Oxidative Stress is a shared characteristic of ME/CFS and Long COVID, 2024, Shankar, Bonilla, Davis et al.

Now that it's published I am having a proper read. I am writing an experimental paper at the moment that is likely to have a section very relevant to some of the results (results specifically, interpretation is trickier). Still cooking but interesting.

Onto some specifics from this paper that I am not sure about:

I don't see anything about whether mitochondrial membrane potential as measured by mito red fluorescence was normalised to mitochondrial membrane mass. Doesn't seem like it? If it's not, MMP can easily reflect differences in cellular mitochondrial content and not differences in the MMP itself. Without knowing whether they have done this I don't know how to interpret this data.

"We found significantly lower lipid droplet levels in both LC and ME/CFS donors across all measured lymphocyte populations (SI Appendix, Fig. S4D). Both ME/CFS and LC males and females exhibited significantly lower lipid droplet levels (Fig. 5E), "

Measured by whole-cell fluorescence when stained by a neutral lipid dye. These dyes will light up LDs for imaging but if you're putting the whole cell through flow you're probably quantifying any neutral lipid that is getting stained - majority are probably in LDs but not all. Lymphoid cells do not have many lipid droplets relative to other cell types so the impact of this could be exacerbated in this case. I don't know enough about chemistry to judge the dye being used at a glance but it's described by the manufacturer and other papers as a neutral lipid dye so this risk seems realistic.

"One possibility is that this lymphocyte dysfunction, driven by oxidative and mitochondrial damage, acts as an “energy sink,” much as an active infection does, draining the body of its available finite energy reserves and giving rise to debilitating fatigue and other sequelae."

Is there evidence for activity- and diet-independent wasting in pwME?
 
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DMissa said:
"One possibility is that this lymphocyte dysfunction, driven by oxidative and mitochondrial damage, acts as an “energy sink,” much as an active infection does, draining the body of its available finite energy reserves and giving rise to debilitating fatigue and other sequelae."
Click to expand...

DMissa said:
Is there evidence for activity- and diet-independent wasting in pwME?
Click to expand...

I am less familiar with bioenergetic studies but this would be my thought too.

If unhappy lymphocytes were 'draining' energy from the rest of the body surely there should either be loss of weight or, perhaps more immediately, low levels of nutrients like glucose or oxygen in blood? To me this sort of argument isn't really plausible. There isn't any 'energy' floating about that cells can grab other than these measurable things is there?

And we come back to the point that symptoms of MECFS and PEM in particular are not just 'fatigue' and even if they were there isn't much evidence for fatigue being mediated by lack of energy supplies. You can be fatigued with normal glucose and oxygen levels in your blood.
 
Anthony L. Komaroff has written a commentary in the same journal edition based on the paper of the thread:

Growing recognition of post-acute infection syndromes

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID affect large numbers of people, and constitute a substantial burden to the U.S. and global economies. The article by Eckey et al., in this issue of PNAS (1), adds to the growing evidence that the two illnesses have much in common. Moreover, the illnesses may represent just two examples of an even larger, recently recognized class of illness: post-acute infection syndromes (PAIS) (2).

 
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