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Cited by 37COVID-19 Clinical Research StudiesViral Infections and Immunology ResearchSARS-CoV-2 and COVID-19 Research

Cell-Specific Mechanisms in the Heart of COVID-19 Patients

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Tsai, Emily J., Čiháková, Daniela, Tucker, Nathan R.·2023·Circulation Research
DOI 10.1161/circresaha.123.321876PMC PMC10171292
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Abstract

From the onset of the pandemic, evidence of cardiac involvement in acute COVID-19 abounded. Cardiac presentations ranged from arrhythmias to ischemia, myopericarditis/myocarditis, ventricular dysfunction to acute heart failure, and even cardiogenic shock. Elevated serum cardiac troponin levels were prevalent among hospitalized patients with COVID-19; the higher the magnitude of troponin elevation, the greater the COVID-19 illness severity and in-hospital death risk. Whether these consequences were due to direct SARS-CoV-2 infection of cardiac cells or secondary to inflammatory responses steered early cardiac autopsy studies. SARS-CoV-2 was reportedly detected in endothelial cells, cardiac myocytes, and within the extracellular space. However, findings were inconsistent and different methodologies had their limitations. Initial autopsy reports suggested that SARS-CoV-2 myocarditis was common, setting off studies to find and phenotype inflammatory infiltrates in the heart. Nonetheless, subsequent studies rarely detected myocarditis. Microthrombi, cardiomyocyte necrosis, and inflammatory infiltrates without cardiomyocyte damage were much more common. In vitro and ex vivo experimental platforms have assessed the cellular tropism of SARS-CoV-2 and elucidated mechanisms of viral entry into and replication within cardiac cells. Data point to pericytes as the primary target of SARS-CoV-2 in the heart. Infection of pericytes can account for the observed pericyte and endothelial cell death, innate immune response, and immunothrombosis commonly observed in COVID-19 hearts. These processes are bidirectional and synergistic, rendering a definitive order of events elusive. Single-cell/nucleus analyses of COVID-19 myocardial tissue and isolated cardiac cells have provided granular data about the cellular composition and cell type–specific transcriptomic signatures of COVID-19 and microthrombi-positive COVID-19 hearts. Still, much remains unknown and more in vivo studies are needed. This review seeks to provide an overview of the current understanding of COVID-19 cardiac pathophysiology. Cell type–specific mechanisms and the studies that provided such insights will be highlighted. Given the unprecedented pace of COVID-19 research, more mechanistic details are sure to emerge since the writing of this review. Importantly, our current knowledge offers significant clues about the cardiac pathophysiology of long COVID-19, the increased postrecovery risk of cardiac events, and thus, the future landscape of cardiovascular disease.

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  • COVID-19-associated myocarditis involves cardiac damage and inflammation indirectly caused by immune dysregulation.

    “COVID-19-associated myocarditis, where cardiac damage and inflammation are indirectly caused by immune dysregulation”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [24]

    The Myocardium section says inflammatory responses are thought to mediate much endothelial-cell and cardiomyocyte death in COVID-19. But the Abstract distinguishes these cardiac injuries and immune-cell infiltrates from myocarditis, which it reports is rare; the paper does not establish immune dysregulation as the cause of COVID-19-associated myocarditis specifically. Page numbers are not available in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Cardiac inflammation may persist after COVID-19 recovery.

    “cardiac inflammation may persist post-COVID-19 recovery”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [24]

    The section “Long COVID and the Long-Term Cardiovascular Risk of Post–COVID-19 Recovery” (page unavailable) identifies ongoing or reactivated immune-response dysfunction as a possible explanation for long-term cardiac effects after recovery. It does not specifically say that inflammation in the heart persists after recovery; the mechanisms remain unknown. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Tsai, E. J., Čiháková, D., & Tucker, N. R.
Affiliations
  • Columbia University (US)
  • Johns Hopkins University (US)
  • Masonic Medical Research Laboratory (US)
Corresponding author
Tsai, Emily J.
ORCID
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2023-05-12
Volume
132
Issue
10
Pages
1290-1301
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/circresaha.123.321876
PMC
PMC10171292
OpenAlex
W4376129081
Cited by
37
References
7
Citations by year
2026: 8 · 2025: 14 · 2024: 7 · 2023: 8
FWCI
1.75
Type
journal article
Language
en
Update notices
correction (2023-06-22)
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association (COVID-19)
  • Johns Hopkins University (COVID-19)
  • National Institutes of Health (COVID-19)
  • National Heart, Lung, and Blood Institute (K01HL140187, R01HL138528, R01HL136586, R01HL118183)
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
COVID-19 pandemic, SARS-CoV-2, cardiac involvement, myocarditis, pericytes, endothelial cells, myocardial necrosis, microthrombi, immunothrombosis, cardiac troponin, cardiac pathophysiology, long COVID, cell type-specific transcriptomics, viral tropism
MeSH terms
COVID-19, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Heart, Heart Diseases, Humans, Myocarditis, Troponin, Hospital Mortality, Myocytes, Cardiac, Endothelial Cells

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