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

Methods

Autopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue.

Results: We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation.

Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels. Conclusions: Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells.

However, similar patterns were not observed in larger vessels, diminishing endotheliitis and endothelial activation as key drivers of cardiovascular events during COVID-19. Dataset Description: Tab 1: RNA Sequencing results from all myocardial samples organized by patient COVID19 status. These results are independent of spatial location.

Tab 2: RNA Sequencing results from all coronary endothelial samples organized by patient COVID19 status. These results are spatially-resolved to include only the endothelium. Tab 3: RNA Sequencing results from myocardial samples organized by SARS-CoV-2 nucleocapsid expression (Positive vs. Negative immunostain).

These results are spatially-resolved and segmented to highlight sequencing from SARS-CoV-2 infected cells.