Cardiac SARS-CoV-2 infection is associated with pro-inflammatory transcriptomic alterations within the heart
The study titled “Cardiac SARS-CoV-2 infection is associated with pro-inflammatory transcriptomic alterations within the heart” explores the cardiac involvement in COVID-19 and its specific cellular effects. Conducted on 95 autopsy cases with confirmed SARS-CoV-2 infection, it used in situ hybridization, immunohistochemistry, and RNA-sequencing to analyze heart tissue, focusing on virus load and cardiac implications of COVID-19.
- Cardiac SARS-CoV-2 Infection Prevalence: The study found that 43% (41 out of 95) of the deceased exhibited a significant SARS-CoV-2 virus load in the cardiac tissue. These cases showed transcriptomic changes mainly linked to immune response and cardiomyocyte destruction, with endothelial cells being the primary viral targets.
- Gene Expression and Cell Type Analysis: MACE-RNA-sequencing identified 19 differentially expressed genes (DEGs) associated with cardiac SARS-CoV-2 infection. Upregulated genes were linked to interferon pathways originating predominantly from endothelial cells, while downregulated genes were primarily from cardiomyocytes.
- Lack of Increased Immune Cell Infiltration: Contrary to expectations, there was no significant difference in immune cell infiltration in cardiac tissues with or without SARS-CoV-2 infection. This suggests that the virus does not necessarily induce myocarditis in the traditional sense.
- Implications of Myocarditis and Cardiomyocyte Destruction: While traditional signs of myocarditis were not prevalent, the study observed that paracrine effects from cells activated by viral exposure could contribute to cardiomyocyte destruction. This finding aligns with other virus infections that can cause myocardial dysfunction without primarily targeting cardiomyocytes.
- Factors Influencing Cardiac SARS-CoV-2 Infection and Replication: The study revealed a connection between increased TMPRSS2 gene expression and myocardial cell infection and SARS-CoV-2 replication. This suggests a role for TMPRSS2 in mediating cardiac infection, potentially influencing therapeutic strategies with TMPRSS2 inhibitors.
- Association with Shorter Survival Time: A significant finding was that cases with cardiac virus replication showed a shorter time between diagnosis and death, highlighting the severity of cardiac involvement in COVID-19 mortality.
Conclusion: The study underscores the importance of understanding cardiac implications in COVID-19. The cardiac tissue of deceased COVID-19 patients showed significant transcriptomic alterations, especially in endothelial cells, without traditional signs of increased immune cell infiltration. The findings suggest that the cardiac implications of COVID-19, particularly concerning pro-inflammatory responses and cardiomyocyte destruction, are complex and warrant further investigation to fully understand their impact on patient outcomes.