Category: Overlapping Illnesses

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/

Post-Exertional Malaise in Veterans with Gulf War Illness

Abstract:

Post-exertional malaise (PEM) is a potentially debilitating aspect of Gulf War Illness (GWI) that has received limited research attention. The purpose of the present investigation was to determine symptom severity changes following exercise in Veterans with GWI compared to control Veterans without GWI (CO).

Sixty-seven Veterans (n=39 GWI; n=28 CO) underwent a 30-minute submaximal exercise challenge at 70% of heart rate reserve. Symptom measurements (e.g. fatigue, pain) occurred pre-, immediately post-, and 24-hours post-exercise. Self-reported physical and mental health, and physiological and perceptual responses to exercise were compared between groups using descriptive statistics, independent samples t-tests and repeated measures Analysis of Variance (RM-ANOVA).

Post-exertional malaise was modeled using Group by Time (2 × 3) doubly-multivariate, RM-MANOVAs for (1) mood, (2) pain and (3) GWI-related symptoms, respectively (α=0.05). Data were analyzed for the full sample of Veterans with GWI (n=39) compared to CO (n=28) and a subsample of Veterans (n=18) who endorsed “feeling unwell after physical exercise or exertion” (“PEM endorsers”) during screening.

Veterans with GWI reported significantly lower physical and mental health. Groups exercised at similar relative exercise intensities, but GWI perceived exercise as more painful and fatiguing. Group-by-Time interactions were not significant for the entire sample for the three PEM models, however limiting the GWI sample to “PEM endorsers” resulted in significant interactions for Pain- and GWI-related PEM models.

These results indicate that not all GVs with GWI experience PEM 24 hr after exercise, and that more research is needed to determine the extent that exercise worsens symptoms in GWI.

Source: Lindheimer JB, Stegner AJ, Wylie GR, Klein-Adams JC, Almassi NE, Ninneman JV, Van Riper SM, Dougherty RJ, Falvo MJ, Cook DB. Post-exertional malaise in veterans with gulf war illness. Int J Psychophysiol. 2020 Jan;147:202-212. doi: 10.1016/j.ijpsycho.2019.11.008. Epub 2019 Nov 28. PMID: 31786249; PMCID: PMC6957714. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957714/ (Full text)

Developing a clinical-pathological framework of long COVID-related fatigue applied to public safety workers

Abstract:

In the wake of the COVID-19 pandemic, millions worldwide are still struggling with persistent or recurring symptoms known as long COVID. Fatigue is one of the most prevalent symptoms associated with long COVID, and for many it can be debilitating. Understanding the potential pathological processes that link fatigue to long COVID is critical to better guide treatment. Challenges with diagnosis and treatment are reviewed, recognizing that post-COVID fatigue does not always present with corroborating clinical evidence, a situation that is frustrating for both patients and healthcare providers.

Firefighters are a group of public safety workers who are particularly impacted by long COVID-related fatigue. Firefighters must be able to engage in strenuous physical activity and deal with demanding psychological situations, both of which may be difficult for those suffering from fatigue. Disruption in public safety worker health can potentially impact community welfare. This review creates a framework to explain the clinical-pathological features of fatigue resulting from long COVID, addresses diagnosis and treatment challenges, and explores the unique impact fatigue may pose for public safety workers and their organizations.

Source: Lofrano-Porto A, D’Isabel S, Smith DL. Developing a clinical-pathological framework of long COVID-related fatigue applied to public safety workers. Front Med (Lausanne). 2024 Jul 17;11:1387499. doi: 10.3389/fmed.2024.1387499. PMID: 39086937; PMCID: PMC11288841. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288841/ (Full text)

Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS)

Abstract:

Post-acute COVID-19 vaccination syndrome (PACVS) is a chronic disease triggered by SARS-CoV-2 vaccination (estimated prevalence 0.02%). PACVS is discriminated from the normal post-vaccination state by altered receptor antibodies, most notably angiotensin II type 1 and alpha-2B adrenergic receptor antibodies. Here, we investigate the clinical phenotype using a study registry encompassing 191 PACVS-affected persons (159 females/32 males; median ages: 39/42 years).

Unbiased clustering (modified Jaccard index) of reported symptoms revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (>80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, and vasomotor dysfunction; (ii) cardiovascular impairment; and (iii) cognitive impairment, headache, and visual and acoustic dysfunctions were also frequently represented.

Notable abnormalities of standard serum markers encompassing increased interleukins 6 and 8 (>80%), low free tri-iodine thyroxine (>80%), IgG subclass imbalances (>50%), impaired iron storage (>50%), and increased soluble neurofilament light chains (>30%) were not associated with specific symptoms.

Based on these data, 131/191 participants fit myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and simultaneously also several other established dysautonomia syndromes. Furthermore, 31/191 participants fit none of these syndromes. In conclusion, PACVS could either be an outlier of ME/CFS or a dysautonomia syndrome sui generis.

Source: Mundorf AK, Semmler A, Heidecke H, Schott M, Steffen F, Bittner S, Lackner KJ, Schulze-Bosse K, Pawlitzki M, Meuth SG, Klawonn F, Ruhrländer J, Boege F. Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS). Vaccines (Basel). 2024 Jul 18;12(7):790. doi: 10.3390/vaccines12070790. PMID: 39066428; PMCID: PMC11281408. Mundorf AK, Semmler A, Heidecke H, Schott M, Steffen F, Bittner S, Lackner KJ, Schulze-Bosse K, Pawlitzki M, Meuth SG, Klawonn F, Ruhrländer J, Boege F. Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS). Vaccines (Basel). 2024 Jul 18;12(7):790. doi: 10.3390/vaccines12070790. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281408/ (Full text)

Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses

Abstract:

(1) Background: Macrophagic myofasciitis (MMF) is an inflammatory histopathological lesion demonstrating long-term biopersistence of vaccine-derived aluminum adjuvants within muscular phagocytic cells. Affected patients suffer from widespread myalgia and severe fatigue consistent with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a poorly understood disorder suspected to result from chronic immune stimulation by infectious and inorganic particles.

(2) Methods: In this study we determined the immuno-metabolic properties of MMF phagocytic cells compared to controls, at rest and upon exposure to aluminum oxyhydroxide adjuvant, with or without adsorbed antigens, using protein quantification and an oxygen consumption assay.

(3) Results: MMF and control cells similarly internalized the adjuvant and vaccine but MMF cells specifically expressed Rubicon and Nox2, two molecules unique to the LC3-associated phagocytosis (LAP) machinery, a non-canonical autophagic pathway able to downregulate canonical autophagy. MMF cells exhibited an altered inflammatory secretome, producing more pain-inducing CXC chemokines and less TNF-α than controls, consistent with chronic myalgia and exhaustion of the immune system previously documented in ME/CFS. MMF cells exhibited mitochondrial metabolism dysfunction, with exacerbated reaction to adjuvanted vaccine, contrasting with limited spare respiratory capacity and marked proton leak weakening energy production.

(4) Conclusions: MMF phagocytes seemingly use LAP to handle aluminum oxyhydroxide vaccine particles, secrete pain-inducing molecules, and exhibit exacerbated metabolic reaction to the vaccine with limited capacity to respond to ongoing energetic requests.

Source: Masson JD, Badran G, Gherardi RK, Authier FJ, Crépeaux G. Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses. Toxics. 2024 Jul 4;12(7):491. doi: 10.3390/toxics12070491. PMID: 39058143. https://www.mdpi.com/2305-6304/12/7/491 (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection

Abstract:

Importance: Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective: To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection-like index illness.

Design, setting, and participants: This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 years with acute symptoms suggestive of SARS-CoV-2 infection who received a US Food and Drug Administration-approved SARS-CoV-2 test at the time of illness and did not die or withdraw from the study by 3 months. Follow-up surveys were collected through February 28, 2023.

Exposure: COVID-19 status (positive vs negative) at enrollment.

Main outcome and measures: The main outcome was the weighted proportion of participants with ME/CFS-like illness based on the 2015 Institute of Medicine clinical case definition using self-reported symptoms.

Results: A total of 4378 participants were included in the study. Most were female (3226 [68.1%]). Mean (SD) age was 37.8 (11.8) years. The survey completion rates ranged from 38.7% (3613 of 4738 participants) to 76.3% (1835 of 4738) and decreased over time. The weighted proportion of participants identified with ME/CFS-like illness did not change significantly at 3 through 12 months of follow-up and was similar in the COVID-19-positive (range, 2.8%-3.7%) and COVID-19-negative (range, 3.1%-4.5%) groups. Adjusted analyses revealed no significant difference in the odds of ME/CFS-like illness at any time point between COVID-19-positive and COVID-19-negative individuals (marginal odds ratio range, 0.84 [95% CI, 0.42-1.67] to 1.18 [95% CI, 0.55-2.51]).

Conclusions and relevance: In this prospective cohort study, there was no evidence that the proportion of participants with ME/CFS-like illness differed between those infected with SARS-CoV-2 vs those without SARS-CoV-2 infection up to 12 months after infection. A 3% to 4% prevalence of ME/CFS-like illness after an acute infection-like index illness would impose a high societal burden given the millions of persons infected with SARS-CoV-2.

Source: Unger ER, Lin JS, Wisk LE, Yu H, L’Hommedieu M, Lavretsky H, Montoy JCC, Gottlieb MA, Rising KL, Gentile NL, Santangelo M, Venkatesh AK, Rodriguez RM, Hill MJ, Geyer RE, Kean ER, Saydah S, McDonald SA, Huebinger R, Idris AH, Dorney J, Hota B, Spatz ES, Stephens KA, Weinstein RA, Elmore JG; Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) Group. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection. JAMA Netw Open. 2024 Jul 1;7(7):e2423555. doi: 10.1001/jamanetworkopen.2024.23555. PMID: 39046739; PMCID: PMC11270135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270135/ (Full text)

Brain microstructural changes and fatigue after COVID-19

Abstract:

Background: Fatigue and cognitive complaints are the most frequent persistent symptoms in patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess fatigue and neuropsychological performance and investigate changes in the thickness and volume of gray matter (GM) and microstructural abnormalities in the white matter (WM) in a group of patients with mild-to-moderate coronavirus disease 2019 (COVID-19).

Methods: We studied 56 COVID-19 patients and 37 matched controls using magnetic resonance imaging (MRI). Cognition was assessed using Montreal Cognitive Assessment and Cambridge Neuropsychological Test Automated Battery, and fatigue was assessed using Chalder Fatigue Scale (CFQ-11). T1-weighted MRI was used to assess GM thickness and volume. Fiber-specific apparent fiber density (FD), free water index, and diffusion tensor imaging data were extracted using diffusion-weighted MRI (d-MRI). d-MRI data were correlated with clinical and cognitive measures using partial correlations and general linear modeling.

Results: COVID-19 patients had mild-to-moderate acute illness (95% non-hospitalized). The average period between real-time quantitative reverse transcription polymerase chain reaction-based diagnosis and clinical/MRI assessments was 93.3 (±26.4) days. The COVID-19 group had higher total CFQ-11 scores than the control group (p < 0.001). There were no differences in neuropsychological performance between groups. The COVID-19 group had lower FD in the association, projection, and commissural tracts, but no change in GM. The corona radiata, corticospinal tract, corpus callosum, arcuate fasciculus, cingulate, fornix, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus were involved. CFQ-11 scores, performance in reaction time, and visual memory tests correlated with microstructural changes in patients with COVID-19.

Conclusions: Quantitative d-MRI detected changes in the WM microstructure of patients recovering from COVID-19. This study suggests a possible brain substrate underlying the symptoms caused by SARS-CoV-2 during medium- to long-term recovery.

Source: Bispo DDC, Brandão PRP, Pereira DA, Maluf FB, Dias BA, Paranhos HR, von Glehn F, de Oliveira ACP, Regattieri NAT, Silva LS, Yasuda CL, Soares AASM, Descoteaux M. Brain microstructural changes and fatigue after COVID-19. Front Neurol. 2022 Nov 10;13:1029302. doi: 10.3389/fneur.2022.1029302. PMID: 36438956; PMCID: PMC9685991. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685991/ (Full text)

Sleep and circadian rhythm alterations in myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID fatigue syndrome and its association with cardiovascular risk factors: A prospective cohort study

Abstract:

This study aimed to investigate circadian rhythm manifestations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients (including a subpopulation of long-COVID patients) and matched healthy controls while also exploring their association with cardiovascular health variables.

Thirty-one ME/CFS patients (75% females), 23 individuals diagnosed with post-COVID ME/CFS (56% females) and 31 matched healthy controls (68% females) were enrolled in this study. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Actigraphy data, collected over one week, were used to analyze the 24-h profiles of wrist temperature, motor activity, and sleep circadian variables in the study participants. Associations between lipid profile with endothelial dysfunction biomarkers (such as endothelin-1, ICAM-1 and VCAM-1) and with sleep and circadian variables were also studied.

No differences were found in these variables between the two group of patients. Patients showed lower activity and worse sleep quality than matched healthy controls, together with a worse lipid profile than controls, that was associated with disturbances in the circadian temperature rhythm. ICAM-1 levels were associated with plasma lipids in healthy controls, but not in patients, who showed higher levels of endothelin-1 and VCAM-1.

These findings suggest that lipid profiles in ME/CFS are linked to disrupted circadian rhythms and sleep patterns, likely due to endothelial dysfunction. Furthermore, they highlight the intricate relationship between sleep, circadian rhythms, and cardiovascular health in this condition.

Source: Zerón-Rugerio MF, Zaragozá MC, Domingo JC, Sanmartín-Sentañes R, Alegre-Martin J, Castro-Marrero J, Cambras T. Sleep and circadian rhythm alterations in myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID fatigue syndrome and its association with cardiovascular risk factors: A prospective cohort study. Chronobiol Int. 2024 Jul 22:1-12. doi: 10.1080/07420528.2024.2380020. Epub ahead of print. PMID: 39037125. https://pubmed.ncbi.nlm.nih.gov/39037125/

Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls

Abstract:

Background: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA).

Methods: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses.

Results: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; β=-0.018, p=.035), except in the QFS group (β=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658).

Conclusion: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels.

Source: Vroegindeweij A, Eijkelkamp N, van den Berg SAA, van de Putte EM, Wulffraat NM, Swart JF, Nijhof SL. Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls. Psychoneuroendocrinology. 2024 Jun 28;168:107117. doi: 10.1016/j.psyneuen.2024.107117. Epub ahead of print. PMID: 38986244. https://pubmed.ncbi.nlm.nih.gov/38986244/

Long COVID as a Disease of Accelerated Biological Aging: An Opportunity to Translate Geroscience Interventions

Abstract:

It has been four years since long COVID-the protracted consequences that survivors of COVID-19 face-was first described. Yet, this entity continues to devastate the quality of life of an increasing number of COVID-19 survivors without any approved therapy. Furthermore, there remains a paucity of clinical trials addressing the biological root causes of this disease. Notably, the symptoms of long COVID-including but not limited to exercise intolerance, cognitive impairment, orthostasis, and functional decline-are typically seen with advancing age.

Leveraging this similarity, we posit that Geroscience-which aims to target the biological drivers of aging to prevent age-associated conditions as a group-could offer promising therapeutic avenues for long COVID. Bearing this in mind, this review presents a framework for studying long COVID as a state of effectively accelerated biological aging. Thus, we comprehensively review here the role of biological hallmarks of aging in long COVID, identifying research gaps and proposing directions for future preclinical and clinical studies.

Source: Shafqat A, Masters MC, Tripathi U, Tchkonia T, Kirkland JL, Hashmi SK. Long COVID as a Disease of Accelerated Biological Aging: An Opportunity to Translate Geroscience Interventions. Ageing Res Rev. 2024 Jun 28:102400. doi: 10.1016/j.arr.2024.102400. Epub ahead of print. PMID: 38945306. https://www.sciencedirect.com/science/article/abs/pii/S1568163724002186