Neutrophils initiate the destruction of the olfactory epithelium during SARS-CoV-2 infection in hamsters

  1. Bourgon Clara
  2. St Albin Audrey
  3. Ando-Grard Ophélie
  4. Da Costa Bruno
  5. Domain Roxane
  6. Korkmaz Brice
  7. Klonjkowski Bernard
  8. Le Poder Sophie
  9. Meunier Nicolas

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Abstract

The loss of smell related to SARS-CoV-2 infection is one of the most prevalent symptoms of COVID-19. It is now clear that this symptom is related to the massive infection by SARS-CoV-2 of the olfactory epithelium leading to its desquamation. However, the molecular mechanism behind the destabilization of the olfactory epithelium is less clear. Using golden Syrian hamster, we show here that while apoptosis remains at a low level in damaged infected epithelium, the latter is invaded by innate immunity cells. By depleting the neutrophil population or blocking the activity of neutrophil elastase-like proteinases, we reduced the damage induced by the SARS-CoV-2 infection. Surprisingly, the impairment of neutrophil activity led to a decrease of SARS-CoV-2 infection levels in the nasal cavity. Our results indicate a counterproductive role of neutrophils leading to the release of infected cells in the lumen of the nasal cavity and thereby enhanced spreading of the virus.

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  1. ScreenIT

    SciScore for 10.1101/2022.03.15.484439: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Animal experiments were carried out in the animal biosafety level 3 facility of the UMR Virologie (ENVA, Maisons-Alfort); approved by the ANSES/EnvA/UPEC Ethics Committee (CE2A16) and authorized by the French ministry of Research under the number APAFIS#25384-2020041515287655.
    IRB: Animal experiments were carried out in the animal biosafety level 3 facility of the UMR Virologie (ENVA, Maisons-Alfort); approved by the ANSES/EnvA/UPEC Ethics Committee (CE2A16) and authorized by the French ministry of Research under the number APAFIS#25384-2020041515287655.
    Sex as a biological variableAnimals: Fifty-six 8 weeks-old male hamsters were purchased from Janvier’s breeding Center (Le Genest, St Isle, France).
    RandomizationAnimals were randomized to the experimental groups.
    BlindingAll analyses were performed blindly of the treatment.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The sections were then incubated overnight with primary antibodies directed against SARS Nucleocapsid protein (1/500; mouse monoclonal; clone 1C7C7;
    SARS Nucleocapsid protein
    suggested: (LSBio (LifeSpan Cat# LS-C59557-500, RRID:AB_1510641)
    Experimental Models: Cell Lines
    SentencesResources
    Measure of antiviral activity of cyclophosphamide and cathepsin C inhibitor against SARS-CoV-2 in cell culture: Vero E6 cells (CRL-1586, ATCC maintained at 37 °C; 5% CO2) were seeded at 2.104 cells per well in a 96-well plate in Dulbecco’s Modified Eagle’s Medium, 5% foetal bovine serum (FBS-12A, Capricorn Scientific, Clinisciences).
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    All quantifications were made with ImageJ (Rasband, W.S., ImageJ, U.S. National Institutes of Health, Bethesda, Maryland, USA, http://imagej.nih.gov/ii/, 1997–2012) to threshold specific staining.
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)
    iTaq Universal Sybr Green SuperMix (BioRad; #1725124), and primers at 500 nM (sequences in Supp.
    BioRad
    suggested: None
    Statistical analysis: All comparisons were made using Prism 5.0 (GraphPad).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    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: 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.

    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.

  2. Version published to 10.1101/2022.03.15.484439v1 on bioRxiv