Infiltrating monocytes drive cardiac dysfunction in a cardiomyocyte-restricted mouse model of SARS-CoV-2 infection

Heart involvement after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurs in multiple ways and is associated with worse outcomes in coronavirus disease 2019 (COVID-19) patients. It remains unclear if cardiac disease is driven by primary infection of the heart or immune re...

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Published inJournal of virology Vol. 98; no. 9; p. e0117924
Main Authors Dmytrenko, Oleksandr, Das, Shibali, Kovacs, Attila, Cicka, Markus, Liu, Meizi, Scheaffer, Suzanne M., Bredemeyer, Andrea, Mack, Matthias, Diamond, Michael S., Lavine, Kory J.
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 17.09.2024
Subjects
Angiotensin-Converting Enzyme 2 - genetics
Angiotensin-Converting Enzyme 2 - metabolism
Animals
COVID-19 - immunology
COVID-19 - pathology
COVID-19 - virology
Disease Models, Animal
Host-Microbial Interactions
Humans
Macrophages - immunology
Macrophages - virology
Mice
Monocytes - immunology
Monocytes - virology
Myocardium - immunology
Myocardium - pathology
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Myocytes, Cardiac - virology
Pathogenesis and Immunity
SARS-CoV-2
Ventricular Dysfunction, Left - pathology
Ventricular Dysfunction, Left - physiopathology
Ventricular Dysfunction, Left - virology
Virus Replication
ACE2
SARS-CoV-2
murine model
myocarditis
heart
cardiomyocyte
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Summary:Heart involvement after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurs in multiple ways and is associated with worse outcomes in coronavirus disease 2019 (COVID-19) patients. It remains unclear if cardiac disease is driven by primary infection of the heart or immune response to the virus. SARS-CoV-2 is capable of entering contractile cells of the heart in a culture dish. However, it remains unclear how such infection affects the function of the heart in the body. Here, we designed a mouse in which only heart muscle cells can be infected with a SARS-CoV-2 strain to study cardiac infection in isolation from other organ systems. In our model, infected mice show viral infection, worse function, and accumulation of immune cells in the heart. A subset of immune cells facilitates such worsening heart function. As this model shows features similar to those observed in patients, it may be useful for understanding the heart disease that occurs as a part of COVID-19.
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M.S.D. is a consultant for the Advisory Board for Inbios, Vir Biotechnology, IntegerBio, GlaxoSmithKline, Akagera Medicines, Merck, and Moderna. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Emergent BioSolutions, IntegerBio, and Moderna. K.J.L. is a consultant for Implicit Biosciences and Flame Biosciences, is a member of the Medtronic: DT-PAS/APOGEE trial advisory board, and has received funding and unrelated sponsored research agreements from Amgen and Novartis. All other authors have reported that they have no funding and connections relevant to the subject of the manuscript to disclose.
Michael S. Diamond and Kory J. Lavine are joint senior authors.
ISSN:0022-538X
1098-5514
1098-5514
DOI:10.1128/jvi.01179-24