Kulasinghe, A.Liu, N.Tan, C.W.Monkman, J.Sinclair, J.E.Bhuva, D.D.Godbolt, D.Pan, L.Nam, A.Sadeghirad, H.Sato, K.Bassi, G.L.O'Byrne, K.Hartmann, C.Dos Santos Miggiolaro, A.F.R.Marques, G.L.Moura, L.Z.Richard, D.Adams, M.de Noronha, L.et al.2022-10-122022-10-122023Immunology, 2023; 168(3):403-4190019-28051365-2567https://hdl.handle.net/2440/136582First published: 15 September 2022The 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.en© 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.cardiacCOVID-19SARS-CoV-2spatial profilingtranscriptomicJournal article10.1111/imm.135772022-10-12623958Liu, N. [0000-0002-9487-9305]Bhuva, D.D. [0000-0002-6398-9157]Davis, M.J. [0000-0003-4864-7033]