Transcriptomic profiling of cardiac tissues from SARS‐CoV‐2 patients identifies DNA damage. Issue 3 (27th September 2022)

• Record Type: Journal Article
• Authors: Kulasinghe, Arutha; Liu, Ning; Tan, Chin Wee; Monkman, James; Sinclair, Jane E.; Bhuva, Dharmesh D.; Godbolt, David; Pan, Liuliu; Nam, Andy; Sadeghirad, Habib; Sato, Kei; Bassi, Gianluigi Li; O'Byrne, Ken; Hartmann, Camila; dos Santos Miggiolaro, Anna Flavia Ribeiro; Marques, Gustavo Lenci; Moura, Lidia Zytynski; Richard, Derek; Adams, Mark; de Noronha, Lucia; Baena, Cristina Pellegrino; Suen, Jacky Y.; Arora, Rakesh; Belz, Gabrielle T.; Short, Kirsty R.; Davis, Melissa J.; Guimaraes, Fernando Souza‐Fonseca; Fraser, John F.
• Is Part Of: Immunology. Volume 168:Issue 3(2023)
• Page Start: 403
• Page End: 419
• Publication Date: 2022-09-27
• Subjects: cardiac -- COVID‐19 -- SARS‐CoV‐2 -- spatial profiling -- transcriptomic; Immunology -- Periodicals
• DOI: 10.1111/imm.13577
• Languages: English
• ISSNs: 0019-2805

Abstract

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. Abstract : Cardiac tissues collected at rapid autopsy from COVID‐19 and pandemic H1N1 patients were profiled using digital spatial profiling technology. The transcriptional profiles were compared and contrasted in the study to understand the impact of viral infection. Host transcriptomics showed distinct transcriptional profiles, such as DNA damage and repair which were upregulated in COVID‐19. The study highlights the need to understand the pathobiology of severe acute respiratory syndrome coronavirus 2 infection and the multi‐organ effects.