Systemic analysis of putative SARS-CoV-2 entry and processing genes in cardiovascular tissues identifies a positive correlation of BSG with age in endothelial cells

  1. Blerina Ahmetaj-Shala
  2. Ricky Vaja
  3. Santosh S Atanur
  4. Peter M. George
  5. Nicholas S. Kirkby
  6. Jane A. Mitchell

Reviewed by

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread throughout the world with unprecedented global healthcare and socio-economic consequences. There is now an established secondary syndrome of COVID-19 characterised by thrombosis, vascular dysfunction and hypertension, seen in those most severely affected. Advancing age in adults is the single most significant risk factor for hospitalisation and death with COVID-19. In light of the cardiovascular/thrombotic sequalae associated with severe COVID-19 disease and the overwhelming risk that increased age carries, in this study, our aim was to obtain mechanistic insight by interrogating gene expression profiles in cardiovascular tissues and cells. Our focus was on the two putative receptors for SARS-CoV-2, ACE2 and BSG along with a selected range of genes thought to be involved in virus binding/processing. In this study we have made four important observations: (i)Cardiovascular tissues and/or endothelial cells express the required genes for SARS-CoV-2 infection, (ii) SASR-CoV-2 receptor pathways, ACE2 / TMPRSS2 and BSG / PPIB(A ) polarise to lung/epithelium and vessel/endothelium respectively, (iii) expression of SARS-CoV-2 host genes are, on the whole, relatively stable with age and (iv) notable exceptions were ACE2 which decreases with age in some tissues and BSG which increases with age in endothelial cells. Our data support the idea that that BSG is the dominate pathway utilised by SARS-CoV-2 in endothelial cells and are the first to demonstrate a positive correlation with age. We suggest BSG expression in the vasculature is a critical driver which explains the heightened risk of severe disease and death observed in those >40 years of age. Since BSG is utilised by other pathogens our findings have implications beyond the current pandemic. Finally, because BSG is functions in a range of cardiovascular diseases and fibrosis, our observations may have relevance to our understanding of the diseases associated with aging.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.06.23.165324: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Gene expression dataset systematic review analysis: Using ArrayExpress and NCBI GEO we identified the raw datasets (.
    ArrayExpress
    suggested: (ArrayExpress, RRID:SCR_002964)
    CEL) files were imported into Partek Flow® software and aligned with STAR to the human assembly (hg19) whole genome.
    STAR
    suggested: (STAR, RRID:SCR_015899)
    Statistical analysis: All data were analysed on GraphPad Prism v8 and are shown as mean +/− SEM for samples from ‘n’ = individual donors.
    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 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.

    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 10.1101/2020.06.23.165324 on bioRxiv