COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status, 2020, Thomas et al

Andy

Andy

Retired committee member
Reprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks. To investigate metabolic effects of SARS-COV-2 infection, we evaluated serum metabolites of COVID-19 patients (n = 33; diagnosed by nucleic acid testing), as compared to COVID-19-negative controls (n = 16).

Targeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).

In conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.
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Open access, https://insight.jci.org/articles/view/140327/pdf
 
A depletion of tryptophan and an increase in the kynurenine pathway. That seems part of a normal response to an infection.

But maybe, if the metabolic trap hypothesis is correct, and this particular virus provokes a particularly strong activation of the kynurenine pathway, then it could be good at causing the metabolic trap.

This part is also mildly interesting:

In addition, sera from COVID-19 patients demonstrated significant changes in levels of acylcarnitines and free fatty acids (Figure 6). Specifically, all short and medium-chain acylcarnitines, but not acyl-C18:3, were significantly decreased in all COVID-19 patients, independent of IL-6 levels.
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I'm too tired to read the entire article.
 
Someone on Twitter linked this paper and suggested it shows "Covid patients are found to have elevated hydroxyproline levels, which indicates the degradation of collagen/connective tissue" and suggests this is leading to structural spinal problems that may need surgery.

I had a quick look through the paper but didn't find mention of hydroxyproline. If anyone else has the energy to look, I'd be interested in your comments.
 
No comments on it, but top of page 6 in the indented paragraph:

"Although no significant changes were noted in methionine levels, increases in acetyl-methionine and hydroxyproline, by-products of proteolysis and collagen catabolism, respectively, were observed, particularly in patients with COVID-19 with the highest IL-6 levels (Figure 4B). D"

and top of page 10:

"It is worth noting that proinflammatory signaling favors proteolysis and amino acid catabolism (represented herein by increased acetyl-methionine and hydroxyproline and altered levels of free amino acids), which can be antagonized, in part, by antiinflammatory cytokines (e.g., IL-37) (54) or inflammasome inhibitors (55)."
 
Thanks @Tao Fogger. My lay person's response is that this is data collected from a small sample of people while they have acute Covid infection. Any extrapolation to long covid seems stretching the point way too far.
 
From the little I read of the paper (very little - I don't have the brain cells to make sense of it), it certainly seems quite a leap to draw the conclusions the twitter poster you quoted said @Trish
 
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