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ME/CFS Science
@mecfsscience.org

1) Spanish researchers exposed muscle cells to serum of ME/CFS and Long Covid patients and found: - reduction in muscle contraction strength - upregulation of genes involved in protein translation - elevated oxygen consumption

ME/CFS Science
@mecfsscience.org

2) It looks like the 'something in the blood' hypothesis is back on the table: serum of patients caused cellular stress that serum of healthy controls did not. The sample size was really small though: serum of only 4 ME/CFS patients and 5 Long Covid patients was used.

ME/CFS Science
@mecfsscience.org

3) The researchers developed 3D skeletal muscle tissue in the lab and exposed it for 48 hours to sera of patients (ME/CFS and LC patients) or controls. They replicated the experiment a couple of times per serum sample (these are probably the white open dots in the graphs).

ME/CFS Science
@mecfsscience.org

5) The authors used RNA sequencing to get a glimpse of the activity happening in the muscle cells. There was upregulation of genes involved in protein translation and extracellular matrix and downregulation of those involved in basic organelle functions.

ME/CFS Science
@mecfsscience.org

6) They also found that muscle fibers became larger (hypertrophy) and that mitochondria fused together into different shapes. According to the authors, this all points to cellular stress and altered metabolic activity caused by ME/CFS and LC serum.

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ME/CFS Science
@mecfsscience.org

7) When they exposed the muscle cells to serum of patients for a longer period (96–144 hours), they found it caused muscle fragility and weakness, with mitochondria fragmenting.

ME/CFS Science
@mecfsscience.org

8) This study also reports an increase in the overall oxygen consumption rate which seems to contradict findings from a bigger study that failed to replicate the 'something in the blood' hypothesis and reported no difference in oxygen consumption. www.biorxiv.org/cont...

biorxiv.orgIndistinguishable mitochondrial phenotypes after exposure of healthy myoblasts to myalgic encephalomyelitis or control serumMyalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome is a disease of uncertain aetiology that affects up to 400,000 individuals in the UK. Exposure of cultured cells to the sera of people with ME has been proposed to cause phenotypic changes in these cells in vitro when compared to sera from healthy controls. ME serum factors causing these changes could inform the development of diagnostic tests. In this study, we performed a large-scale, pre-registered replication of an experiment from [Fluge et al (2016)][1] that reported an increase in maximal respiratory capacity in healthy myoblasts after treatment with serum from people with ME compared to serum from healthy controls. We replicated the original experiment with a larger sample size, using sera from 67 people with ME and 53 controls to treat healthy cultured myoblasts, and generated results from over 1,700 mitochondrial stress tests performed with a Seahorse Bioanalyser. We observed no significant differences between treatment with ME or healthy control sera for our primary outcome of interest, oxygen consumption rate at maximal respiratory capacity. Results from our study provide strong evidence against the hypothesis that ME blood factors differentially affect healthy myoblast mitochondrial phenotypes in vitro . ### Competing Interest Statement The authors have declared no competing interest. Action for ME, https://ror.org/0569v7v35, Clare Francis Research Fellowship [1]: #ref-10
ME/CFS Science
@mecfsscience.org

9) Someone pointed out that the difference may be due to the muscle tissue preparation (rather than using isolated muscle cells) which could include secreted extracellular matrix components. These could play a role in the pathological signal. www.s4me.info/thread...

s4me.infoMetabolic adaptation and fragility in healthy 3-D in vitro skeletal muscle tissues exposed to [CFS] and Long COVID-19 sera, 2025, Mughal+ | Science for MEMetabolic adaptation and fragility in healthy 3-D in vitro skeletal muscle tissues exposed to Chronic Fatigue Syndrome and Long COVID-19 sera. Myalgic...