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.
LINK

 

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