Tag: women

Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis

Abstract:

Myalgic Encephalomyelitis (ME) is a complex, multisystem disorder with poorly understood pathophysiological mechanisms. SMPDL3B, a membrane-associated protein expressed in renal podocytes, is essential for lipid raft integrity and glomerular barrier function. We hypothesize that reduced membrane-bound SMPDL3B may contribute to podocyte dysfunction and impaired renal physiology in ME. To investigate this, we quantified soluble SMPDL3B in plasma and urine as a surrogate marker of membrane-bound SMPDL3B status and assessed renal clearance and plasma metabolomic profiles.
In a cross-sectional study of 56 ME patients and 16 matched healthy controls, ME patients exhibited significantly lower urine-to-plasma ratios of soluble SMPDL3B and reduced renal clearance, suggesting podocyte-related abnormalities. Plasma metabolomics revealed dysregulation of metabolites associated with renal impairment, including succinic acid, benzoic acid, phenyllactic acid, 1,5-anhydroglucitol, histidine, and citrate.
In ME patients, plasma SMPDL3B levels inversely correlated with 1,5-anhydroglucitol concentrations and renal clearance. Multivariable modeling identified the urine-to-plasma SMPDL3B ratio as an independent predictor of clearance. Female ME patients showed more pronounced SMPDL3B alterations, reduced clearance, and greater symptom severity. Non-linear associations between soluble SMPDL3B and lipid species further suggest systemic metabolic remodeling.
These findings support soluble SMPDL3B as a potential non-invasive biomarker of renal-podocyte involvement in ME, highlighting sex-specific differences that may inform future therapeutic strategies.
Source: Rostami-Afshari B, Elremaly W, McGregor NR, Huang KJK, Armstrong CW, Franco A, Godbout C, Elbakry M, Abdelli R, Moreau A. Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis. International Journal of Molecular Sciences. 2025; 26(18):8882. https://doi.org/10.3390/ijms26188882 https://www.mdpi.com/1422-0067/26/18/8882 (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)

SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis

Abstract:

Background: Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is emerging as a potential biomarker and therapeutic target in myalgic encephalomyelitis (ME), a complex multisystem disorder characterized by immune dysfunction, metabolic disturbances, and persistent fatigue. This study investigates the role of SMPDL3B in ME pathophysiology and explores its clinical relevance.

Methods: A case-control study was conducted in two independent cohorts: a Canadian cohort (249 ME patients, 63 controls) and a Norwegian replication cohort (141 ME patients). Plasma and membrane-bound SMPDL3B levels were quantified using ELISA and flow cytometry. Gene expression of SMPDL3B and PLCXD1, encoding phosphatidylinositol-specific phospholipase C (PI-PLC), was analyzed by qPCR. The effects of dipeptidyl peptidase-4 (DPP-4) inhibitors-vildagliptin, saxagliptin, and linagliptin-on modulation of membrane-bound and soluble SMPDL3B were assessed in vitro by qPCR, flow cytometry and ELISA.

Results: ME patients exhibited significantly elevated plasma SMPDL3B levels, which correlated with symptom severity. Flow cytometry revealed a reduction in membrane-bound SMPDL3B in monocytes, accompanied by increased PLCXD1 expression and elevated plasma levels of PI-PLC and SMPDL3B. These findings suggest that immune dysregulation in ME may be linked to enhanced cleavage of membrane-bound SMPDL3B by PI-PLC. Sex-specific differences were observed, with female ME patients displaying higher plasma SMPDL3B levels, an effect influenced by estrogen. In vitro, estradiol upregulated SMPDL3B expression, indicating hormonal regulation. Vildagliptin and saxagliptin were tested for their potential to inhibit PI-PLC activity independently of their role as DPP-4 inhibitors, and restored membrane-bound SMPDL3B while reduced its soluble form.

Conclusions: SMPDL3B emerges as a key biomarker for ME severity and immune dysregulation, with its activity influenced by hormonal and PI-PLC regulation. The ability of vildagliptin and saxagliptin to preserve membrane-bound SMPDL3B and reduce its soluble form via PI-PLC inhibition suggests a novel therapeutic strategy. These findings warrant clinical trials to evaluate their potential in mitigating immune dysfunction and symptom burden in ME.

Note: See Correction: SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis

Source: Rostami-Afshari B, Elremaly W, Franco A, Elbakry M, Akoume MY, Boufaied I, Moezzi A, Leveau C, Rompré P, Godbout C, Mella O, Fluge Ø, Moreau A. SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis. J Transl Med. 2025 Jul 7;23(1):748. doi: 10.1186/s12967-025-06829-0. PMID: 40624584; PMCID: PMC12236014. https://pmc.ncbi.nlm.nih.gov/articles/PMC12236014/ (Full text)

Medication use and symptomology in North American women with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: There are no known curative treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and current therapeutic regimens often yield inconsistent results. Despite the profound physical and mental burden experienced by those living with ME/CFS, patients often face a trial-and-error process in finding medications that offer some relief.

Method: The current study surveyed 135 North American women diagnosed with ME/CFS to characterize medication use in relation to disease features, symptomology, and function. Medications were classified into 9 categories according to their primary mechanism of action and therapeutic use.

Results: Participants were primarily middle-aged (47.1 ± 15.3 years) and were diagnosed for a mean duration of 8.4 ± 9.5 years (mean ± SD). Responses showed 68.6% of participants reported taking medications specifically for ME/CFS. Of those taking ME/CFS-related symptom medications, the average use was 3.0 medications per patient, with higher use in US compared to Canadian participants. Analgesic medications (31.7%) were the most frequently used, followed by psychotropic (26.4%), and immune-related medications (10.6%). These trends persisted across different symptom profiles, apart from gastrointestinal associated medication use replacing immune-related medications in those with gastrointestinal, neurological, and psychiatric symptoms. There was no significant correlation found between the number of medications used with disease duration, age, or age at diagnosis. However, a U-shaped relationship between ME/CFS-related symptom medication use and functional capacity as assessed by self-reported physical movement (hours/week) was evident.

Conclusion: Our study highlights the diverse and complex patterns in pharmacological treatment regimens for ME/CFS in women, while also underscoring the need for more tailored and evidence-based therapeutic strategies to address the varied symptom profiles.

Source: Pochakom A, MacNevin G, Madden RF, Moss AC, Martin JM, Lalonde-Bester S, Parnell JA, Stein E, Shearer J. Medication use and symptomology in North American women with myalgic encephalomyelitis/chronic fatigue syndrome. Front Med (Lausanne). 2025 Jun 6;12:1543158. doi: 10.3389/fmed.2025.1543158. PMID: 40547918; PMCID: PMC12179203. https://pmc.ncbi.nlm.nih.gov/articles/PMC12179203/ (Full text)

Long-term neurological and cognitive impact of COVID-19: a systematic review and meta-analysis in over 4 million patients

Abstract:

Background: Neuropsychiatric symptoms emerged early in the COVID-19 pandemic as a key feature of the virus, with research confirming a range of neuropsychiatric manifestations linked to acute SARS-CoV-2 infection. However, the persistence of neurological symptoms in the post-acute and chronic phases remains unclear. This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning.

Methods: A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, EBSCO, and CENTRAL, up to March 22, 2024. Studies evaluating the prevalence of long-term neurological symptoms in COVID-19 survivors with at least six months of follow-up were included. Pooled prevalence estimates, subgroup analyses, and meta-regression were performed, and publication bias was assessed.

Results: The prevalence rates for the different symptoms were as follows: fatigue 43.3% (95% CI [36.1-50.9%]), memory disorders 27.8% (95% CI [20.1-37.1%]), cognitive impairment 27.1% (95% CI [20.4-34.9%]), sleep disorders 24.4% (95% CI [18.1-32.1%]), concentration impairment 23.8% (95% CI [17.2-31.9%]), headache 20.3% (95% CI [15-26.9%]), dizziness 16% (95% CI [9.5-25.7%]), stress 15.9% (95% CI [10.2-24%]), depression 14.0% (95% CI [10.1-19.2%]), anxiety 13.2% (95% CI [9.6-17.9%]), and migraine 13% (95% CI [2.2-49.8%]). Significant heterogeneity was observed across all symptoms. Meta-regression analysis showed higher stress, fatigue, and headache in females, and increased stress and concentration impairment with higher BMI.

Conclusions: Neurological symptoms are common and persistent in COVID-19 survivors. This meta-analysis highlights the significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery.

Source: Elboraay T, Ebada MA, Elsayed M, Aboeldahab HA, Salamah HM, Rageh O, Elmallahy M, AboElfarh HE, Mansour LS, Nabil Y, Eltawab AKA, Atwan H, Alkanj S. Long-term neurological and cognitive impact of COVID-19: a systematic review and meta-analysis in over 4 million patients. BMC Neurol. 2025 Jun 14;25(1):250. doi: 10.1186/s12883-025-04174-9. PMID: 40514644; PMCID: PMC12166599. https://pmc.ncbi.nlm.nih.gov/articles/PMC12166599/ (Full text)

Cognitive Impairments in Two Samples of Individuals with ME/CFS and Long COVID: A Comparative Analysis

Abstract:

Cognitive impairments, including memory and concentration difficulties, are common in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. These conditions frequently co-occur, but it remains unclear how cognitive difficulties differ between individuals with ME/CFS, long COVID, both, or neither. The purpose of this study was to examine cognitive impairment presence and type for individuals with and without these conditions.

Data from the 2022 and 2023 National Health Interview Survey were analyzed. Participants included 27,512 and 29,404 U.S. adults in 2022 and 2023, respectively. Survey weights and variance estimation variables were utilized and multivariate logistic regression models assessed the likelihood of cognitive difficulty, accounting for sociodemographics and shared variance. Participants from both cohorts were primarily female, white, and non-Hispanic/Latine, with an average age of 48.1 years in both cohorts.

ME/CFS (aOR 6.18; 95% CI 4.82-7.93; aOR 5.33; 95% CI 4.04-7.05) and long COVID (aOR 2.01; 95% CI 1.67-2.44; aOR 2.16; 95% CI 1.82-2.56) were significantly associated with reported cognitive difficulties, after controlling for the other condition and sociodemographic factors. Individuals with ME/CFS, particularly those with comorbid long COVID, are especially prone to memory and concentration difficulties.

Source: Sirotiak Z, Adamowicz JL, Thomas EBK. Cognitive Impairments in Two Samples of Individuals with ME/CFS and Long COVID: A Comparative Analysis. J Clin Psychol Med Settings. 2025 Mar 22. doi: 10.1007/s10880-025-10074-4. Epub ahead of print. PMID: 40120036. https://pubmed.ncbi.nlm.nih.gov/40120036/

Digital health app data reveals an effect of ovarian hormones on long COVID and myalgic encephalomyelitis symptoms

Abstract:

Background. Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) disproportionately affect females, suggesting modulation by sex hormones. We sought to investigate whether symptom severity is influenced by changes in sex hormones over the menstrual cycle, or by hormonal contraception.

Methods: We carried out a retrospective analysis of menstrual and symptom data, prospectively collected via the Visible app from individuals with long COVID, ME/CFS, or both, who had regular menstrual cycles, between 7 September 2022 and 6 March 2024. Mixed-effects models were used to examine associations between symptom severity, menstrual cycle phase and contraception type.

Findings: 948 users were included; 100% of users were female and 92.6% identified as women. The most tracked symptoms were fatigue (99.5% of users), brain fog (88.3%), headaches (85.1%) and muscle aches (78.6%). All menstrual cycle phases showed a modest, but significant, improvement compare to the menstrual phase, most markedly in the early luteal (IRR 0.963%, 95% CI: 0.958 – 0.968), but also the follicular (IRR = 0.985, 95% CI: 0.981 – 0.990) and late luteal phase (IRR = 0.980, 95% CI: 0.974-0.985). Crashes (sudden and severe worsening of symptoms following exertion) were significantly more frequent during menstruation than in other phases. Users of combined hormonal contraception (n=70) had a statistically significant reduction in overall symptom score (OR = 0.827, 95% CI: 0.690 – 0.992) and crash incidence (OR = 0.548, 95% CI: 0.350 – 0.856) compared to those not using hormonal contraception (=786).

Interpretation: Menstruation is associated with worsened symptoms in long COVID and ME/CFS. Users of combined hormonal contraception report a lower symptom burden than non-users, suggesting a modulatory role of ovarian hormones. These findings could empower menstruating people living with long COVID and ME/CFS to anticipate cyclical changes in symptoms and plan their activities accordingly, and could also inform their use of contraception.

Source: Abigail Goodship, Rory Preston, Joseph T Hicks, Harry Leeming, Christian Morgenstern, Victoria Male. Digital health app data reveals an effect of ovarian hormones on long COVID and myalgic encephalomyelitis symptoms. medRxiv 2025.01.24.25321092; doi: https://doi.org/10.1101/2025.01.24.25321092 https://www.medrxiv.org/content/10.1101/2025.01.24.25321092v1 (Full text available as PDF file)

Association Between Chronic Pain and Fatigue Severity with Weather and Air Pollution Among Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Weather and air quality conditions have been anecdotally reported to be related to symptom fluctuations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), but this has never been empirically investigated. This exploratory study aims to examine the effects of weather and air quality on daily fluctuations of chronic pain and fatigue in women with ME/CFS. In an intensive longitudinal design, 58 participants with ME/CFS provided daily pain and fatigue ratings for an average of 61 days.

Daily weather and air quality data were obtained from the National Oceanic and Atmospheric Administration and the US Environmental Protection Agency for the Birmingham, AL area. Linear mixed models revealed a significant relationship between days with more severe pain and worse Air Quality Indices (AQI, p < 0.001), lower wind speeds (p = 0.009), greater particulate matter (p = 0.037), and lower carbon monoxide (p = 0.004), sulfur dioxide (p = 0.003), and ozone levels (p = 0.015).

Greater fatigue was associated with more particulates (p = 0.023) and lower barometric pressure (p = 0.048). These results suggest that air quality and weather can have small effects on ME/CFS symptom severity.

Source: Jones CL, Haskin O, Younger JW. Association Between Chronic Pain and Fatigue Severity with Weather and Air Pollution Among Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Environ Res Public Health. 2024 Nov 26;21(12):1560. doi: 10.3390/ijerph21121560. PMID: 39767402. https://www.mdpi.com/1660-4601/21/12/1560 (Full text)

Overlapping conditions in Long COVID at a multisite academic center

Abstract:

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.

Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.

Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%).

Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.

Source: Grach SL, Dudenkov DV, Pollack B, Fairweather D, Aakre CA, Munipalli B, Croghan IT, Mueller MR, Overgaard JD, Bruno KA, Collins NM, Li Z, Hurt RT, Tal MC, Ganesh R, Knight DTR. Overlapping conditions in Long COVID at a multisite academic center. Front Neurol. 2024 Oct 25;15:1482917. doi: 10.3389/fneur.2024.1482917. PMID: 39524912; PMCID: PMC11543549. https://pmc.ncbi.nlm.nih.gov/articles/PMC11543549/ (Full text)

Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study

Abstract:

Background: Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity.

Methods: We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented.

Results: 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen’s d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident.

Conclusions: More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS.

Source: Fall EA, Chen Y, Lin JS, Issa A, Brimmer DJ, Bateman L, Lapp CW, Podell RN, Natelson BH, Kogelnik AM, Klimas NG, Peterson DL, Unger ER; MCAM Study Group. Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study. BMC Neurol. 2024 Oct 18;24(1):399. doi: 10.1186/s12883-024-03872-0. PMID: 39425035; PMCID: PMC11488184. https://pmc.ncbi.nlm.nih.gov/articles/PMC11488184/ (Full text)