Abstract

Background: 

There is now an urgent need to reduce the burden due to persistent illnesses for patients, health-care providers, governments and economies, which has become so large as to be unfathomable during the current pandemic as the fatiguing symptoms which have worsened them towards disability in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients for close to a century now occur frequently in long COVID patients. 

Materials and methods: 

With the method that permitted Albert Einstein to unravel, with empirical findings, complex phenomena that are beyond the reach of those senses that enable observation and data collection on the path to such findings, we forged the path on which the processes behind the disappearance of such symptoms are to be quantified towards the mechanistic understanding required to develop treatments by which clinicians may achieve the same with precision. 

Results: 

We found that the worsening of persistent illnesses that follows the perception of exertion is not triggered by certain activities or activity levels as logically conceived towards developing the intervention of pacing but rather that the essence of the exertion is the unaffordability of the costs of rendering the decline of energy-generating (mitochondrial) capacity that occurs in the absence of recovery from prior illnesses unapparent. Also, we found that when mitochondrial capacity remains sufficiently high at the onset of the processes behind such unaffordability, patients may still be able to perform strenuous exercise despite the fatiguing worsening of their persistent illnesses so that underperformance is the cardinal symptom that accompanies fatigue while such illnesses are still rendered unapparent, as the case is in those athletes that are diagnosed with overtraining syndrome when anemia and other diagnoses are excluded. Furthermore, we found that when mitochondrial capacity has already approximated nil at this onset, debilitation that follows mere emotional moments may be the consequence of such worsening, as already reported by some ME/CFS patients. Finally, by means of the reduction of serum myoglobin relative to prior values (relative serum myoglobin decline), we verifiably quantified the processes that underlie the progression of the affordability of myoglobin-dependent costs towards the disappearance of the fatiguing symptoms that worsen persistent illnesses and found patients with a particular symptom-based diagnosis heterogeneous with regards to the sufficient progression through which treatment is to reduce the burden due to such illnesses. 

Conclusion: 

The path towards biology-based diagnoses that follow biomedical tests in all patients, which will permit mechanistic understanding of the processes behind fatiguing symptoms that worsen persistent illnesses towards debilitation in some regardless of what they do to pace their activities, is not to be forged through an investigation of post-exercise phenomena in those with onset mitochondrial capacity that is still sufficient for physical activity. Rather, it is that to be forged through the investigation of the phenomena that unify patients with diagnoses that are based on similar progression of those quantified processes that lead to the disappearance of such fatiguing symptoms while symptom content remains difficult to define, even for old symptom-based diagnoses.