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

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dc.contributor.authorKulasinghe, A.
dc.contributor.authorLiu, N.
dc.contributor.authorTan, C.W.
dc.contributor.authorMonkman, J.
dc.contributor.authorSinclair, J.E.
dc.contributor.authorBhuva, D.D.
dc.contributor.authorGodbolt, D.
dc.contributor.authorPan, L.
dc.contributor.authorNam, A.
dc.contributor.authorSadeghirad, H.
dc.contributor.authorSato, K.
dc.contributor.authorBassi, G.L.
dc.contributor.authorO'Byrne, K.
dc.contributor.authorHartmann, C.
dc.contributor.authorDos Santos Miggiolaro, A.F.R.
dc.contributor.authorMarques, G.L.
dc.contributor.authorMoura, L.Z.
dc.contributor.authorRichard, D.
dc.contributor.authorAdams, M.
dc.contributor.authorde Noronha, L.
dc.contributor.authoret al.
dc.date.issued2023
dc.descriptionFirst published: 15 September 2022
dc.description.abstractThe 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.
dc.description.statementofresponsibilityArutha Kulasinghe, Ning Liu, Chin Wee Tan, James Monkman, Jane E. Sinclair, Dharmesh D. Bhuva, David Godbolt, Liuliu Pan, Andy Nam, Habib Sadeghirad, Kei Sato, Gianluigi Li Bassi, Ken O'Byrne, Camila Hartmann, Anna Flavia Ribeiro dos Santos Miggiolaro, Gustavo Lenci Marques, Lidia Zytynski Moura, Derek Richard, Mark Adams, Lucia de Noronha, Cristina Pellegrino Baena, Jacky Y. Suen, Rakesh Arora, Gabrielle T. Belz, Kirsty R. Short, Melissa J. Davis, Fernando Souza-Fonseca Guimaraes, John F. Fraser
dc.identifier.citationImmunology, 2023; 168(3):403-419
dc.identifier.doi10.1111/imm.13577
dc.identifier.issn0019-2805
dc.identifier.issn1365-2567
dc.identifier.orcidLiu, N. [0000-0002-9487-9305]
dc.identifier.orcidBhuva, D.D. [0000-0002-6398-9157]
dc.identifier.orcidDavis, M.J. [0000-0003-4864-7033]
dc.identifier.urihttps://hdl.handle.net/2440/136582
dc.language.isoen
dc.publisherJohn Wiley & Sons
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1157741
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2007919
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1135898
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2008542
dc.rights© 2022 The Authors. Immunology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
dc.source.urihttps://doi.org/10.1111/imm.13577
dc.subjectcardiac
dc.subjectCOVID-19
dc.subjectSARS-CoV-2
dc.subjectspatial profiling
dc.subjecttranscriptomic
dc.titleTranscriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage
dc.typeJournal article
pubs.publication-statusPublished

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