SARS-CoV-2 infection of 3D in vitro cardiac spheroids models the activation of antiviral, inflammatory, fibrotic and contractility responses in a dose-dependent manner.

Johansen, M; Liu Chung Ming, C; Hansbro, PM; Gentile, C

SARS-CoV-2 infection of 3D in vitro cardiac spheroids models the activation of antiviral, inflammatory, fibrotic and contractility responses in a dose-dependent manner.

Johansen, M

Liu Chung Ming, C Hansbro, PM Gentile, C

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Publisher:: IOP Publishing
Publication Type:: Journal Article
Citation:: Biofabrication, 2026
Issue Date:: 2026-01-15

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Field	Value	Language
dc.contributor.author	Johansen, M https://orcid.org/0000-0001-5553-5270
dc.contributor.author	Liu Chung Ming, C
dc.contributor.author	Hansbro, PM
dc.contributor.author	Gentile, C https://orcid.org/0000-0002-3689-4275
dc.date.accessioned	2026-01-27T14:50:09Z
dc.date.available	2026-01-27T14:50:09Z
dc.date.issued	2026-01-15
dc.identifier.citation	Biofabrication, 2026
dc.identifier.issn	1758-5082
dc.identifier.issn	1758-5090
dc.identifier.uri	http://hdl.handle.net/10453/192447
dc.description.abstract	The emergence of SARS-CoV-2 in 2019 led to a global pandemic with severe respiratory symptoms and substantial extrapulmonary manifestations. Increasing evidence suggests significant cardiovascular complications associated with SARS-CoV-2 infection, which are critical factors in morbidity and mortality. In this study, we assessed the viral infectivity and viral niche of SARS-CoV-2 using our clinically-amenablein vitrocardiac spheroids (CSs), which have previously been demonstrated to be an optimal tool to recapitulate the complex cardiac pathophysiology. We examined the expression profiles of cardiovascular-related disease genes and pathways involved in inflammation, interferon responses, and antiviral defence following infection. Genes associated with apoptosis, chemotaxis, fibrosis, and contractile function exhibited substantial increases, implicating these pathways in the cardiac response to SARS-CoV-2. Furthermore, our 3D rendering analyses using confocal imaging revealed cell-specific effects mediated by the virus by colocalising SARS-CoV-2 nucleocapsid protein with each cell type, supporting the ability of CSs to facilitate viral replication and contributing to the observed phenotypes. Additionally, SARS-CoV-2 could only infect intact CSs, whereas it did not infect individual cell types cultured individually. The unique ability of CSs to model SARS-CoV-2 in the heart may potentially mirror the pathophysiological changes observed in COVID-19-induced cardiac complications. Altogether, our results suggest that CSs offer a valuable tool for dissecting direct host-viral interactions and advancing our understanding of SARS-CoV-2-related cardiac injury. Our findings underscore the utility of CSs in revealing the mechanisms of SARS-CoV-2-induced cardiac damage and provide a basis for further studies into the long-term cardiovascular consequences of SARS-CoV-2.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	IOP Publishing
dc.relation.ispartof	Biofabrication
dc.relation.isbasedon	10.1088/1758-5090/ae38d7
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0903 Biomedical Engineering, 1004 Medical Biotechnology, 1099 Other Technology
dc.subject.classification	3206 Medical biotechnology
dc.subject.classification	4003 Biomedical engineering
dc.title	SARS-CoV-2 infection of 3D in vitro cardiac spheroids models the activation of antiviral, inflammatory, fibrotic and contractility responses in a dose-dependent manner.
dc.type	Journal Article
utslib.location.activity	England
utslib.for	0903 Biomedical Engineering
utslib.for	1004 Medical Biotechnology
utslib.for	1099 Other Technology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Inflammation (CFI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Chancellor's Research Fellows
pubs.organisational-group	University of Technology Sydney/UTS Groups/UTS LGBTIQA+ Research Network
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-01-27T14:48:49Z
pubs.publication-status	Published online

Abstract:

The emergence of SARS-CoV-2 in 2019 led to a global pandemic with severe respiratory symptoms and substantial extrapulmonary manifestations. Increasing evidence suggests significant cardiovascular complications associated with SARS-CoV-2 infection, which are critical factors in morbidity and mortality. In this study, we assessed the viral infectivity and viral niche of SARS-CoV-2 using our clinically-amenablein vitrocardiac spheroids (CSs), which have previously been demonstrated to be an optimal tool to recapitulate the complex cardiac pathophysiology. We examined the expression profiles of cardiovascular-related disease genes and pathways involved in inflammation, interferon responses, and antiviral defence following infection. Genes associated with apoptosis, chemotaxis, fibrosis, and contractile function exhibited substantial increases, implicating these pathways in the cardiac response to SARS-CoV-2. Furthermore, our 3D rendering analyses using confocal imaging revealed cell-specific effects mediated by the virus by colocalising SARS-CoV-2 nucleocapsid protein with each cell type, supporting the ability of CSs to facilitate viral replication and contributing to the observed phenotypes. Additionally, SARS-CoV-2 could only infect intact CSs, whereas it did not infect individual cell types cultured individually. The unique ability of CSs to model SARS-CoV-2 in the heart may potentially mirror the pathophysiological changes observed in COVID-19-induced cardiac complications. Altogether, our results suggest that CSs offer a valuable tool for dissecting direct host-viral interactions and advancing our understanding of SARS-CoV-2-related cardiac injury. Our findings underscore the utility of CSs in revealing the mechanisms of SARS-CoV-2-induced cardiac damage and provide a basis for further studies into the long-term cardiovascular consequences of SARS-CoV-2.

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http://hdl.handle.net/10453/192447