tetano
Editor, Senior Moderator
Immunology
. 2022 Sep 15.
doi: 10.1111/imm.13577. Online ahead of print.
Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage
Arutha Kulasinghe[SUP] 1 [/SUP], Ning Liu[SUP] 2 3 [/SUP], Chin Wee Tan[SUP] 2 3 [/SUP], James Monkman[SUP] 1 [/SUP], Jane E Sinclair[SUP] 4 [/SUP], Dharmesh D Bhuva[SUP] 2 3 [/SUP], David Godbolt[SUP] 5 [/SUP], Liuliu Pan[SUP] 6 [/SUP], Andy Nam[SUP] 6 [/SUP], Habib Sadeghirad[SUP] 1 [/SUP], Kei Sato[SUP] 7 [/SUP], Gianluigi Li Bassi[SUP] 7 [/SUP], Ken O'Byrne[SUP] 8 [/SUP], Camila Hartmann[SUP] 9 10 [/SUP], Anna Flavia Ribeiro Dos Santos Miggiolaro[SUP] 9 10 [/SUP], Gustavo Lenci Marques[SUP] 9 10 [/SUP], Lidia Zytynski Moura[SUP] 9 10 [/SUP], Derek Richard[SUP] 11 [/SUP], Mark Adams[SUP] 11 [/SUP], Lucia de Noronha[SUP] 9 [/SUP], Cristina Pellegrino Baena[SUP] 9 10 [/SUP], Jacky Y Suen[SUP] 7 [/SUP], Rakesh Arora[SUP] 12 [/SUP], Gabrielle T Belz[SUP] 1 [/SUP], Kirsty R Short[SUP] 3 [/SUP], Melissa J Davis[SUP] 2 13 [/SUP], Fernando Souza-Fonseca Guimaraes[SUP] 1 [/SUP], John F Fraser[SUP] 5 [/SUP]
Affiliations
Abstract
Aims: 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 govern this remain unknown. To investigate the host transcriptome changes of cardiac tissues from patients who died from COVID-19, pH1N1, and healthy cardiac tissues.
Methods and results: In this study, we investigated the landscape of cardiac tissues collected at rapid autopsy from 7 SARS-CoV-2, 2 pH1N1, and 6 control patients using targeted spatial transcriptomics approaches. The main outcomes for the study were to profile rapid autopsy samples collected from the COVID-19, pH1N1 and normal, non-viral deaths to determine transcriptional changes between the different cohorts. 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 (ISGs), in particular interferon and complement pathways, when compared with COVID-19 patients.
Conclusion: 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.
Keywords: COVID-19; SARS-CoV-2; cardiac; spatial profiling; transcriptomic.
. 2022 Sep 15.
doi: 10.1111/imm.13577. Online ahead of print.
Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage
Arutha Kulasinghe[SUP] 1 [/SUP], Ning Liu[SUP] 2 3 [/SUP], Chin Wee Tan[SUP] 2 3 [/SUP], James Monkman[SUP] 1 [/SUP], Jane E Sinclair[SUP] 4 [/SUP], Dharmesh D Bhuva[SUP] 2 3 [/SUP], David Godbolt[SUP] 5 [/SUP], Liuliu Pan[SUP] 6 [/SUP], Andy Nam[SUP] 6 [/SUP], Habib Sadeghirad[SUP] 1 [/SUP], Kei Sato[SUP] 7 [/SUP], Gianluigi Li Bassi[SUP] 7 [/SUP], Ken O'Byrne[SUP] 8 [/SUP], Camila Hartmann[SUP] 9 10 [/SUP], Anna Flavia Ribeiro Dos Santos Miggiolaro[SUP] 9 10 [/SUP], Gustavo Lenci Marques[SUP] 9 10 [/SUP], Lidia Zytynski Moura[SUP] 9 10 [/SUP], Derek Richard[SUP] 11 [/SUP], Mark Adams[SUP] 11 [/SUP], Lucia de Noronha[SUP] 9 [/SUP], Cristina Pellegrino Baena[SUP] 9 10 [/SUP], Jacky Y Suen[SUP] 7 [/SUP], Rakesh Arora[SUP] 12 [/SUP], Gabrielle T Belz[SUP] 1 [/SUP], Kirsty R Short[SUP] 3 [/SUP], Melissa J Davis[SUP] 2 13 [/SUP], Fernando Souza-Fonseca Guimaraes[SUP] 1 [/SUP], John F Fraser[SUP] 5 [/SUP]
Affiliations
- PMID: 36107637
- DOI: 10.1111/imm.13577
Abstract
Aims: 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 govern this remain unknown. To investigate the host transcriptome changes of cardiac tissues from patients who died from COVID-19, pH1N1, and healthy cardiac tissues.
Methods and results: In this study, we investigated the landscape of cardiac tissues collected at rapid autopsy from 7 SARS-CoV-2, 2 pH1N1, and 6 control patients using targeted spatial transcriptomics approaches. The main outcomes for the study were to profile rapid autopsy samples collected from the COVID-19, pH1N1 and normal, non-viral deaths to determine transcriptional changes between the different cohorts. 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 (ISGs), in particular interferon and complement pathways, when compared with COVID-19 patients.
Conclusion: 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.
Keywords: COVID-19; SARS-CoV-2; cardiac; spatial profiling; transcriptomic.