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

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 govern this remain unknown. In this study, we investigated the landscape of cardiac tissues collected at rapid autopsy from SARS-CoV-2, pH1N1, and 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 gamma-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of Interferon-stimulated genes (ISGs), 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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Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

“…A sophisticated spatio-temporal analysis of host transcriptomics from autopsy samples of cardiac tissues obtained from COVID-19 patients revealed that, although absent in cardiac tissues, SARS-CoV-2 can cause extensive DNA damage and the consequential upregulation of genes associated with DNA damage repair. Whereas the downregulation of gene clusters associated in mitochondrial function and metabolic regulation in cardiac tissues may be responsible for the evasion of mitochondria-mediated innate immunity [ 753 ]. The SARS-CoV-2 virus spike protein may cause dysregulation of DNA damage response by preventing the recruitment of key DNA repair proteins, including the E3 ubiquitin ligase Breast Cancer 1 (BRCA1) to targeted damage sites [ 754 , 755 ].…”

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