on bioRxiv