Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis

Area of Science:

• Cardiovascular Science
• Infectious Disease
• Genomics

Background:

• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is linked to cardiovascular events, but the roles of endothelial and myocardial infection are debated.
• The precise mechanisms driving COVID-19-associated cardiovascular complications remain unclear.

Purpose of the Study:

• To investigate coronary endothelial and myocardial programming in severe COVID-19 using digital spatial transcriptomics.
• To analyze the in situ transcriptional changes within cardiac tissue during SARS-CoV-2 infection.

Main Methods:

• Spatial transcriptomic profiling of autopsy-derived cardiac tissue from COVID-19 (n=8) and control (n=4) patients.
• Assessment of differential gene expression in myocardial and coronary vascular tissues.
• Analysis of SARS-CoV-2 paracrine effects within the cardiac microenvironment.

Main Results:

• Heterogeneous myocardial infection observed, often colocalizing with capillary endothelial cells (CD31+).
• COVID-19 patients exhibited a distinct myocardial transcriptional profile, irrespective of viral load.
• Infected cells, primarily capillary endothelial cells, showed pro-inflammatory profiles with upregulated immune mediators.
• Limited transcriptional changes were found in the endothelium of larger coronary vessels.

Conclusions:

• Severe COVID-19 is associated with altered myocardial programming, potentially involving capillary endothelial cells.
• The findings suggest endotheliitis and endothelial activation in larger vessels are less likely drivers of COVID-19 cardiovascular events.