Chronic alcohol intake regulates expression of SARS‐CoV2 infection‐relevant genes in an organ‐specific manner

  1. Marion M. Friske
  2. Francesco Giannone
  3. Mona Senger
  4. Robin Seitz
  5. Anita C. Hansson
  6. Rainer Spanagel

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Abstract

Background

Chronic alcohol consumption and alcohol use disorder have a tremendous impact on the patient's psychological and physiological health. There is evidence that chronic alcohol consumption influences SARS‐CoV2 infection risk, but so far, the molecular mechanism underlying such an effect is unknown.

Methods

We generated the expression data of SARS‐CoV2 infection‐relevant genes (Ace2, Tmprss2, and Mas) in different organs in rat models of chronic alcohol exposure and alcohol dependence. Ace2 and Tmprss2 represent the virus entry point, whereas Mas activates the anti‐inflammatory response once the cells are infected.

Results

Across three different chronic alcohol test conditions, we found a consistent upregulation of Ace2 gene expression in the lung, which has been shown to be the most affected organ in COVID‐19 patients. Other organs such as liver, ileum, kidney, heart, and brain also showed upregulation of Ace2 and Mas gene expression but less consistently across the different animal models, while Tmprss2 expression was unaffected in all conditions.

Conclusions

We conclude that alcohol‐induced upregulation of Ace2 gene expression can lead to an elevated stochastic probability of virus entry into cells and may thus confer a molecular risk for SARS‐CoV2 infection.

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  1. Version published to 10.1111/acer.14981
  2. ScreenIT

    SciScore for 10.1101/2022.02.01.478685: (What is this?)

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

    Table 1: Rigor

    EthicsEuthanasia Agents: The animals were sacrificed 6 h after the last IP injection via decapitation, during the active cycle (ZT22), since previous studies have shown that the circadian regulation of Ace2 peaks at this time point (Herichová et al., 2013; Zlacká et al., 2021).
    Sex as a biological variableSub-chronic ethanol IP treatment: Seven weeks old male Wistar rats (Envigo, Ettlingen, Germany) were randomly distributed in groups and cages of three animals per cage.
    RandomizationSub-chronic ethanol IP treatment: Seven weeks old male Wistar rats (Envigo, Ettlingen, Germany) were randomly distributed in groups and cages of three animals per cage.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Experimental Models: Organisms/Strains
    SentencesResources
    Sub-chronic ethanol IP treatment: Seven weeks old male Wistar rats (Envigo, Ettlingen, Germany) were randomly distributed in groups and cages of three animals per cage.
    Wistar
    suggested: RRID:RGD_150520162)
    Software and Algorithms
    SentencesResources
    Statistica10 (StatSoft) and GraphPad Prism 8.4.3 were used for statistical analysis and graphs.
    GraphPad Prism
    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

  3. Version published to 10.1101/2022.02.01.478685v1 on bioRxiv