Tag: long Covid

A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID (LC) are increasingly recognized as debilitating postinfectious conditions that impact both individuals and society. Recent research highlights the potential of metformin, an antidiabetic agent, as a treatment for these syndromes by targeting their underlying mechanisms. This review assesses the effectiveness of metformin in ME/CFS and LC, which involve complex dysfunctions related to cytokines, glycolysis, ATP generation, oxidative stress, gastrointestinal microbiomes, and vascular endothelial function.

Metformin, traditionally known for its antihyperglycemic properties may offer broader therapeutic benefits by influencing these pathological pathways. It works by inhibiting complexes I and IV of the electron transport chain, which reduces the strain on malfunctioning complex V and decreases the production of harmful free radicals. Additionally, metformin’s impact on mTOR signaling could improve energy metabolism in ME/CFS and LC by downregulating an overactive but underperforming protein, thereby alleviating symptoms. Beyond the impact on cellular metabolism, metformin has shown to have anti-inflammatory, vascular, gastrointestinal, neuroprotective and epigenetic effects.

We explore this impact of metformin and the potential role it could play to help people with ME/CFS. While metformin shows promise, it is unlikely to be a stand-alone solution. Instead, it may be part of a broader treatment strategy that includes other therapies targeting neurocognitive and autonomic impairments.

Source: David Fineberg, Alain Moreau, Elena K. Schneider-Futschik, and Christopher W. Armstrong. A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID. ACS Pharmacology & Translational Science Article ASAP. DOI: 10.1021/acsptsci.5c00229 https://pubs.acs.org/doi/full/10.1021/acsptsci.5c00229 (Full text)

Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC or “long COVID”) and chronic fatigue syndrome/myalgic encephalitis (CFS/ME) share symptoms such as exertional dyspnea. We used exercise oxygen pathway analysis, comprising six parameters of oxygen transport and utilization, to identify limiting mechanisms in both conditions. Invasive cardiopulmonary exercise testing was performed on 15 PASC patients, 11 CFS/ME patients, and 11 controls.

We evaluated the contributions of alveolar ventilation (V̇a), lung diffusion capacity (DL ), cardiac output (Q̇), skeletal muscle diffusion capacity (DM ), hemoglobin (Hb), and mitochondrial oxidative phosphorylation (Vmax) to peak oxygen consumption (V̇O2peak). To simulate targeted interventions, each variable was sequentially normalized to assess its impact on V̇O2peak. V̇O2peak was significantly reduced in both PASC and CFS/ME compared to controls.

Skeletal muscle O2 diffusion (DM ) was the most impaired parameter in both patient groups (p = 0.01). Correcting DM alone improved V̇O2 by 66% in PASC (p = 0.008) and 34.7% in CFS/ME (p = 0.06), suggesting a dominant role for peripheral O2 extraction in exercise limitation. Impaired skeletal muscle oxygen diffusion (DM ) is a shared mechanism of exercise intolerance in PASC and CFS/ME and may represent a therapeutic target. However, our findings are limited by small sample size.

Source: Jothi S, Insel M, Claessen G, Kubba S, Howden EJ, Ruiz-Carmona S, Levine T, Rischard FP. Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation. Physiol Rep. 2025 Sep;13(17):e70535. doi: 10.14814/phy2.70535. PMID: 40892700. https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.70535 (Full text)

Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study

Abstract:

Background and Aims: Increasing evidence suggests that COVID-19 survivors experience long-term cardiovascular complications possibly through development of vascular damage. The study aimed to investigate whether accelerated vascular ageing occurs after COVID-19 infection, and if so, identify its determinants.
Methods: This prospective, multicentric, cohort study, included 34 centres in 16 countries worldwide, in 4 groups of participants—COVID-19-negative controls (ⅰ) and three groups of individuals with recent (6 ± 3 months) exposure to SARS-CoV-2: not hospitalized (ⅱ), hospitalized in general wards (ⅲ), and hospitalized in intensive care units (ⅳ). The main outcome was carotid-femoral pulse wave velocity (PWV), an established biomarker of large artery stiffness.
Results: 2390 individuals (age 50 ± 15 years, 49.2% women) were recruited. After adjustment for confounders, all COVID-19-positive groups showed higher PWV (+0.41, +0.37, and +0.40 m/s for groups 2–4, P < .001, P = .001 and P = .003) vs. controls [PWV 7.53 (7.09; 7.97) m/s adjusted mean (95% CI)]. In sex-stratified analyses, PWV differences were significant in women [PWV (+0.55, +0.60, and +1.09 m/s for groups 2–4, P < .001 for all)], but not in men. Among COVID-19 positive women, persistent symptoms were associated with higher PWV, regardless of disease severity and cardiovascular confounders [adjusted PWV 7.52 (95% CI 7.09; 7.96) vs. 7.13 (95% CI 6.67; 7.59) m/s, P < .001]. A stable or improved PWV after 12 months was found in the COVID+ groups, whereas a progression was observed in the COVID− group.
Conclusions: COVID-19 is associated with early vascular ageing in the long term, especially in women.

Source: Rosa Maria Bruno, Smriti Badhwar, Leila Abid, Mohsen Agharazii, Fabio Anastasio, Jeremy Bellien, Otto Burghuber, Luca Faconti, Jan Filipovsky, Lorenzo Ghiadoni, Cristina Giannattasio, Bernhard Hametner, Alun D Hughes, Ana Jeroncic, Ignatios Ikonomidis, Mai Tone Lonnebakken, Alessandro Maloberti, Christopher C Mayer, Maria Lorenza Muiesan, Anna Paini, Andrie Panayiotou, Chloe Park, Chakravarthi Rajkumar, Carlos Ramos Becerra, Bart Spronck, Dimitrios Terentes-Printzios, Yesim Tuncok, Thomas Weber, Pierre Boutouyrie, the CARTESIAN Investigators , Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study, European Heart Journal, 2025;, ehaf430, https://doi.org/10.1093/eurheartj/ehaf430 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf430/8236450 (Full text)

Mitochondrial function is impaired in long COVID patients

Abstract:

Background: The Long COVID syndrome is a major global health problem, affecting approximately 10–20% of individuals infected with SARS-CoV-2 virus with many remaining symptomatic beyond one year. Fatigue, reduced exercise tolerance and hyperlactataemia on minimal exertion have led to the suggestion of a bioenergetic defect. We hypothesised that mitochondrial dysfunction is a pathological feature in Long COVID cases and would correlate with clinical outcome.

Methods: This prospective, case-controlled, observational study recruited 27 participants with an established diagnosis of Long COVID syndrome from a single tertiary clinic together with 16 age-matched controls aged 25–65 years. Seahorse-based mitochondrial flux analysis and bioenergetics profile of isolated peripheral blood mononuclear cells (PBMCs) was performed and correlated with clinical phenotype.

Findings: Long COVID cases had an increased baseline and ATP-induced oxygen consumption rate with a significant attenuation in tetramethylrhodamine methyl ester perchlorate fluorescence response to oligomycin. Correlations were observed between mitochondrial function and autonomic health, quality of life and time from index infection. Sex-specific differences were also observed.

Interpretation: PBMCs from Long COVID subjects exhibit an exceptional and distinctive change in ATP synthase, as it contributes to the mitochondrial membrane potential rather than using it exclusively to generate ATP. The findings suggest that the enzyme runs both forward and reverse reactions, synthesising and hydrolysing ATP. The correlation of mitochondrial function with clinical phenotype in Long COVID may indicate a causal relationship and warrants further validation in larger scale studies.

Source: Macnaughtan, J., Chau, K. Y., Brennan, E., Toffoli, M., Spinazzola, A., Hillman, T., … Schapira, A. H. V. (2025). Mitochondrial function is impaired in long COVID patients. Annals of Medicine, 57(1). https://doi.org/10.1080/07853890.2025.2528167 https://www.tandfonline.com/doi/full/10.1080/07853890.2025.2528167 (Full text)

ME/CFS and PASC Patient-Derived Immunoglobulin Complexes Disrupt Mitochondrial Function and Alter Inflammatory Marker Secretion

Abstract:

Autoimmunity is a key clinical feature in both post-infectious Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and Post-Acute Sequelae of COVID (PASC). Passive transfer of immunoglobulins from patients’ sera into mice induces some clinical features of PASC. IgG-induced transfer of disease phenotypes has long been appreciated, yet the exact mechanism of disease development remains largely elusive.

Here, we demonstrate that IgG isolated from post-infectious ME/CFS patients selectively induces mitochondrial fragmentation in human endothelial cells, thereby altering mitochondrial energetics. This effect is lost upon cleavage of IgG into its Fab and Fc fragments.

The digested Fab fragment from ME/CFS alone was able to alter the mitochondrial energetics, resembling the effect of intact IgG. In contrast, the Fc fragment alone induced a hypometabolic phenotype characterized by a trend towards reduced overall ATP content. IgG from ME/CFS and PASC patients induced distinct but separate cytokine secretion profiles in healthy PBMCs.

Proteomics analysis of IgG-bound immune complexes revealed significant changes within the immune complexes of ME/CFS patients, affecting extracellular matrix organization, while the same from PASC patients pointed towards alterations in hemostasis and blood clot regulation.

We demonstrate that IgGs from ME/CFS patients carry a chronic protective stress response that promotes mitochondrial adaptation via fragmentation, without altering mitochondrial ATP generation capacity in endothelial cells. Together, these results highlight a potential pathogenic role of IgG in post-infectious ME/CFS and point to novel therapeutic strategies targeting antibody-mediated metabolic dysregulation.

Source: Bhupesh Kumar Prusty, Zheng Liu, Claudia Hollmann, Sharada Kalanidhi, Andreas Schlosser, Stephanie Lammer, Georgy Nikolayshvili, E mils Edgars Basens, Liba Sokolovska, Zaiga Nora-Krukle, Robert K Naviaux, Gabriela Riemekasten, Rebekka Rust, Judith Bellmann, Friedemann Paul, Franziska Sotzny, Carmen Scheibenbogen. ME/CFS and PASC Patient-Derived Immunoglobulin Complexes Disrupt Mitochondrial Function and Alter Inflammatory Marker Secretion. medRxiv 2025.08.06.25332978; doi: https://doi.org/10.1101/2025.08.06.25332978 https://www.medrxiv.org/content/10.1101/2025.08.06.25332978v1 (Full text available as PDF file)

Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome

Abstract:

Patients suffering from chronic fatigue syndrome (CFS) or post-COVID syndrome (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial function and morphology may play a pivotal role. Thus, we aimed to measure the muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity and assess mitochondrial morphology in CFS and PCS patients in comparison to healthy controls (HCs).

Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers using high-resolution respirometry. Mitochondrial morphology (subsarcolemmal/intermyofibrillar mitochondrial form/cristae/diameter/circumference/area) and content (number and proportion/cell) were assessed via electron microscopy. Analyses included differences in OXPHOS between HC, CFS, and PCS, whereas comparisons in morphology/content were made for CFS vs. PCS. OXPHOS capacity of complex I, which was reduced in PCS compared to HC.

While the subsarcolemmal area, volume/cell, diameter, and perimeter were higher in PCS vs. CFS, no difference was observed for these variables in intermyofibrillar mitochondria. Both the intermyofibrillar and subsarcolemmal cristae integrity was higher in PCS compared to CFS. Both CFS and PCS exhibit increased fatigue and impaired mitochondrial function, but the progressed pathological morphological changes in CFS suggest structural changes due to prolonged inactivity or unknown molecular causes. Instead, the significantly lower complex I activity in PCS suggests probably direct virus-induced alterations.

Source: Bizjak DA, Ohmayer B, Buhl JL, Schneider EM, Walther P, Calzia E, Jerg A, Matits L, Steinacker JM. Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome. Int J Mol Sci. 2024 Jan 30;25(3):1675. doi: 10.3390/ijms25031675. PMID: 38338957; PMCID: PMC10855807. https://pmc.ncbi.nlm.nih.gov/articles/PMC10855807/ (Full text)

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

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.

Source: Giménez-Orenga K, Pierquin J, Brunel J, Charvet B, Martín-Martínez E, Lemarinier M, Fried S, Lucas A, Perron H, Oltra E. Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia. Brain Behav Immun Health. 2025 Jul 4;48:101058. doi: 10.1016/j.bbih.2025.101058. PMID: 40726775; PMCID: PMC12302357. https://pmc.ncbi.nlm.nih.gov/articles/PMC12302357/ (Full text)

Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients

Abstract:

Post-viral conditions, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC), share > 95% of their symptoms, but the connection between disturbances in their underlying molecular biology is unclear. This study investigates DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from patients with ME/CFS, LC, and healthy controls (HC).

Reduced Representation Bisulphite Sequencing (RRBS) was applied to the DNA of age- and sex-matched cohorts: ME/CFS (n = 5), LC (n = 5), and HC (n = 5). The global DNA methylomes of the three cohorts were similar and spread equally across all chromosomes, except the sex chromosomes, but there were distinct minor changes in the exons of the disease cohorts towards more hypermethylation.

A principal component analysis (PCA) analysing significant methylation changes (p < 0.05) separated the ME/CFS, LC, and HC cohorts into three distinct clusters. Analysis with a limit of >10% methylation difference and at p < 0.05 identified 214 Differentially Methylated Fragments (DMF) in ME/CFS, and 429 in LC compared to HC. Of these, 118 DMFs were common to both cohorts. Those in promoters and exons were mainly hypermethylated, with a minority hypomethylated. There were rarer examples with either no change in methylation in ME/CFS but a change in LC, or a methylation change in ME/CFS but in the opposite direction in LC. The differential methylation in a number of fragments was significantly greater in the LC cohort than in the ME/CFS cohort.

Our data reveal a generally shared epigenetic makeup between ME/CFS and LC but with specific, distinct changes. Differences between the two cohorts likely reflect the stage of the disease from onset (LC 1 year vs. ME/CFS 12 years), but specific changes imposed by the SARS-CoV-2 virus in the case of the LC patients cannot be discounted. These findings provide a foundation for further studies with larger cohorts at the same disease stage and for functional analyses to establish clinical relevance.

Source: Peppercorn K, Sharma S, Edgar CD, Stockwell PA, Rodger EJ, Chatterjee A, Tate WP. Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients. Int J Mol Sci. 2025 Jul 10;26(14):6631. doi: 10.3390/ijms26146631. PMID: 40724879. https://www.mdpi.com/1422-0067/26/14/6631 (Full text)

Growing recognition of post-acute infection syndromes

Commentary:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID affect large numbers of people, and constitute a substantial burden to the U.S. and global economies. The article by Eckey et al., in this issue of PNAS (1), adds to the growing evidence that the two illnesses have much in common. Moreover, the illnesses may represent just two examples of an even larger, recently recognized class of illness: post-acute infection syndromes (PAIS) (2).
ME/CFS
This illness first attracted attention in the 1980s. Typically, people suffering from ME/CFS previously have been healthy, and then develop a flu-like illness. While that illness appears initially not unlike previous transient illnesses, and while the respiratory symptoms and fever usually improve, people are left with a severe, persisting fatigue, cognitive problems, worsened symptoms following physical or mental exertion or upright posture, as well as unrefreshing sleep, an illness that can last for years (3, 4). The symptoms are not relieved by rest, and greatly impair a person’s ability to function at work and at home. Some individuals are homebound, some largely bedbound. People with ME/CFS often say, in so many words, “I am no longer the person I was.”
In the 1980s, some scientists suspected that a novel human pathogen was causing the illness. Such speculation seemed reasonable, since a novel virus recently had been discovered to cause the AIDS. However, no single, novel pathogen has emerged as the cause of ME/CFS.
Moreover, the standard laboratory tests that were performed in the 1980s generally came back “normal,” leading some to believe there were no underlying biological abnormalities to explain the symptoms. However, over the past 40 y, thousands of studies have identified many underlying abnormalities involving the brain, immune system, energy metabolism, redox imbalance, vascular injury, and gut microbiota (4–9). The symptoms of the illness are, indeed, accompanied by objective abnormalities.
Despite the fact that—in the United States, alone—the illness is estimated to affect up to 3.1 million people, and to generate direct and indirect expenses of approximately $36 to 51 billion annually (3, 10), relatively few investigators have sought to study the illness: the initial skepticism about whether the illness had a biological basis may have created a lingering stigma. That skepticism faded, to some degree, following publication in 2015 of a report from the U.S. National Academies of Science, Engineering and Medicine highlighting the importance of the problem (3).
Long COVID
Then, along came the COVID-19 pandemic. It was predicted that the pandemic would greatly increase the number of people with an ME/CFS-like illness (11), and that has proved to be the case. Many who have “recovered” from acute COVID-19, even from mild cases, have developed a persisting illness (called “long COVID”) with symptoms much like ME/CFS. The cumulative global incidence of long COVID may be as high as 400 million individuals (5, 8), and the costs to the U.S. and global economy (not including the direct costs of healthcare) may be several trillion dollars in the next 5 to 10 y (8, 12).
Comparing ME/CFS and Long COVID
The similarity of the symptoms seen in ME/CFS and long COVID is underscored by the report from Eckey et al. (1). The study involved a survey of nearly 4,000 people with these illnesses. Participants recorded the prevalence and severity of a large number of symptoms, comorbid illnesses, and responses to different treatments.
The authors recognize that such a survey has important limitations. The diagnoses of ME/CFS, long COVID, and comorbid illnesses were self-reported, and not determined by protocol-directed objective testing—although such testing often had been performed by their doctors. Likewise, the responses to different treatments were self-reported, not the results of randomized, placebo-controlled trials. Nevertheless, the large number of study subjects, and the consistency of their responses, suggests that their responses are valid.
Symptoms.
As seen in figure 1 of the report by Eckey et al. (1), the frequency of each of the symptoms is very similar in both illnesses. At the same time, there may be subgroups of people with both ME/CFS and long COVID in whom different symptoms are predominant: it is possible that these subgroups have different underlying pathophysiology, responses to treatments, and prognosis.
Underlying Pathophysiology.
Of course, the fact that the symptoms and symptom frequency are similar does not necessarily mean the two illnesses share an underlying pathophysiology. Nevertheless, it appears that they do. A detailed analysis of the underlying biological abnormalities seen in both illnesses reveals a striking similarity (6).
Comorbid Diseases.
The survey conducted by Eckey et al., addressed two other dimensions by which to compare the two illnesses. First, the survey found that people with the two illnesses frequently had the same comorbid conditions, particularly postural orthostatic tachycardia syndrome (POTS), migraine, dysautonomia, anxiety and depression, mast cell activation syndrome (MCAS), Ehlers–Danlos syndrome (EDS)/joint hypermobility, and attention deficit disorder (ADD) (1).

Response to Therapies.

Patients with the two illnesses also responded similarly to specific treatments. Remarkably, even at the level of specific symptoms, responses were similar in people with the two illnesses, and the drugs most effective against particular symptoms would be expected to improve those symptoms, adding credibility to the self-reported improvement (1). Thus, the study is consistent with others in finding similar symptoms in people with the two illnesses and, additionally, finds similar comorbidities and responses to treatment.

PAIS

ME/CFS and long COVID are not the only two illnesses that share very similar symptoms. Over the past century, there have been many reports of an illness with very similar symptoms following multiple different acute bacterial, viral, fungal, and protozoal infections; hence, the proposal to call all of these illnesses PAIS (2). Long COVID surely is a PAIS (since the inciting infectious agent is known), and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) likely often is (even though the inciting agents often have not been pursued by physicians).

IACIs
PAIS, in turn, are one example of an even larger umbrella category, a group of disorders called IACIs (9, 13). As shown in Fig. 1, we distinguish three categories of IACIs: new organ injury from an infectious agent, such as the development of multiple sclerosis following primary infection with Epstein–Barr virus or duodenal ulcers caused by Helicobacter pylori; accelerated incidence of disease processes that had not yet become apparent before the time of an acute infection (including accelerated atherosclerosis and neurodegeneration post-COVID) (8, 14); and PAIS. Some observers use the term long COVID to include all three categories of illness following acute infection with SARS-CoV-2. We restrict the use of the term long COVID to just the PAIS that can follow SARS-CoV-2 infection.
Read the rest of this article here: https://www.pnas.org/doi/10.1073/pnas.2513877122
Source: A.L. Komaroff, Growing recognition of post-acute infection syndromes, Proc. Natl. Acad. Sci. U.S.A. 122 (29) e2513877122, https://doi.org/10.1073/pnas.2513877122 (2025). https://www.pnas.org/doi/10.1073/pnas.2513877122 (Full text)

Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review

Abstract:

Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis.

In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.

Source: Paroli M, Gioia C, Accapezzato D, Caccavale R. Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review. Int J Mol Sci. 2024 May 29;25(11):5922. doi: 10.3390/ijms25115922. PMID: 38892110; PMCID: PMC11172859. https://pmc.ncbi.nlm.nih.gov/articles/PMC11172859/ (Full text)