Chronic fatigue syndrome, long COVID and a metabolic cause

As a neurologist I saw a lot of people who were chronically tired and fatigued, because neurologists deal with muscle weakness and diseases like myasthenia gravis which are associated with fatigue.  Once I ruled out neuromuscular disease as a cause, I had nothing to offer then (nor did medicine).  Some of these patients were undoubtedly neurotic, but there was little question in my mind that many others had something wrong that medicine just hadn’t figured out yet — not that it hasn’t been trying.

Infections of almost any sort are associated with fatigue, most probably caused by components of the inflammatory response.  Anyone who’s gone through mononucleosis knows this.    The long search for an infectious cause of chronic fatigue syndrome (CFS) has had its ups and downs — particularly downs — see https://luysii.wordpress.com/2011/03/25/evil-scientists-create-virus-causing-chronic-fatigue-syndrome-in-lab/

At worst many people with these symptoms are written off as crazy; at best, diagnosed as depressed  and given antidepressants.  The fact that many of those given antidepressants feel better is far from conclusive, since most patients with chronic illnesses are somewhat depressed.

The above 3 paragraphs were written in 2017 when COVID19 was on nobody’s radar.  One definition of long COVID  (there are many) is symptoms persisting longer than 3 months after infection.  The symptoms of long COVID seem identical to chronic fatigue syndrome, and are just another piece of evidence that something is really wrong with these people.  I find this gratifying, and patients should too.

However, very little has turned up in a biochemical, metabolic, neurophysiologic sense to explain the fatigue.  r

One case of longstanding fatigue and exercise intolerance in a 38 year old women does have an explanation [ Proc. Natl. Acad. Sci. vol. 120 e2302738120 ’23 ].  Interestingly, the symptoms began after a case of mononucleosis at age 16.   There was over expression of Wiskott Aldrich Syndrome protein Family member 3 (WASF3 to you) in her muscles.   WASF3 disrupts mitochodrial respiratory supercomplex formation, so that the mitochondria make less ATP than the body needs.  Recall that you make and consume half your body weight of ATP each day.  ATP is where the metabolic rubber meets the road, and as much energy as food can give goes into making it.

Unfortunately the paper claims that immunoblots for WASF3 of 6 patients with chronic fatigue showed elevated levels compared to controls.  They show the blots and I’m unimpressed that there is much difference.

Time for other people to try to replicate this even though the cited work is from NIH