What Triggers Fatigue During Illness: Understanding the Pathophysiology?

[mktsgm]

TL;DR Summary

What events trigger fatigue during an illness and how?

What is the mechanism of Fatigue what events initiate it and how?

The trigger of a fever, called a pyrogen, results in the release of prostaglandin E2 (PGE2)

Generally just as a pyrogen such as PGE2 (or LPS) sets thermogenesis in motion, leading to a fever, what kind of events are triggered in physical and mental fatigue during an illness?

I want to know the basic pathophysiology or the sequence of events that are triggered to cause fatigue or tiredness during an illness.

Thanks in advance,

 

[phinds]

What research have you done on this yourself? What have you found?

 

[mktsgm]

What research have you done on this yourself? What have you found?

By fatigue, I mean the feeling of loss of energy.

Since ATP is the currency of energy, low ATP levels may be the underlying reason for fatigue.

Normally, as in a chronic fatigue syndrome, mitochondrial dysfunction may be suspected.

After going through a lot of NCBI articles on fatigue, I think this article gave me overall input on fatigue

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136529/

But, I feel during an illness (especially during/after a viral infection) somehow the process of inflammation may also be involved in fatigue and malaise.

In the Covid situation, for example, some had fever and fatigue/malaise during acute phase and some later had fatigue-only continuing for months, as long covid. Fatigue is found common both in acute and long covid. It is common in all other illnesses too.

So, I want to know how the immune system is involved in fatigue during an illness? Is any particular immune pathway (like complement, T-cell, macrophage activation) more involved in fatigue during an illness? If so, what and how, also...

 

[atyy]

Not what you are asking, but here's another reference that may be related.

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001643
Adverse effects following anti-COVID-19 vaccination with mRNA-based BNT162b2 are alleviated by altering the route of administration and correlate with baseline enrichment of T and NK cell genes.
Syenina A, Gan ES, Toh JZN, de Alwis R, Lin LZ, Tham CYL, Yee JX, Leong YS, Sam H, Cheong C, Teh YE, Wee ILE, Ng DHL, Chan KR, Sim JXY, Kalimuddin S, Ong EZ, Low JG, Ooi EE.

"Herein, we found that higher baseline expression of genes related to T and NK cell exhaustion and suppression were positively correlated with the development of moderately severe fatigue after Pfizer-BioNTech BNT162b2 vaccination; increased expression of genes associated with T and NK cell exhaustion and suppression reacted to vaccination were associated with greater levels of innate immune activation at 1 day postvaccination."

 

[atyy]

Maybe also related

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479364/
Neurobiological studies of fatigue
Mary E. Harrington

https://journals.sagepub.com/doi/10.1177/1073858420985447
The Neurobiology of Pathological Fatigue: New Models, New Questions
Annapoorna Kuppuswamy