Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia, 2025, Giménez -Orenga

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Brain, Behavior, & Immunity - Health

Available online 4 July 2025, 101058
In Press, Journal Pre-proof

Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia


Karen Giménez -Orenga 1, Justine Pierquin 2, Joanna Brunel 2, Benjamin Charvet 2, Eva Martín-Martínez 3, Margot Lemarinier 4, Steven Fried 4, Alexandre Lucas 4, Hervé Perron 2 5, Elisa Oltra 6
1Doctoral School. Catholic University of Valencia San Vicente Mártir
2Geneuro-Innovation, Bioparc Laënnec, Lyon, France
3National Health Service, Manises Hospital, Valencia, Spain
4Institut des Maladies Métaboliques et Cardiovasculaires, INSERM, University Toulouse III–Paul Sabatier, UMR 1297-I2MC, Toulouse, France
5GeNeuro, Geneva, Switzerland
6Department of Pathology, School of Medicine and Health Sciences, Catholic University of Valencia, C/ Quevedo 2, 46001 Valencia, Spain

Received 10 February 2025, Revised 13 June 2025, Accepted 3 July 2025, Available online 4 July 2025.



https://doi.org/10.1016/j.bbih.2025.101058


ABSTRACT​

Post-COVID-19 condition, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), are characterized by fatigue, pain, shortness of breath, sleep disturbances, cognitive dysfunction and other symptoms, heavily impacting on patients daily functioning.

Moreover, over half of patients end up fulfilling ME/CFS and/or FM clinical criteria after a few months of SARS-CoV-2 infection.

Expression of the toxic human endogenous retrovirus (HERV)-W ENV protein can be induced by viral infection and HERV-W detection was correlated with acute COVID-19 severity and found significantly expressed in post-COVID-19 condition.

This study shows that HERV-W ENV may also be present in prepandemic cases of ME/CFS, FM or co-diagnosed with both clinical criteria, suggesting viral participation in these chronic diseases.

To learn whether associated antiviral mechanisms may also show differing patterns of immunological responses, we measured IgM, IgG, IgA and IgE antibody isotypes against SARS-CoV-2 spike and nucleocapsid antigens, the levels of IL-6, IL-8, IL-10, IFNγ and TNFα cytokines, the level of NfL, a neural damage biomarker, as well as some blood cell markers potentially related with fatigue.

Importantly, some of the measured variables showed a capacity to discriminate post-COVID-19 condition cases from all other participants, with 100% sensitivity and up to 71.9% specificity providing a new tool for a differential diagnosis between diseases or syndromes with so many overlapping clinical symptoms.

Interestingly, the detected markers showed moderate-to-strong correlations with patient symptoms pointing at novel therapeutic opportunities.

KEYWORDS​

HERV-W-ENV
post COVID-19 condition
long COVID-19
SARS-CoV-2
Serology
Immunoglobulins
Cytokines
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Fibromyalgia

 
Post-COVID-19 condition, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), are characterized by fatigue, pain, shortness of breath, sleep disturbances, cognitive dysfunction and other symptoms, heavily impacting on patients daily functioning.
Defining ME/CFS as a PCC is just wrong. And no mention of PEM.
Moreover, over half of patients end up fulfilling ME/CFS and/or FM clinical criteria after a few months of SARS-CoV-2 infection.
That’s also wrong, those studies were not at all suitable to determine the prevalence of ME/CFS in PCC.
 
Defining ME/CFS as a PCC is just wrong. And no mention of PEM.
I don’t think they’re saying ME/CFS is only a sequelae of COVID. They’re just saying that the umbrella terms Long COVID or PCC includes many cases of ME/CFS.

Otherwise they wouldn’t mention non-COVID related cases of ME/CFS. Like this clause in the abstract
prepandemic cases of ME/CFS,
 
I don’t think they’re saying ME/CFS is only a sequelae of COVID. They’re just saying that the umbrella terms Long COVID or PCC includes many cases of ME/CFS.

Otherwise they wouldn’t mention non-COVID related cases of ME/CFS. Like this clause in the abstract
Fair enough. I think I would have worded it differently, though.
 
I'd summarize it as: "There's something going on with the immune systems." The question is "precisely what?" I think there's potential in figuring out what the commonalities are. Is it t-cells, or NK cells, or a specific cytokine or ratio of specific cytokines?
 
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