Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: a possible approach to SARS-CoV-2 ‘long-haulers’?, by , Warren Tate in Chronic Dis Transl Med. 2020 Nov 21 [doi: 10.1016/j.cdtm.2020.11.002]

Review article abstract:

A significant number of SARS-CoV-2 (COVID-19) pandemic patients have developed chronic symptoms lasting weeks or months which are very similar to those described for myalgic encephalomyelitis/chronic fatigue syndrome.

This paper reviews the current literature and understanding of the role that mitochondria, oxidative stress and antioxidants may play in the understanding of the pathophysiology and treatment of chronic fatigue. It describes what is known about the dysfunctional pathways which can develop in mitochondria and their relationship to chronic fatigue.

It also reviews what is known about oxidative stress and how this can be related to the pathophysiology of fatigue, as well as examining the potential for specific therapy directed at mitochondria for the treatment of chronic fatigue in the form of antioxidants. This review identifies areas which require urgent, further research in order to fully elucidate the clinical and therapeutic potential of these approaches.

Conclusion

Research into mitochondrial function of ME/CFS has been increasing in recent years and appears to hold potential for better understanding this enigmatic disease that may be increasing its prevalence as a result of the SARS-CoV-2 pandemic. So far, however, the results have proved somewhat contradictory. There are several reasons for this.

An accurate diagnosis for ME/CFS is difficult in the absence a molecular biomarker diagnostic test, individuals in the ME/CFS group are often heterogeneous and have differing disease severity.

There are multiple clinical case definitions that are being used for diagnosis. A vicious circle exists: without a biochemical diagnostic test it is difficult to be certain which patients have ME/CFS and not another fatigue illness with overlapping symptoms, but determining a valid test requires identifying an homogenous group of test subjects.

If ME/CFS is indeed a state of CoQ10 deficiency – particularly in high energy-demand organs like the brain – then an effective way of assessing CoQ10 is needed. This could then be a cellular biomarker that is monitored after oral supplementation in treatment of ME/CFS. Changes in mitochondrial function and markers of oxidative stress may be the biological component most impacted upon by CoQ10 supplementation, due to CoQ10’s vital role in the electron transport chain.

There is also clear need to establish whether MitoQ does indeed improve mitochondrial function and oxidative stress and lessens symptoms in both ME/CFS and chronic symptoms from SARS-CoV-19. There is a biologically plausible mechanism for expected improvement with MitoQ’s superior bioavailability to cells and to mitochondria within them, and by how it can restore oxidative balance and therefore improve mitochondrial function.

A respiratory index, like the BHI, also has the potential to predict and monitor pathophysiology in both ME/CFS and ‘long-haulers’ from SARS-CoV-2. Further research into ME/CFS and SARS-CoV-2, two perplexing and seriously debilitating diseases, is urgently required.