Plasma proteome of Long-COVID patients indicates HIF-mediated vasculo-proliferative disease with impact on brain and heart function (Ioseph, 2023)

[Consul]

Abstract

Aims
Long-COVID occurs after SARS-CoV-2 infection and results in diverse, prolonged symptoms. The present study aimed to unveil potential mechanisms, and to inform prognosis and treatment.

Methods
Plasma proteome from Long-COVID outpatients was analyzed in comparison to matched acutely ill COVID-19 (mild and severe) inpatients and healthy control subjects. The expression of 3072 protein biomarkers was determined with proximity extension assays and then deconvoluted with multiple bioinformatics tools into both cell types and signaling mechanisms, as well as organ specificity.

Results
Compared to age- and sex-matched acutely ill COVID-19 inpatients and healthy control subjects, Long-COVID outpatients showed natural killer cell redistribution with a dominant resting phenotype, as opposed to active, and neutrophils that formed extracellular traps. This potential resetting of cell phenotypes was reflected in prospective vascular events mediated by both angiopoietin-1 (ANGPT1) and vascular-endothelial growth factor-A (VEGFA). Several markers (ANGPT1, VEGFA, CCR7, CD56, citrullinated histone 3, elastase) were validated by serological methods in additional patient cohorts. Signaling of transforming growth factor-β1 with probable connections to elevated EP/p300 suggested vascular inflammation and tumor necrosis factor-α driven pathways. In addition, a vascular proliferative state associated with hypoxia inducible factor 1 pathway suggested progression from acute COVID-19 to Long-COVID. The vasculo-proliferative process predicted in Long-COVID might contribute to changes in the organ-specific proteome reflective of neurologic and cardiometabolic dysfunction.

Conclusions
Taken together, our findings point to a vasculo-proliferative process in Long-COVID that is likely initiated either prior hypoxia (localized or systemic) and/or stimulatory factors (i.e., cytokines, chemokines, growth factors, angiotensin, etc). Analyses of the plasma proteome, used as a surrogate for cellular signaling, unveiled potential organ-specific prognostic biomarkers and therapeutic targets.

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04149-9

 

[pattismith]

I think tissu hypoxia is a key to understand long covid and ME/CFS, but this study is not really interesting for me because they involved post acute covid patients (from intensive care unit), so it's more about post acute covid than long covid patients.

 

[Consul]

@pattismith i read today that a symptom of hypoxia is confusion, thats not a symptom of mecfs as far as i know. In my mind hypoxia is the best explanation of mecfs but not so sure when i read that. What do you think

 

[pattismith]

@pattismith i read today that a symptom of hypoxia is confusion, thats not a symptom of mecfs as far as i know. In my mind hypoxia is the best explanation of mecfs but not so sure when i read that. What do you think

Global Brain hypoxia produced by a sudden drop of arterial O2 (the true hypoxia definition) produces confusion.

It's probably different from chronic effect of endothelial dysfunction in some part of the brain, with different effects and symptoms.

 

[pattismith]

https://www.nature.com/articles/s41598-023-32275-3

• Published: 10 April 2023

Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI​

Abstract​

Cognitive impairment is one of the most prevalent symptoms of post Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) state, which is known as Long COVID. Advanced neuroimaging techniques may contribute to a better understanding of the pathophysiological brain changes and the underlying mechanisms in post-COVID-19 subjects.
We aimed at investigating regional cerebral perfusion alterations in post-COVID-19 subjects who reported a subjective cognitive impairment after a mild SARS-CoV-2 infection, using a non-invasive Arterial Spin Labeling (ASL) MRI technique and analysis.
Using MRI-ASL image processing, we investigated the brain perfusion alterations in 24 patients (53.0 ± 14.5 years, 15F/9M) with persistent cognitive complaints in the post COVID-19 period. Voxelwise and region-of-interest analyses were performed to identify statistically significant differences in cerebral blood flow (CBF) maps between post-COVID-19 patients, and age and sex matched healthy controls (54.8 ± 9.1 years, 13F/9M).

The results showed a significant hypoperfusion in a widespread cerebral network in the post-COVID-19 group, predominantly affecting the frontal cortex, as well as the parietal and temporal cortex, as identified by a non-parametric permutation testing (p < 0.05, FWE-corrected with TFCE).
The hypoperfusion areas identified in the right hemisphere regions were more extensive.
These findings support the hypothesis of a large network dysfunction in post-COVID subjects with cognitive complaints. The non-invasive nature of the ASL-MRI method may play an important role in the monitoring and prognosis of post-COVID-19 subjects.