ME Association regular research roundup

ME/CFS and Long Covid Research: 23 – 29 May 2023

The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight the studies that have particularly caught our interest and follow these with the full list of publications together with their abstracts (summaries).

RESEARCH INDEX

The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.

Audio commentary by Dr Katrina Pears

It’s been an incredibly busy week for research, with a number of preprint studies. There have been thirteen new ME/CFS studies and twenty-four new Long Covid studies this week.

We have highlighted one of the ME/CFS studies in more detail below:

Paper two (2) looks into the autoantibodies to selenium (Se) transporter Selenoprotein P (SELENOP). SELENOP is involved in Se transport to cells, maintains selenoenzymes in several tissues, plays a role in antioxidative defence and Se metabolism.

Similar symptoms to ME/CFS are also experienced in hypothyroidism, such as Hashimoto’s thyroiditis.  Recently, autoantibodies to the selenium transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto’s thyroiditis (HT) and shown to impair selenium transport and selenoprotein expression. The authors of this study “hypothesized that SELENOP-aAb are prevalent in CFS and impair thyroid hormone (TH) metabolism.”

The study looked at the selenium status in 167 CFS patients, 545 healthy controls, 39 patients with fibromyalgia and 24 with Long Covid.

A range of findings were found, but importantly the SELENOP-aAb prevalence was much higher in ME/CFS (9.6-15.6% in CFS versus 0.9-2.0% in controls), although results depend on the cut off levels used. Therefore, CFS patients are shown to have a high level of autoantibodies to selenium transporter. Furthermore, none of the patients in the FM or Long Covid groups were above the thresholds used.

This study is a large European collaboration from several research groups we commonly report on, including the Charité Fatigue Centre (Carmen Scheibenbogen’s group)and the University of Valencia (Elisa Oltra’s group). It is a shame therefore there was such an imbalance of numbers in the four groups which make comparisons difficult.

Unusually, patients were diagnosed with the Canadian Consensus for CFS (CCC) and/ or the definition from the Parkstad Clinic in Amsterdam and Valencia. There are no details of what these clinics use for their diagnostic criteria and what symptoms are required. Not using a common diagnostic criteria is also questionable when it is used in research. Details for the common diagnostic criteria used can be found here. Furthermore, there is no mention of ME (myalgic encephalomyelitis) and only chronic fatigue syndrome or CFS is used.

Results from this study are interesting as hypothyroidism and the resultant effect on selenium dependent enzymes (selenium (Se)-dependent deiodinase isozymes- DIO) are not readily detectable by regular laboratory analyses of the classic biomarkers of the thyroid hormone (TH) in blood. This may be another part of the puzzle and biomedical dysfunction within ME/CFS that we still need to further investigate.

Also this week:

  • We have previously reported on the use of cryotherapy with stretching exercises, paper ten (10) this week is a follow-up study from these authors, reporting on effects of treatment after four weeks. Results showed that reduced fatigue, reduced aortic stiffness, reduced symptom severity, and improved cognitive function were maintained following the four weeks after treatment.
  • Paper thirteen (13) is from the well-known research group van Campen and Visser and compares tilt-table tests at 20 degree and 70 degrees. Finding that the lower angle proved POTS (Postural tachycardia syndrome) less, which is crucial for diagnosis.

ME/CFS Research References and Abstracts 

1. Investigating antibody reactivity to the intestinal microbiome in severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Katharine A. Seton, Marianne Defernez, Andrea Telatin, Sumeet K. Tiwari, GeorgeM. Savva, Antonietta Hayhoe, Alistair Noble, Ana Carvalho, Steve James, Amolak Bansal, Thomas Wileman,  Simon R. Carding.

medRxiv [Preprint]

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease of unknown aetiology that is characterised by disabling chronic fatigue and involves both the immune and gastrointestinal (GI) systems.

Patients display alterations in GI microbiome with a significant proportion experiencing GI discomfort and pain and elevated blood biomarkers for altered intestinal permeability compared with healthy individuals.

To investigate a possible GI origin of ME/CFS we designed a feasibility study to test the hypothesis that ME/CFS pathogenesis is a consequence of increased intestinal permeability that results in microbial translocation and a breakdown in immune tolerance leading to generation of antibodies reactive to indigenous intestinal microbes.

Secretory IgA and serum IgG levels and reactivity to intestinal microbes were assessed in five pairs of severe ME/CFS patients and matched same-household healthy controls. For profiling serum IgG we developed IgG-Seq which combines flow-cytometry based bacterial cell sorting and metagenomics to detect mucosal IgG reactivity to the microbiome.

We uncovered evidence for immune dysfunction in severe ME/CFS patients that was characterised by reduced capacity and reactivity of serum IgG to stool microbes, irrespective of their source. This study provides the rationale for additional studies in larger cohorts of ME/CFS patients to further explore immune-microbiome interactions.

2. Autoantibodies to Selenoprotein P in Patients with Chronic Fatigue Syndrome Suggest Selenium Transport Impairment and Acquired Resistance to Thyroid Hormone

Qian Sun, Elisa Oltra, D. A. Janneke Dijck-Brouwer, Thilo Samson Chillon, Petra Seemann, Sabrina Asaad, Kamil Demircan, José Andrés Espejo-Oltra, Teresa Sánchez-Fito, Eva Martín-Martínez, Waldemar B Minich, Frits A. J. Muskiet, Lutz Schomburg.

SSRN [Preprint]

Highlights

  • Comprehensive analysis of Se and thyroid hormone in chronic fatigue syndrome.
  • Biomarkers of Se status, i.e., total Se, GPx3 and SELENOP correlate linearly.
  • Autoantibodies to SELENOP are relatively frequent in chronic fatigue syndrome.
  • ELENOP-aAb are associated with dysregulated GPx3 and DIO activities.
  • Strongly reduced urinary iodine reflects DIO suppression by SELENOP-aAb.

Abstract

Chronic Fatigue Syndrome (CFS) presents with symptoms similar to hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety. However, the typical thyroid hormone (TH) profile of elevated thyrotropin (TSH) and low thyroxine (T4) is not observed.

Recently, autoantibodies to the selenium transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto’s thyroiditis and shown to impair selenium transport and selenoprotein expression. We hypothesized that SELENOPaAb are prevalent in CFS and impair TH metabolism.

Selenium status in CFS (n=167) was compared to that of healthy controls (n=545). Two additional small groups were included, namely patients with fibromyalgia (FM; n=39), a disease often comorbid with CFS, and patients with post-COVID condition (n=24).

The serum/plasma Se biomarkers total Se, glutathione peroxidase (GPx3) and SELENOP levels showed linear correlations without reaching saturation, indicative of Se deficiency.

TSH and total T4 levels fitted within normal ranges, but relative total T3 (%TT3) was low, and relative rT3 (%rT3) was elevated in CFS. SELENOP-aAb prevalence was 9.6-15.6% in CFS versus 0.9-2.0% in controls, depending on cut-off for positivity.

An impairment of Se transport in SELENOP-aAb positive CFS patients is suggested by the lack of correlation between total Se and GPx3 activity. The same patients present with disturbed TH parameters, including low deiodinase (DIO) activity (SPINA-GD index) and particularly low urinary iodine as compared to controls (43.2 (16.0) vs. 89.0 (54.9) µg/L, P

3. Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact of self-reported fatigue and illness duration

Hollie Byrne, Elisha K Josev, Sarah J Knight, Adam Scheinberg, Katherine Rowe, Lionel Lubitz, Marc L Seal.

medRxiv [Preprint]

Abtract

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS.

We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited.

Lateralised whole and regional hypothalamus volumes, including the anterior–superior, superior tubular, posterior, anterior-inferior and inferior tubular subregions, were calculated from T1-weighted images.

When controlling for age, sex and intracranial volume, Bayesian linear regression revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a negative linear relationship between right anterior-superior volumes and fatigue severity was identified, which was absent in controls.

In addition, Bayesian ordinal regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group.

While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue and longer illness duration were associated with greater right anterior-superior and superior-tubular volumes, respectively.

These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.

4. Identifying Demographic Trends in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients Presenting with Fibromyalgia as a Comorbidity in the Nationwide Inpatient Sample Database

Arvind Vishnu Murali.

Masters Thesis [Icahn School of Medicine at Mount Sinai]

Abstract

This retrospective observational study investigates the demographic differences between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients with and without Fibromyalgia as a comorbidity using the Nationwide Inpatient Sample database.

Results reveal significant differences in demographics, including a higher proportion of females and a younger mean age in the Fibromyalgia group. Additionally, the Fibromyalgia group had lower in-hospital mortality, higher proportion of patients discharged home or to short-term hospitals, shorter lengths of stay, and lower hospital charges.

Despite having lower Elixhauser comorbidity scores, ME/CFS patients with Fibromyalgia had higher prevalence of certain conditions.

Limitations include missing data, and further research is warranted to refine ME/CFS definitions and develop personalized treatment plans. The study highlights the need for better understanding of ME/CFS mechanisms, correlations with comorbidities like Fibromyalgia, and potential predictors to improve diagnosis and treatment.

5. Service users’ and parents/carers’ experiences of a paediatric chronic fatigue service: A service evaluation

Hartley G, Purrington J.

Chronic Illness. 2023;0(0).

Abstract

Objectives: This service evaluation explored the experiences of families receiving care in a paediatric chronic fatigue service. The evaluation aimed to improve service provision across paediatric chronic fatigue services more widely.

Methods: Children and young people aged 7–18 years (n  =  25) and parents/carers (n  =  25) completed a postal survey exploring experiences of a paediatric chronic fatigue service. Quantitative data were analysed descriptively, and qualitative data were analysed using thematic analysis.

Results: Most service users and parents/carers (88%) agreed that the service met their needs, that they felt supported by staff, and most notably, a large portion (74%) reported the team increased their activity levels. A small number disagreed (7%) with statements relating to positive links with other services, ease of talking to staff and suitability of appointment type.

The thematic analysis revealed three themes: help managing chronic fatigue syndrome, experience of professional support and accessibility of service. Families reported benefiting from increased understanding of chronic fatigue syndrome, learning new strategies, the team linking with schools, feeling validated and mental health support. Accessibility was a particular problem including the service location, setup of appointments and difficulty contacting the team.

Discussion: The evaluation presents recommendations for paediatric Chronic Fatigue services to improve service user experiences.

6. Fighting Post-COVID and ME/CFS – development of curative therapies

Carmen Scheibenbogen, Judith T. Bellmann-Strobl, Cornelia Heindrich, Kirsten Wittke, Elisa Stein, Christiana Franke, Harald Prüss, Hannah Preßler, Marie-Luise Machule, Heinrich Audebert, Carsten Finke5, Hanna G. Zimmerman,  Birgit Sawitzki, Christian Meisel, Markus Tölle, Anne Krüger, Anna C. Aschenbrenner, Joachim L. Schultz, Marc D. Beyer, Markus Ralser, Michael Mülleder, Leif E. Sander, Frank Konietschke, Friedemann Paul, Silvia Stojanov, Lisa Bruckert, Dennis M. Hedderich, Franziska Knolle, Gabriela Riemekasten, Maria J. Vehreschild, Oliver A. Cornely, Uta Behrends and Susen Burock.

Frontiers in Medicine, Sec. Infectious Diseases: Pathogenesis and Therapy: Volume 10 – 2023

Abstract

The sequela of COVID-19 include a broad spectrum of symptoms that fall under the umbrella term post-COVID-19 condition or syndrome (PCS). I

mmune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation have been identified as potential mechanisms. However, there is heterogeneity in expression of biomarkers, and it is unknown yet whether these distinguish different clinical subgroups of PCS.

There is an overlap of symptoms and pathomechanisms of PCS with postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

No curative therapies are available for neither ME/CFS nor PCS. The mechanisms identified so far provide targets for therapeutic interventions. To accelerate the development of therapies, we propose evaluating drugs targeting different mechanisms in clinical trial networks using harmonized diagnostic and outcome criteria and subgrouping patients based on a thorough clinical profiling including a comprehensive diagnostic and biomarker phenotyping.

7. Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study

Gottschalk CG, Whelan R, Peterson D, Roy A.

International Journal of Molecular Sciences. 2023; 24(10):8713.

Abstract

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a multisystem chronic illness characterized by severe muscle fatigue, pain, dizziness, and brain fog. Many patients with ME/CFS experience orthostatic intolerance (OI), which is characterized by frequent dizziness, light-headedness, and feeling faint while maintaining an upright posture. Despite intense investigation, the molecular mechanism of this debilitating condition is still unknown.

OI is often manifested by cardiovascular alterations, such as reduced cerebral blood flow, reduced blood pressure, and diminished heart rate. The bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of endothelial nitric oxide synthase (eNOS) enzyme, is tightly coupled with cardiovascular health and circulation.

To explore the role of BH4 in ME/CFS, serum samples of CFS patients (n = 32), CFS patients with OI only (n = 10; CFS + OI), and CFS patients with both OI and small fiber polyneuropathy (n = 12; CFS + OI + SFN) were subjected to BH4 ELISA.

Interestingly, our results revealed that the BH4 expression is significantly high in CFS, CFS + OI, and CFS + OI + SFN patients compared to age-/gender-matched controls.

Finally, a ROS production assay in cultured microglial cells followed by Pearson correlation statistics indicated that the elevated BH4 in serum samples of CFS + OI patients might be associated with the oxidative stress response.

These findings suggest that the regulation of BH4 metabolism could be a promising target for understanding the molecular mechanism of CFS and CFS with OI.

8. Free-water-corrected diffusion and adrenergic/muscarinic antibodies in myalgic encephalomyelitis/chronic fatigue syndrome

Kimura, Y, Sato, W, Maikusa, N, et al. 

J Neuroimaging. 2023; 1– 7.

Abstract

Background and Purpose: Free-water-corrected diffusion tensor imaging (FW-DTI), a new analysis method for diffusion MRI, can indicate neuroinflammation and degeneration. There is increasing evidence of autoimmune etiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We used FW-DTI and conventional DTI to investigate microstructural brain changes related to autoantibody titers in patients with ME/CFS.

Methods: We prospectively examined 58 consecutive right-handed ME/CFS patients who underwent both brain MRI including FW-DTI and a blood analysis of autoantibody titers against β1 adrenergic receptor (β1 AdR-Ab), β2 AdR-Ab, M3 acetylcholine receptor (M3 AchR-Ab), and M4 AchR-Ab. We investigated the correlations between these four autoantibody titers and three FW-DTI indices—free water (FW), FW-corrected fractional anisotropy (FAt), and FW-corrected mean diffusivity—as well as two conventional DTI indices—fractional anisotropy (FA) and mean diffusivity. The patients’ age and gender were considered as nuisance covariates. We also evaluated the correlations between the FW-DTI indices and the performance status and disease duration.

Results: Significant negative correlations between the serum levels of several autoantibody titers and DTI indices were identified, mainly in the right frontal operculum. The disease duration showed significant negative correlations with both FAt and FA in the right frontal operculum. The changes in the FW-corrected DTI indices were observed over a wider extent compared to the conventional DTI indices.

Conclusions: These results demonstrate the value of using DTI to assess the microstructure of ME/CFS. The abnormalities of right frontal operculum may be a diagnostic marker for ME/CFS.

9. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review

Pollack B, von Saltza E, McCorkell L, Santos L, Hultman A, Cohen AK and Soares L.

Front. Rehabil. Sci. 4:1122673.

Abstract

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID's impact on female reproductive health.

We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation. Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID.

These associated illnesses, whose patients are 70%–80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth.

Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause.

We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.

10. Effects of whole-body cryotherapy and static stretching are maintained 4 weeks after treatment in most patients with chronic fatigue syndrome

Sławomir Kujawski, Paweł Zalewski, Beata R. Godlewska, Agnieszka Cudnoch-Jędrzejewska, Modra Murovska, Julia L. Newton, Łukasz Sokołowski, Joanna Słomko.

Cryobiology, 2023. [In press, Journal Pre-Proof]

Abstract

In the previous study, whole-body cryotherapy (WBC)+static stretching (SS) has been shown to reduce the severity of some symptoms in Chronic Fatigue Syndrome (CFS) noted just after the therapy. Here we consider the effects of treatment and explore the sustainability of symptom improvements at four weeks (one-month) follow-up.

Twenty-two CFS patients were assessed one month after WBC + SS programme. Parameters related to fatigue (Chalder Fatigue Questionnaire (CFQ), Fatigue Impact Scale (FIS), Fatigue Severity Scale (FSS)), cognitive function (Trial Making test part A and B (TMT A and TMT B and its difference (TMT B-A)), Coding) hemodynamic, aortic stiffness (aortic systolic blood pressure (sBP aortic)) and autonomic nervous system functioning were measured. TMT A, TMT B, TMT B-A and Coding improved at one month after the WBC + SS programme.

WBC + SS had a significant effect on the increase in sympathetic nervous system activity in rest. WBC + SS had a significant, positive chronotropic effect on the cardiac muscle. Peripheral and aortic systolic blood pressure decreased one month after WBC + SS in comparison to before.

Effects of WBC + SS on reduction of fatigue, indicators of aortic stiffness and symptoms severity related to autonomic nervous system disturbance and improvement in cognitive function were maintained at one month.

However, improvement in all three fatigue scales (CFQ, FIS and FSS) was noted in 17 of 22 patients. In addition, ten patients were treated initially but they were not assessed at 4 weeks, and are thus not included in the 22 patients who were examined on follow-up. The overall effects of WBC + SS noted at one month post-treatment should be interpreted with caution.

11. Chronic fatigue: What investigations? And what for?

B. Gramont, J. Goutte, L. Féasson, G. Millet, D. Hupin, P. Cathébras.

La Revue de Médecine Interne, 2023 May 27:S0248-8663(23)00593-3. [In Press, Corrected Proof] [Epub ahead of Print] [Article in French]

Abstract

Chronic fatigue is a frequent complaint, expressed at all levels of the healthcare system. It is perceived as disabling in a high proportion of cases, and internists are frequently called upon to find “the” cause.

The etiological diagnostic approach of an unexplained state of fatigue relies on the careful search for more specific clues by questioning and clinical examination. It is necessary to recognize the limited place of complementary examinations apart from the basic biological parameters. Simple rating scales can be useful in the etiological and differential diagnosis of fatigue.

Chronic fatigue syndrome (CFS), in the current state of knowledge, cannot be considered as a specific pathological entity distinct from idiopathic chronic fatigue states, and does not have validated biomarkers.

It is important to know that a state of chronic asthenia often results from several intricated etiological factors (biological, psychological and social), to be classified as predisposing, precipitating and perpetuating.

The metabolic and cardiorespiratory exercise test has a major place in the assessment and management of fatigue, as a prerequisite for personalized retraining or adapted physical activity (APA), which are the treatments of choice for chronic fatigue.

12. Intestinal bacteria associated with irritable bowel syndrome and chronic fatigue

El-Salhy M.

Neurogastroenterol Motil. 2023 May 29:e14621. [Epub ahead of print.]

Abstract

The etiology of irritable bowel syndrome (IBS) is unknown. Abnormal intestinal bacterial profiles and low bacterial diversity appear to play important roles in the pathophysiology of IBS.

This narrative review was designed to present recent observations made relating to fecal microbiota transplantation (FMT), which implicate possible roles of 11 intestinal bacteria in the pathophysiology of IBS.

The intestinal abundances of nine of these bacteria increased after FMT in patients with IBS, and these increases were inversely correlated with IBS symptoms and fatigue severity. These bacteria were Alistipes spp., Faecalibacterium prausnitzii, Eubacterium biforme, Holdemanella biformis, Prevotella spp., Bacteroides stercoris, Parabacteroides johnsonii, Bacteroides zoogleoformans, and Lactobacillus spp.

The intestinal abundances of two bacteria were decreased in patients with IBS after FMT and were correlated with the severity of IBS symptoms and fatigue (Streptococcus thermophilus and Coprobacillus cateniformis).

Ten of these bacteria are anaerobic and one (Streptococcus thermophilus) is facultative anaerobic. Several of these bacteria produce short-chain fatty acids, especially butyrate, which is used as an energy source by large intestine epithelial cells.

Moreover, it modulates the immune response and hypersensitivity of the large intestine and decreases intestinal cell permeability and intestinal motility. These bacteria could be used as probiotics to improve these conditions. Protein-rich diets could increase the intestinal abundance of Alistipes, and plant-rich diet could increase the intestinal abundance of Prevotella spp., and consequently improve IBS and fatigue.

13. Comparison of a 20 degree and 70 degree tilt test in adolescent myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients

van Campen CLMC, Rowe PC, Visser FC.

Front Pediatr. 2023 May 12;11:1169447.

Abstract

Introduction: During a standard 70-degree head-up tilt test, 90% of adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develop an abnormal reduction in cerebral blood flow (CBF). A 70-degree test might not be tolerated by young ME/CFS patients because of the high incidence of syncopal spells. This study examined whether a test at 20 degrees would be sufficient to provoke important reductions in CBF in young ME/CFS patients.

Methods: We analyzed 83 studies of adolescent ME/CFS patients. We assessed CBF using extracranial Doppler measurements of the internal carotid and vertebral arteries supine and during the tilt. We studied 42 adolescents during a 20 degree and 41 during a 70 degree test.

Results: At 20 degrees, no patients developed postural orthostatic tachycardia (POTS), compared to 32% at 70 degrees (p = 0.0002). The CBF reduction during the 20 degree tilt of -27(6)% was slightly less than during the reduction during a 70 degree test [-31(7)%; p = 0.003]. Seventeen adolescents had CBF measurements at both 20 and 70 degrees. The CBF reduction in these patients with both a 20 and 70 degrees test was significantly larger at 70 degrees than at 20 degrees (p < 0.0001).

Conclusions: A 20 degree tilt in young ME/CFS patients resulted in a CBF reduction comparable to that in adult patients during a 70 degree test. The lower tilt angle provoked less POTS, emphasizing the importance of using the 70 degree angle for that diagnosis. Further study is needed to explore whether CBF measurements during tilt provide an improved standard for classifying orthostatic intolerance.

Long-COVID Research References

  1. Changes in the proteomics of exhaled breath condensate under the influence of inhaled hydrogen in patients with post-COVID syndrome
  2. Autonomic Nervous System Affection Due to Post-Covid Syndrome
  3. Rheumatology and Long COVID: lessons from the study of fibromyalgia
  4. Minimal Objective Autonomic Dysfunction in Long-COVID
  5. Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC)
  6. Pre-existing sleep problems as a predictor of post-acute sequelae of COVID-19
  7. Risks of digestive diseases in long COVID: Evidence from a large-scale cohort study
  8. Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in patients with and without long COVID
  9. How Does Long-COVID Impact Prognosis and the Long-Term Sequelae?
  10. Trajectory of Gastrointestinal Symptoms in Previously Hospitalized COVID-19 Survivors: The Long COVID Experience Multicenter Study
  11. A systematic review and meta-analysis of long COVID symptoms
  12. Etiological factors of chronic pain syndrome in young adults with post-coronavirus disease 2019 condition
  13. The Leipzig Treatment Program for Interdisciplinary Diagnosis and Therapy of Neurocognitive Post-COVID Symptoms
  14. The association between the number of symptoms and the severity of Post-COVID-Fatigue after SARS-CoV-2 infection treated in an outpatient setting
  15. Diagnostic value of 24-h ECG recording in Long COVID patients with postural orthostatic tachycardia syndrome 
  16. Psychiatric consequences and issues of long Covid on patients with prior psychiatric comorbidities. A scoping review
  17. The Remote Diet Intervention to REduce long Covid symptoms Trial (ReDIRECT) – dietary profile of the study participants at baseline
  18. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
  19. Do Pre-existing Sleep Disorders Worsen Long COVID Fatigue and Brain Fog?
  20. Psychiatric symptoms in Long-COVID patients: a systematic review
  21. The plasma metabolome of long COVID-19 patients two years after infection
  22. Adaptive Immunity Dysregulation Is Associated to the Development of Long Covid
  23. Unique Differentiation and Homing Features of T Cells in Individuals with Long Covid
  24. Progress and treatment of “long COVID” in non-hospitalized patients: A single-center retrospective cohort study

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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