Transcriptional Differences for COVID-19 Disease Map Genes between Males and Females Indicate a Different Basal Immunophenotype Relevant to the Disease

  1. Tianyuan Liu
  2. Leandro Balzano-Nogueira
  3. Ana Lleo
  4. Ana Conesa

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Abstract

Worldwide COVID-19 epidemiology data indicate differences in disease incidence amongst sex and gender demographic groups. Specifically, male patients are at a higher death risk than female patients, and the older population is significantly more affected than young individuals. Whether this difference is a consequence of a pre-existing differential response to the virus, has not been studied in detail. We created DeCovid, an R shiny app that combines gene expression (GE) data of different human tissue from the Genotype-Tissue Expression (GTEx) project along with the COVID-19 Disease Map and COVID-19 related pathways gene collections to explore basal GE differences across healthy demographic groups. We used this app to study differential gene expression of COVID-19 associated genes in different age and sex groups. We identified that healthy women show higher expression-levels of interferon genes. Conversely, healthy men exhibit higher levels of proinflammatory cytokines. Additionally, young people present a stronger complement system and maintain a high level of matrix metalloproteases than older adults. Our data suggest the existence of different basal immunophenotypes amongst different demographic groups, which are relevant to COVID-19 progression and may contribute to explaining sex and age biases in disease severity. The DeCovid app is an effective and easy to use tool for exploring the GE levels relevant to COVID-19 across demographic groups and tissues.

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  1. Version published to 10.3390/genes11121447
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    SciScore for 10.1101/2020.09.30.321059: (What is this?)

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    Table 1: Rigor

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    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Differential gene expression is calculated using edgeR (Robinson et al., 2010) and multiple testing correction is applied following the Benjamini and Hochberg(BH)method (Benjamini and Hochberg, 1995).
    edgeR
    suggested: (edgeR, RRID:SCR_012802)

    Results from OddPub: Thank you for sharing your code.

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

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  3. Version published to 10.1101/2020.09.30.321059v1 on bioRxiv