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

Kulasinghe, A; Liu, N; Tan, CW; Monkman, J; Sinclair, JE; Bhuva, DD; Godbolt, D; Pan, L; Nam, A; Sadeghirad, H; Sato, K; Bassi, GL; O&#39;Byrne, K; Hartmann, C; Miggiolaro, Afrds; Marques, GL; Moura, LZ; Richard, D; Adams, M; Noronha, L; Baena, CP; Suen, JY; Arora, R; Belz, GT; Short, KR; Davis, MJ; Souza-Fonseca Guimaraes, F; Fraser, JF

Author(s): Kulasinghe, A; Liu, N; Tan, CW; Monkman, J; Sinclair, JE; Bhuva, DD; Godbolt, D; Pan, L; Nam, A; Sadeghirad, H; Sato, K; Bassi, GL; O'Byrne, K; Hartmann, C; Miggiolaro, Afrds; Marques, GL; Moura, LZ; Richard, D; Adams, M; Noronha, L; Baena, CP; Suen, JY; Arora, R; Belz, GT; Short, KR; Davis, MJ; Souza-Fonseca Guimaraes, F; Fraser, JF;
Details: Publication Year 2023-09-15,Volume 168,Issue #3,Page 403-419
Journal Title: Immunology
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.
Publisher: Wiley
Keywords: Covid-19; SARS-CoV-2; cardiac; spatial profiling; transcriptomic
Research Division(s): Bioinformatics
PubMed ID: 36107637
Publisher's Version: https://doi.org/10.1111/imm.13577
Open Access at Publisher's Site: https://doi.org/10.1111/imm.13577
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2022-09-19 02:39:13

Last Modified: 2023-06-09 10:43:02