Preprint Autoantibody-Driven Monocyte Dysfunction in Post-COVID Syndrome with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2025, Hackel+

Abstract:
Post-COVID syndrome (PCS) has emerged as a significant health concern with persisting symptoms. A subset of PCS patients develops severe myalgic encephalomyelitis/chronic fatigue syndrome (pcME/CFS). Dysregulated autoantibodies (AABs) have been implicated in PCS, contributing to immune dysregulation, impairment of autonomous nerve and vascular function.

As recently shown in autoimmune diseases, IgG fractions translate disease-specific pathways into various cells. Therefore, we asked whether IgG fractions from PCS patients could be applied in vitro to identify specific cytokine rersponses for PCS patients without (nPCS) and with pcME/CSF. To assess this, we have stimulated monocyte cell lines with IgG fractions from PCS patients. Our findings reveal distinct patterns of immune regulation by AABs in vascular and immune dysfunction.

In contrast to nPCS, pcME/CSF AABs induced enhanced neurotrophic responses, characterized by significant cytokine correlations involving brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and LIGHT. AAB-induced cytokine levels correlate with clinical symptoms. Further, this study emphasizes a contribution of AAB in PCS, in mitigating long-term immune dysregulation, and a need for therapies modulating IgG-induced pathways.

Link | PDF (MedRxiv preprint, open access)

 

I don't see how they know any effects are due to autoantibodies.

 

Interesting that all 24 had "exercise intolerance" but only 12 fit CCC for ME/CFS. Potential false negatives in the other 12 placed in the non-ME/CFS group?


The table says the "disease duration" for healthy controls was 6 months. What does that mean?

Odd that the p value is different (0.306 vs 0.252) when comparing disease duration in years or in months. Should be the same, and seems like a big difference to be due to rounding, but I guess it's possible.

Edit: Other observations about Table 1:

Text says 12 and 12 for sample sizes of the two PCS groups, but the table shows n=13 for many comparisons in nPCS group.

BMI for healthy controls is based on n=1.

 

A single cell RNA study from Andrew Grimson, Germain? (Maureen Hansen group) highlighted monocytes as one of the cell types difference between people with me and healthy controls. I’m not sure if monocyte differences were baseline or pre-/post Max exercise.

Sorry, I’m in no state to find links, but it’s on the forum.

 

Maybe “I’m out of breath going up the stairs” (Lung damage long COVID) and “I feel dizzy and get a headache when exercising” (OI Long COVID) could explain the other exercise intolerance cases.

 

"Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation"

Also related & of interest was "Immunometabolic changes and potential biomarkers in CFS peripheral immune cells revealed by single-cell RNA sequencing"