Abstract 15223: Insights into Myocardial Programming in SARS-CoV-2 Infection Using Spatial Transcriptomics

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is linked to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this has sparked growing controversy. Significance of myocardial infection also remains unclear. Hypothesis: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 with digital spatial transcriptomics. 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 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 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 (Figure 1). 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 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.