Unique Transcriptional Coronary Endothelial Cell Pattern in COVID Unique Transcriptional Coronary Endothelial Cell Pattern in COVID

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The study covered in this summary was published on BioRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaways

  • SARS-CoV-2 myocarditis is predominantly associated with capillaritis, and tissues directly infected with SARS-CoV-2 have unique, pro-inflammatory expression profiles as measured by spatial transcriptomic profiling.

  • Unique regional and viral dependent differences within the myocardium and capillary bed may influence the risk for cardiovascular events associated with SARS-CoV-2 infection.

Why This Matters

  • This is the first study to demonstrate that altered myocardial programming during severe COVID-19 is associated with capillary endothelial cells and not larger coronary vessels, suggesting that endotheliitis and endothelial activation are not likely key drivers of cardiovascular events during severe COVID-19.

Study Design

  • Study participants were mean age 67 years, 75% male, and 67% reported a prior cardiovascular diagnosis.

  • All SARS-CoV-2 participants had chest imaging consistent with findings of pneumonia and positive nucleic acid amplification test (PCR) for SARS-CoV-2 indicating COVID-19 pneumonia.

  • Deceased patients without infection or known cardiovascular disease who died before the existence of SARS-CoV-2 were included as control subjects.

  • Autopsy-derived cardiac tissue from four control patients and eight COVID-19 patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue.

  • Fluorescently labeled anti-SARS-CoV-2 nucleocapsid and anti-CD31 antibodies were combined with the GeoMX Cancer Transcriptome and COVID-19 Immune Response Atlas gene sets with custom probes specific for SARS-CoV-2 lung infection and tissue responses, totaling 1860 genes.

  • 1-way ANOVA or Chi square test were used to measure differences between groups for continuous and categorical values, respectively.

Key Results

  • SARS-CoV-2 infects myocardial tissue with variable expression patterns, most notably in the capillary bed adjacent to the myocardium, with severe COVID-19.

  • SARS-CoV-2 induces a unique spatial transcriptomic profile in the myocardium of patients with COVID-19, independent of local viral load.

  • SARS-CoV-2 induces cell-specific transcriptional patterns in coronary capillary endothelial cells and not in arterial or venous endothelium.

  • Differential programming of the myocardium suggests the coronary capillary bed, and not the arterial or venous systems, is a potential mediator of myocardial injury and cardiovascular events associated with severe COVID-19.

Limitations

  • The study did not assess differences in SARS-CoV-2 variants.

  • A minority of COVID-19 patients had documented thrombotic events and myocardial injury.

  • The study approach fails to definitively identify altered capillary endothelial programming due to limited morphological markers to differentiate pericytes and endothelial cells and the inability to isolate single cells for profiling.

  • Sample size was limited due to use of spatial transcriptomics.

Disclosures

  • Research reported in this publication was supported by the UAB High Resolution Imaging Facility.

  • Lead author Camilla Margaroli, PhD, was supported by the Cystic Fibrosis Foundation. None of the authors disclosed any competing interests.

This is a summary of a preprint research study, “Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis,” written by Camilla Margaroli, PhD, from the University of Alabama at Birmingham, and colleagues on BioRxiv.org provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found at BioRxiv.org.

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