The plasma metabolome of long COVID-19 patients two years after infection, 2023, Yamille Lopez-Hernandez et al

Abstract
Background: One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as long COVID) which has emerged as a consequence of the SARS-CoV-2 epidemic. The World Health Organization (WHO) recognized long COVID as a distinct clinical entity in 2021. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. This has put a tremendous strain on still-overstretched healthcare systems around the world.

Methods: In this study, our goal was to assess the plasma metabolome in a total of 108 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin concentrations were measured in long COVID patients by immunoenzymatic assay.

Results: The comparison of paired COVID-19/post-COVID-19 samples revealed 53 metabolites that were statistically different (FDR < 0.05). Compared to controls, 29 metabolites remained dysregulated even after two years. Notably, glucose, kynurenine, and certain acylcarnitines continued to exhibit altered concentrations similar to the COVID-19 phase, while sphingomyelins and long saturated and monounsaturated LysoPCs, phenylalanine, butyric acid, and propionic acid levels normalized. Post-COVID-19 patients displayed a heterogeneous metabolic profile, with some showing no symptoms while others exhibiting a variable number of symptoms. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, sarcosine, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients.

Conclusions: Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.

https://www.medrxiv.org/content/10.1101/2023.05.03.23289456v1

 

https://twitter.com/user/status/1654695890114973698

 

https://twitter.com/user/status/1654737068407283712

 

The study has now been published in Nature https://www.nature.com/articles/s41598-023-39049-x.

 

CIDRAP Long-COVID patients have altered metabolite levels 2 years after infection

quote:

"Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection," the study authors wrote.

They said metabolic information may partially explain the differences in disease presentation among long-COVID patients. "Metabolomics is not only useful in providing a snapshot of transient physiological or pathophysiological processes taking place in a living organism, but it has also proven to be a powerful tool for proposing and monitoring therapeutic interventions," they wrote.

 

So what does it say that those are all pretty much the same old hypotheses that never seem to produce actionable results.

They do seem like the explanations, all of them, some of them, one of them, varying between people, but it's a comment we see often on the forum, that it's always the same hypotheses, and they sure do make sense, but it never leads anywhere in terms of changing outcomes, finding biomarkers and therapeutic targets.

We seem to be waiting on basic research to catch up, except basic research is a crapshoot, rarely seems to target specific conditions. Like there's a disconnect between observation/hypothesis and actually working back what it fundamentally means. Especially as those come up pretty much in hundreds of diseases and conditions.

It looks like there are so many clues but no one with the kind of mandate that can work out the full picture of the puzzle and hone in on it. Which is what the $1.15 NIH funding should have done, but they don't seem capable of even thinking this way.