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

Margaroli, C; Benson, P; Gastanadui, MG; et al., Frontiers in Medicine, March 2023

View Publication on PubMed

March 2023
Frontiers in Medicine

Short Summary

COVID-19 can damage the heart in ways that doctors are still working to understand. Some people develop heart problems during or after COVID-19 infection, including inflammation of the heart muscle. To better understand how the virus affects the heart, researchers studied heart tissue from people who died with COVID-19. They wanted to learn what happens to the blood vessels in the heart during infection.

The research team examined heart tissue samples from autopsies using advanced techniques. These methods allowed them to see which genes were active in different parts of the tissue. They focused on cells that line the inside of blood vessels in the heart. The researchers compared tissue from 8 people who had COVID-19 to tissue from 4 people who died from other causes. They found that, in people with COVID-19, the blood vessel cells showed signs of stress and inflammation. These cells had turned on genes related to fighting infection and responding to injury. The team also found evidence of the virus itself in some heart tissue samples.

These findings help explain why some people have heart problems after COVID-19. The virus appears to directly affect blood vessels in the heart, causing inflammation and damage. Understanding these changes at the cellular level may lead to new ways to prevent or treat heart problems in Long COVID.

This summary was prepared by the RECOVER Initiative.

Publication Details

DOI: 10.3389/fmed.2023.1118024

Abstract

Objectives: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear.

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.

Conclusion: 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.

Authors

Camilla Margaroli, Paul Benson, Maria G Gastanadui, Chunyan Song, Liliana Viera, Dongqi Xing, J Michael Wells, Rakesh Patel, Amit Gaggar, Gregory A Payne

Keywords

cell programming; endothelium; myocarditis; severe acute respiratory syndrome coronavirus-2; spatial transcriptomic