CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID, 2024, Dilip Thomas et al

Abstract
Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown.

Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to ‘phenotype switching’ and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction.

These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.
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Copied from News from the USA

10/14/24, Stanford Medicine: "Unraveling the Heart of Long COVID"

'To explore how long COVID impacts heart health, researchers in this study used induced pluripotent stem cells (iPSCs) differentiated into heart muscle cells, or cardiomyocytes (iPSC-CMs).’

"Emerging research about long COVID suggests that influence of the virus extends to the heart through an intricate interplay of immune response, inflammation, and endothelial cell (EC) dysfunction.”

"Endothelial cells have emerged as key players in cardiovascular complications of long COVID, and understanding how they contribute is crucial for developing treatments and preventative strategies.”

"These cells are important for maintaining healthy blood flow and heart function. In long COVID, endothelial cells become inflamed and dysfunctional. They also release too many CCLs, a chemokine that attracts immune cells and promotes inflammation.”

"This important study shows the potential of targeting endothelial dysfunction and the associated inflammatory responses for treatment of existing heart issues or to prevent further cardiovascular complications in long COVID patients.”

"The cutting-edge work presented in this manuscript highlights the importance of continued research to understand the full scope of the effect of long COVID on the body. As health challenges posed by long COVID continue to evolve, it becomes more important to move closer to finding ways to treat or prevent the long-term impact.”

 

I read this paper yesterday and it looks like an important study, but unfortunately paywalled.

There's also commentary in Endothelial cells as paracrine mediators of long COVID (2024, Nature Cardiovascular Research)

I'll quote liberally from that commentary to give people a summary of the main paper. I don't know how much of this might relate to ME/CFS-LC — or non-Covid ME/CFS. I assume this mechanism might explain post-vaccination myocarditis, given they also induced effects via a "non-replicative baculovirus that is pseudotyped with spike protein".

 

Interesting methodology. Very small numbers of patients & controls, though, and worth noting how LC was classified - this is a very different study population to "LC-ME/CFS" cases:

 

LINK