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)

A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation

Abstract:

Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological disorder characterized by post-exertional malaise. Despite its clinical relevance, the disease mechanisms of ME/CFS are not fully understood. The previous studies targeting brain function or metabolites have been inconclusive in understanding ME/CFS complexity. We combined single-voxel magnetic resonance spectroscopy (SV-MRS) and functional magnetic resonance imaging (fMRI). Our objectives were to examine the feasibility of the multimodal MRI protocol, identify possible differences between ME/CFS and healthy controls (HCs), and relate MRI findings with clinical symptoms.

Methods: We enrolled 18 female ME/CFS participants (mean age: 39.7 ± 12.0 years) and five HCs (mean age: 45.6 ± 14.5 years). SV-MRS spectra were acquired from three voxels of interest: the anterior cingulate gyrus (ACC), brainstem (BS), and left dorsolateral prefrontal cortex (L-DLPFC). Whole-brain fMRI used n-back task testing working memory and executive function. The feasibility was assessed as protocol completion rate and time. Group differences in brain metabolites and fMRI activation between ME/CFS and HCs were compared and correlated with behavioral and symptom severity measurements.

Results: The completion rate was 100% regardless of participant group without causing immediate fatigue. ME/CFS appeared to show a higher N-Acetylaspartate in L-DLPFC compared to HCs (OR = 8.49, p = 0.040), correlating with poorer fatigue, pain, and sleep quality scores (p‘s = 0.001-0.015). An increase in brain activation involving the frontal lobe and the brainstem was observed in ME/CFS compared to HCs (Z > 3.4, p‘s < 0.010).

Conclusions: The study demonstrates the feasibility of combining MRS and fMRI to capture neurochemical and neurophysiological features of ME/CFS in female participants. Further research with larger cohorts of more representative sampling and follow-ups is needed to validate these apparent differences between ME/CFS and HCs.

Source: Kaur R, Greeley B, Ciok A, Mehta K, Tsai M, Robertson H, Debelic K, Zhang LX, Nelson T, Boulter T, Siu W, Nacul L, Song X. A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation. Medicina (Kaunas). 2024 Aug 22;60(8):1370. doi: 10.3390/medicina60081370. PMID: 39202651. https://www.mdpi.com/1648-9144/60/8/1370 (Full text)

Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment

Abstract:

Objective: To report the prevalence and severity of nonpelvic symptoms for patients with venous-origin chronic pelvic pain (VO-CPP) and to describe outcomes after pelvic vein stenting and embolization.

Methods: We retrospectively reviewed outcomes of 45 women with VO-CPP who underwent treatment with iliac vein stenting and/or embolization. Patients completed symptom-severity questionnaires before and after treatment that assessed for pelvic pain, and multiple other symptoms, including brain fog, anxiety, depression, musculoskeletal pain, fatigue, migraines and more.

Results: Patient age ranged from 18 to 65 years. The prevalence of common symptoms was as follows: migraines, 69%; brain fog, 76%; anxiety attacks, 58%; excess sweating, 64%; hip pain, 73%; diarrhea, 62%; constipation, 76%; and abdominal bloating, 82%. After treatment, most symptom scores improved by more than 50%; exceptions were excessive sweating (41% improvement) and bloating (47% improvement). Prevalence of individual symptoms that bundle into POTS ranged from 29% to 76%, where symptom improvement ranged from 23% to 59% after treatment. Overlapping individual symptoms characteristic of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) were present in 64% to 82% of patients and all improved by 49% to 63% after treatment.

Conclusions: Pelvic venous flow abnormality is linked causally to a spectrum of interrelated symptoms, of which many can be bundled into named syndromes of unknown cause. With catheter- based treatment of pelvic venous pooling, nonpelvic symptom and syndrome scores improved.

Source: Smith SJ, Smith BH, Sichlau MJ, Chen B, Knight D, Rowe PC. Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment. Phlebology. 2024 Aug 10:2683555241273109. doi: 10.1177/02683555241273109. Epub ahead of print. PMID: 39126670.  https://pubmed.ncbi.nlm.nih.gov/39126670/

‘The world was going through what we go through everyday’: The experiences of women with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) living with their partners during the COVID-19 lockdown in the United Kingdom

Abstract:

Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term debilitating illness characterised by profound and persistent fatigue (JAMA: The Journal of the American Medical Association, 313, 2015, 1101). The current study aims to explore the experiences of women with ME/CFS living with their partners during the COVID-19 pandemic in the United Kingdom.

Design: The study adopted a qualitative design comprising semi-structured interviews with participants. Interviews were analysed using thematic analysis (TA).

Methods: Participants were women with ME/CFS (n = 21) recruited through ME/CFS support groups in the United Kingdom. All participants were in romantic relationships and lived with their partners.

Results: Data were organised into three themes: (1) lockdown disrupting routine, (2) reducing difference and (3) fear of getting COVID-19. People with ME/CFS found that lockdown disrupted their well-established routines. Although routines were disrupted by partners and increased working-from-home practices, participants found having partners at home helpful. People with ME/CFS believed that the changes induced by the pandemic reduced the differences between themselves and the outside world which, prior to lockdown, had felt prominent. They were fearful of getting COVID-19 as they believed this would make their ME/CFS worse. This meant that for people with ME/CFS, the lifting of the lockdown restrictions was an anxiety-provoking time, hence impacting symptoms. People with ME/CFS continued to adhere to government guidelines after national restrictions were eased.

Conclusions: This study outlines the experiences of women with ME/CFS during COVID-19, alongside the long-term impact this has had due to the changes that the pandemic imposed. These findings may have implications for those with long COVID.

Source: Sehmbi T, Wearden A, Peters S, Dienes K. ‘The world was going through what we go through everyday’: The experiences of women with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) living with their partners during the COVID-19 lockdown in the United Kingdom. Br J Health Psychol. 2024 Mar 6. doi: 10.1111/bjhp.12717. Epub ahead of print. PMID: 38448223. https://bpspsychub.onlinelibrary.wiley.com/doi/10.1111/bjhp.12717 (Full text)

The impact of “long COVID” on menstruation in Chinese female college students and the intervention of acupuncture

Abstract:

This study aimed to explore the potential application value of acupuncture in alleviating the impact of long COVID on women’s menstrual cycles, by investigating the occurrence of long COVID among female college students, its effects on menstruation, and the intervention of acupuncture. This cross-sectional study surveyed female college students with a history of coronavirus disease 2019 (COVID-19) before April 10, 2023.

A questionnaire was used to analyze demographic characteristics, post-COVID sequelaes, duration of symptoms, and treatments received during that period. Among the 731 participants enrolled in the survey, 468 were female undergraduate students who met the analysis criteria. Among them, 85 individuals fit the definition of “Long COVID” (18.16%).

Within the group of patients with long COVID, 69 individuals experienced changes in their overall menstrual patterns compared to the 6 months prior to contracting the novel coronavirus (81.18%). Additionally, 17 individuals opted for acupuncture treatment following the onset of COVID-19 (20.00%), which resulted in less impact on their menstrual cycle (41.18% vs 64.71% without receiving acupuncture, OR = 2.62), menstrual period duration (41.18% vs 64.71%, OR = 2.62), menstrual flow (47.06% vs 69.18%, OR = 2.52), and the color of menstrual blood (41.18% vs 63.24%, OR = 2.46) among these patients. Long COVID had a certain impact on menstruation.

Acupuncture potentially alleviates the clinical symptoms of long COVID and reduces its impact on women’s menstrual cycle, thus having potential therapeutic value in the treatment of long COVID.

Source: Dong J, Ni J, Zhang Z, Yan H, Xu J, Zhao J. The impact of “long COVID” on menstruation in Chinese female college students and the intervention of acupuncture. Medicine (Baltimore). 2024 Feb 9;103(6):e36818. doi: 10.1097/MD.0000000000036818. PMID: 38335408; PMCID: PMC10860984. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860984/ (Full text)

High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study

Abstract:

The long-term effects of SARS-CoV-2 infection represent a relevant global health problem. Long COVID (LC) is defined as a complex of signs and symptoms developed during or after SARS-CoV-2 infection and lasting > 12 weeks. In common variable immunodeficiency (CVID) patients, we previously reported higher risk of hospitalization and death during SARS-CoV-2 infection, as well as prolonged swab positivity and frequent reinfections.

The aim of the present study was to assess the risk of LC in an Italian cohort of CVID patients. We used a translated version of the survey proposed by Centers for Disease Control and Prevention (CDC) to collect data on LC. In the enrolled cohort of 175 CVID patients, we found a high prevalence of LC (65.7%). The most frequent LC symptoms were fatigue (75.7%), arthralgia/myalgia (48.7%), and dyspnea (41.7%). The majority of patients (60%) experienced prolonged symptoms, for at least 6 months after infection.

In a multivariate analysis, the presence of complicated phenotype (OR 2.44, 95% CI 1.88-5.03; p = 0.015), obesity (OR 11.17, 95% CI 1.37-90.95; p = 0.024), and female sex (OR 2.06, 95% CI 1.09-3.89; p = 0.024) significantly correlated with the development of LC.

In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients could optimize management of this new and alarming complication of SARS-CoV-2 infection.

Source: Villa A, Milito C, Deiana CM, Gambier RF, Punziano A, Buso H, Bez P, Lagnese G, Garzi G, Costanzo G, Giannuzzi G, Pagnozzi C, Dalm VASH, Spadaro G, Rattazzi M, Cinetto F, Firinu D. High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study. J Clin Immunol. 2024 Feb 6;44(2):59. doi: 10.1007/s10875-024-01656-2. PMID: 38319477; PMCID: PMC10847195. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847195/ (Full text)