368 - Relation of Immune Profile to Exercise-Induced Pain and Fatigue in [ME/CFS] and Post-acute Sequelae of SARS-CoV-2 Infection, 2025, Berardi et al

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368 - Relation of Immune Profile to Exercise-Induced Pain and Fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-acute Sequelae of SARS-CoV-2 Infection

Giovanni Berardi, Adam Janowski, Samuel McNally, Gregorius Bernhard, Alpana Garg, Kathleen Sluka

Abstract
Individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection (PASC) experience exercise-induced pain and fatigue (EIPF). EIPF can occur during and after exercise and is a barrier to participation in daily activities and exercise. While mechanisms of pain and fatigue are likely multifactorial, several studies suggest a prominent role of the immune system.

This study examined pain, fatigue, and immune cell profiles before and after an exercise task in 30 individuals with PASC, ME/CFS, and controls. Pain and fatigue were assessed prior to and for 7-days following exercise using 0-10 numerical rating scales.

PBMCs were isolated and monocyte, T-cell, natural killer cell, and B-cell phenotypes were characterized using flow cytometry before and after exercise. EIPF was defined as a composite change score for pain and fatigue over 72-hours following exercise and ranged from -4.0-5.3/10 in individuals with ME/CFS and PASC.

There were no differences in monocyte, T-cell, natural killer cell, or B-cell phenotypes at baseline or changes in phenotype following exercise among groups (p>.05).

Cluster analysis identified two distinct groups based on the baseline monocyte phenotype, an inflammatory group (classical monocytes>non-classical monocytes) and a non-inflammatory group (classical monocytes<non-classical monocytes).

The inflammatory group reported higher EIPF (inflammatory: 2.3, non-inflammatory: 0.9, p<.05), and the classical to non-classical monocyte ratio correlated with EIPF (r=.342,p=.05).

These data suggest immune function can drive the pain and fatigue response to an acute bout of exercise and may have implications for future development of anti-inflammatory therapeutics to address EIPF.

Link (The Journal of Pain) [Paywall]
 
Cluster analysis identified two distinct groups based on the baseline monocyte phenotype, an inflammatory group (classical monocytes>non-classical monocytes) and a non-inflammatory group (classical monocytes<non-classical monocytes).

The inflammatory group reported higher EIPF (inflammatory: 2.3, non-inflammatory: 0.9, p<.05), and the classical to non-classical monocyte ratio correlated with EIPF (r=.342,p=.05).
Interesting to see classical monocytes come up again as the main differentiator. Classical monocytes were the type highlighted as most related to disease severity in the Grimson single cell transcriptomics study.
Grimson Paper Abstract said:
At baseline, ME/CFS patients displayed dysregulation of classical monocytes suggestive of inappropriate differentiation and migration to tissue.
https://www.s4me.info/threads/singl...om-provocation-2022-ahmed-hanson-et-al.30170/
 
Link also includes these codes which might link to more information about the study
NIH: R01AR077418, R01AR077418-S1, U24NS112873-S1.
5R01AR077418 = Metabolic Biomarkers for Fibromyalgia
There are 4 publications
https://reporter.nih.gov/search/5-TV32A2Yky37o9D9bvx1w/project-details/10916213#publications

This seems the most relevant publication for ME/CFS - it included 707 individuals with Long Covid, fibromyalgia and CFS with a thought that BPS treatment might help.
Thread : A comparison of pain, fatigue, and function between post-COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study

U24NS112873 = Clinical Coordinating Center for the Acute to Chronic Pain Signatures Program
 
I don't understand why they seem to have invented a new term, EIPF, exercise induced pain and fatigue, rather than any mention of PEM. And assessment of symptoms after the exercise challenge focuses only on pain and fatigue questionnaires.

What about other symptoms worsening and loss of function? If it restriced to was pain and fatigue that increased after exercise, I'd be able to push on when I need to. It's things like nausea, headache, and bad OI and reduced or cancelled ability to function that scuppers me.
 
First one:
Our purpose was to compare two methods of collecting PEM data:
(1) DePaul Symptom Questionnaire – PEM (DSQ-PEM) taken at baseline
and
(2) a sum score of different 0-10 scales measuring physical and mental fatigue, pain, function, and psychological constructs taken pre-exercise and 24hr post-exercise.
Second one:
Aspects of post-exertional malaise, specifically pain and fatigue were assessed prior to, during, and up to 7-days following the exercise bout using 0-10 numerical rating scales.
Given the first one, I had hoped that they realised that you have to account for more than pain and fatigue.
 
I don't understand why they seem to have invented a new term, EIPF,
Bragging rights? Maybe they're hoping for an award for "inventing a new term"? There might also be a benefit by sidestepping arguments against their study based on PEM. "Your arguments about PEM don't apply, since our study is about EIPF."
 
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