Transcriptomic profiling of cardiac tissues from SARS‐CoV ‐2 patients identifies DNA damage

  1. Arutha Kulasinghe
  2. Ning Liu
  3. Chin Wee Tan
  4. James Monkman
  5. Jane E. Sinclair
  6. Dharmesh D. Bhuva
  7. David Godbolt
  8. Liuliu Pan
  9. Andy Nam
  10. Habib Sadeghirad
  11. Kei Sato
  12. Gianluigi Li Bassi
  13. Ken O'Byrne
  14. Camila Hartmann
  15. Anna Flavia Ribeiro dos Santos Miggiolaro
  16. Gustavo Lenci Marques
  17. Lidia Zytynski Moura
  18. Derek Richard
  19. Mark Adams
  20. Lucia de Noronha
  21. Cristina Pellegrino Baena
  22. Jacky Y. Suen
  23. Rakesh Arora
  24. Gabrielle T. Belz
  25. Kirsty R. Short
  26. Melissa J. Davis
  27. Fernando Souza‐Fonseca Guimaraes
  28. John F. Fraser

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Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is known to present with pulmonary and extra‐pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS‐CoV‐2 infection is likely to lead to more severe disease, with multi‐organ effects, including cardiovascular disease. SARS‐CoV‐2 has been associated with acute and long‐term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS‐CoV‐2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS‐CoV‐2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1‐like macrophage infiltration in the cardiac tissues of COVID‐19 patients. The DNA damage present in the SARS‐CoV‐2 patient samples, were further confirmed by γ‐H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon‐stimulated genes, in particular interferon and complement pathways, when compared with COVID‐19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS‐CoV‐2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra‐pulmonary organs, including the cardiovascular system of COVID‐19 patients, to delineate the immunopathobiology of SARS‐CoV‐2 infection, and long term impact on health.

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  1. Version published to 10.1111/imm.13577
  2. ScreenIT

    SciScore for 10.1101/2022.03.24.22272732: (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

    Antibodies
    SentencesResources
    Immunohistochemistry and RNAscope (SARS-CoV-2): Immunohistochemistry was performed on a Leica Bond-RX autostainer (Leica Biosystems, US) with antibody targeting SARS-CoV-2 spike protein (Abcam, ab272504) at 2 μg·mL−1
    SARS-CoV-2 spike protein ( Abcam ,
    suggested: None
    Software and Algorithms
    SentencesResources
    In this study the main factor of interest is disease with the main contrasts investigated as COVID19 vs control, pH1N1 vs control and COVID19 vs pH1N1 Gene set enrichment analysis: Gene sets from the Molecular Signatures Database49 (MsigDB, v7.2)
    Gene set enrichment analysis: Gene
    suggested: None
    Hallmarks, C2 (curated gene sets) and C5 (gene ontology terms) categories and KEGG pathways gene sets were obtained using the getMisgdb and appendKEGG functions from the msigdb R package (v1.1.5)49
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    Gene set enrichment analysis (GSEA) were performed using fry from the limma package.
    Gene set enrichment analysis
    suggested: (Gene Set Enrichment Analysis, RRID:SCR_003199)
    limma
    suggested: (LIMMA, RRID:SCR_010943)

    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.

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  3. Version published to 10.1101/2022.03.24.22272732v1 on medRxiv