Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

Participants: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

Source: Vernon SD, Funk S, Bateman L, Stoddard GJ, Hammer S, Sullivan K, Bell J, Abbaszadeh S, Lipkin WI, Komaroff AL. Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2022 Jun 23;9:917019. doi: 10.3389/fmed.2022.917019. PMID: 35847821; PMCID: PMC9285104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285104/ (Full text)

The Qigong of Prolong Life With Nine Turn Method Relieve Fatigue, Sleep, Anxiety and Depression in Patients With Chronic Fatigue Syndrome: A Randomized Controlled Clinical Study

Abstract

Background: Chronic fatigue syndrome (CFS) is a complex disease of unknown etiology and mechanism. The purpose of this study was to investigate the effect of Prolong Life with Nine Turn Method (PLWNT) Qigong exercise on CFS focusing on fatigue, sleep quality, depression, and anxiety.

Methods: A total of 90 participants diagnosed with CFS were randomly assigned into two parallel groups: PLWNT and cognitive behavioral therapy (CBT). The participants in the PLWNT or CBT group participated in qigong exercise or cognitive behavior education program, respectively, once a week in-person and were supervised online during the remaining 6 days at home, over 12 consecutive weeks. The primary outcome was fatigue (Multi-dimensional Fatigue Inventory 20 [MFI-20]), and secondary outcomes were sleep quality (Pittsburgh Sleep Quality Index [PSQI]), anxiety, depression (Hospital Anxiety and Depression Scale [HADS]), and changes in the Neuropeptide Y (NPY) of peripheral blood.

Results: The within-group comparisons of the PLWNT and CBT groups revealed significant improvement in both groups in MFI-20, PSQI, and HADS scores (P < 0.05). No significant difference were found between the PLWNT and CBT groups, even though the effective rate of the PLWNT group was 62.22%, which is slightly than 50.00% of the CBT group. The fatigue scores in the PLWNT group were positively correlated with sleep degree (r = 0.315) and anxiety degree (r = 0.333), only anxiety degree (r = 0.332) was found to be positively correlated with fatigue in the CBT group. The analysis of peripheral blood showed that NPY decreased after PLWNT intervention but increased significantly in the CBT.

Conclusion: The PLWNT qigong exercise has potential to be an effective rehabilitation method for CFS symptoms including fatigue, sleep disturbance, anxiety, and depression. Future studies should expand study sample size for in-depth investigation to determine the optimal frequency and intensity of PLWNT qigong intervention in CFS patients. The study was registered in the ClinicalTrials.gov database on April 12, 2018, with registration number NCT03496961.

Source: Xie F, You Y, Guan C, Xu J, Yao F. The Qigong of Prolong Life With Nine Turn Method Relieve Fatigue, Sleep, Anxiety and Depression in Patients With Chronic Fatigue Syndrome: A Randomized Controlled Clinical Study. Front Med (Lausanne). 2022 Jun 30;9:828414. doi: 10.3389/fmed.2022.828414. PMID: 35847786; PMCID: PMC9280429. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280429/ (Full text)

Memory impairments in chronic fatigue syndrome patients

Abstract:

Background: Chronic Fatigue Syndrome (CFS) patients often report memory problems. Prior research has produced conflicting results on this topic. Episodic memory impairments appear to be robust, but tasks assessing other aspects of memory (e.g., working and semantic memory) show slower speed but no decrease in accuracy. This study examined whether the memory problems of CFS patients reflect slower responses. Methods: CFS patients were recruited from a specialist clinic. Sixty-seven patients carried out tasks measuring immediate recall, delayed recognition memory, logical reasoning and semantic processing. The control group were 126 healthy volunteers recruited from the general population.

Results: The CFS patients recalled fewer words and had poorer delayed recognition. The other tasks showed slower speed but no effect on accuracy.

Conclusions: CFS patients have poorer immediate recall and delayed recognition memory. The delayed recognition memory probably reflected the poorer immediate recall. Slower responding was present in three of the tasks, and it is possible that this also accounted for the reduced immediate recall.

Source:  Smith, Andrew. Memory impairments in chronic fatigue syndrome patients. wjpmr, 2022, 8(6), 50-54. ISSN 2455-3301 https://orca.cardiff.ac.uk/id/eprint/150176/1/article_1654063780_pub.pdf (Full text)

Dietary supplements, daily nutrient intake, and health-related quality of life among people with myalgic encephalomyelitis/chronic fatigue syndrome

There remains ambiguity surrounding the role of dietary supplementation and nutrient intake on the health status of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) patients, yet supplement use and dietary modification appear to be common among people with the condition. This pilot cross-sectional study aimed to investigate if supplement use or nutrient intake was associated with self-reported health-related quality of life (HRQoL) scores among Australians with ME/CFS.

The eligibility criteria for this study included being a resident of Australia, being aged between 18 and 65 years, and having received a formal diagnosis of ME/CFS from a physician. Participants completed a series of self-administered questionnaires querying sociodemographic information, symptom presentation, HRQoL, routine supplement use, and nutrient intake. The 36-item Short-Form Health Survey version 2 (SF-36) was employed to assess participants’ HRQoL. Daily nutrient intake was estimated from participants’ responses to the Dietary Questionnaire for Epidemiological Studies (Cancer Council Victoria, Australia). Multiple linear regression analysis was performed for each of the eight SF-36 domains. Age, gender, body mass index, employment, education were controlled variables in each model, with supplement and nutrient variables entered in a stepwise manner.

Twenty-four Australians with ME/CFS, 54.2% of which met the International Consensus Criteria case definition for ME/CFS, participated in the study. Three of the eight regression models were statistically significant, being the ‘role limitations due to physical health problems’ (adjusted R 2 = 0.733, P < 0.001), ‘bodily pain’ (adjusted R 2 = 0.544, P = 0.004), and ‘general health perceptions’ (adjusted R 2 = 0.743, P < 0.001) SF-36 domains. Positive associations were observed between HRQoL and the routine use of vitamin C (ß = 0.300, P = 0.042) and herbal supplements (ß = 0.618, P < 0.001), as well as daily saturated fat (ß = 0.860, P < 0.001), total folate (ß = 0.710, P < 0.001), and calcium intake (ß = 0.897, P = 0.003). However, the routine use of evening primrose oil supplements (ß = -0.385, P = 0.006) and daily intakes of alpha-linolenic acid (ß = −0.543, P = 0.001), long chain omega-3 fatty acids (ß = −0.431, P = 0.017), and iodine (ß = −0.602, P = 0.034) were negatively associated with HRQoL scores. None of the supplements or nutrients studied had consistent associations with HRQoL across the three significant regression models.

The findings of this pilot study suggest that there may be links between dietary supplementation and nutrient intake with HRQoL among people with ME/CFS. Future studies should investigate supplement use, daily nutrient intake, and their relationships with HRQoL and symptom presentation among people with ME/CFS longitudinally and compared with healthy controls to further elucidate the role of supplements and nutrient intake in the management of ME/CFS.

Read the full study HERE.

Source: Weigel, B., Eaton-Fitch, N., Passmore, R., Cabanas, H., Staines, D., & Marshall-Gradisnik, S. (2022). Dietary supplements, daily nutrient intake, and health-related quality of life among people with myalgic encephalomyelitis/chronic fatigue syndrome. Proceedings of the Nutrition Society, 81(OCE3), E80. doi:10.1017/S0029665122001057 https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/dietary-supplements-daily-nutrient-intake-and-healthrelated-quality-of-life-among-people-with-myalgic-encephalomyelitischronic-fatigue-syndrome/F837EC4FE783FFAEB44F66F7748C11F6 (Full text)

Semen raphani weakened the action of ginseng under chronic fatigue condition

Abstract:

Ethnopharmacological relevance: Fatigue is a kind of subhealth status and people paid much more attention on it. Ginseng is used to treating fatigue as a kind of qi -tonifying drug in Chinese medicine. In the traditional applications, there is a viewpoint that ginseng could not be used with semen raphani and supposed that semen raphani is a kind of qi regulating drug, which will reduce the qi invigorating effect of ginseng. However, the underlying combination mechanism of the two drugs remained unclear.

Aim of the study: The aim of this study is to explore whether ginseng can be used with semen raphani or not to remedy acute and chronic fatigue conditions.

Methods: We used normal and weight-bearing swimming method combined with appetite control animals. The biochemical indexes in energy metabolism, antioxidant, regulating endocrine system and immunity capacities were performed to explore the antagonism effect of semen raphani on ginseng under acute and chronic fatigue conditions. The serum and urine metabolomics were investigated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Fecal flora was analyzed via 16S rRNA amplicon sequencing.

Results: The combination of ginseng with semen raphani have no influence on acute fatigue effect compared with ginseng alone. Both can improve the exhausted swimming time, the activity of GSH-Px, LDH and Na+-K+-ATPase. Furthermore, the combination of ginseng with semen raphani can increase the urine volume of rats and down-regulate the content of AQP-3, which can alleviate the “fireness” side-effect of ginseng. But the abundance and diversity of bacterial are decreased under acute fatigue experiment. Both the combination of ginseng with semen raphani and ginseng alone can remedy chronic-fatigue. They can also regulate the endocrine system, immune system, citric acid cycle metabolism, tryptophan metabolism, fatty acid metabolism, glycolysis/gluconeogenesis, etc. Furthermore, they can promote substance metabolism and energy metabolism in qi deficiency rats, and increase the abundance and diversities of the flora. While with the increased content of semen raphani, the combination of ginseng and semen raphani weaken the capacity of antioxidant, lactic acid metabolism, energy metabolism, flora diversity and regulation of endocrine system.

Conclusion: Compared with ginseng alone, the combination of ginseng with semen raphani can weaken the qi invigorating ability under chronic fatigue condition. The more ratios of semen raphani is in the combination of the two drugs, the less the power of treating chronic fatigue is. Compared with ginseng alone, the combination of ginseng with semen raphani have no influence on the qi invigorating ability under actue fatigue experiment. But the combination of ginseng with semen raphani will benefit for the “fireness” side-effect of ginseng.

Source: Wang Y, Ma C, Dou D. Semen raphani weakened the action of ginseng under chronic fatigue condition. J Ethnopharmacol. 2022 Sep 15;295:115352. doi: 10.1016/j.jep.2022.115352. Epub 2022 May 19. PMID: 35598795. https://pubmed.ncbi.nlm.nih.gov/35598795/

The higher resting heart rate in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients compared to healthy controls: relation with stroke volumes

Abstract:

Introduction: In patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) a higher-than-normal resting heart rate has been reported in a number of studies. As heart rate is linked to stroke volume, the present study explored the relationship between the supine heart rate and stroke volume index in healthy controls and in ME/CFS patients. Moreover, as patients with a postural orthostatic tachycardia syndrome (POTS) during tilt testing, have a higher supine heart rate than patients with a normal heart rate and blood pressure response during tilting, these two patient groups were also compared.

Methods and results: From a database of individuals who had undergone tilt-testing, including supine Doppler measurements for stroke volume index calculation, we selected ME/CFS patients and healthy controls without evidence of hypotension or syncope. 474 ME/CFS patients were analyzed, 314 with a normal heart rate and blood pressure response and 160 with POTS during tilt-testing, and 56 healthy controls. Resting stroke volume indices were similar between the 3 groups. All 3 groups had an inverse relation between the resting stroke volume index and resting heart rate (all p<0.0001). The slope of the relation was not significantly different between the 3 groups. Using the upper limit of the 95% prediction interval for the heart rate of healthy controls, 46 (15%) of patients with a normal heart rate and blood pressure response had a resting heart rate above the upper limit, 248 (85%) a heart rate between the upper and lower limit. In 47 (29%) patients developing POTS the resting heart rate was above the upper limit, and in 113 (71%) patients within the upper limit and lower limit. This distribution was significantly different between the two patient groups (p=0.0001).

Conclusion: Patients and healthy controls showed a significant and inverse relation between the SVI and heart rate at rest. Already at rest heart rate in patients developing POTS during tilt-testing were higher compared to the patients with a normal heart rate and blood pressure response per unit of SVI, but the heart rate of the majority of all patients fell within the limits of normal of healthy controls. The difference of patients with heart rate above the upper limit versus between the upper limit and lower limit deserves further investigation and may have therapeutic implications.

Source: VAN CAMPEN, C (Linda) M.C.; VISSER, Frans C.. The higher resting heart rate in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients compared to healthy controls: relation with stroke volumes.. Medical Research Archives, [S.l.], v. 10, n. 6, june 2022. ISSN 2375-1924. Available at: https://esmed.org/MRA/mra/article/view/2891. Date accessed: 17 july 2022. doi: https://doi.org/10.18103/mra.v10i6.2891.

Comparison of the Degree of Deconditioning in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients with and without Orthostatic Intolerance

Abstract:

Background: Orthostatic intolerance (OI) is a core finding in individuals with myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS). Deconditioning is often proposed as an important determinant for OI. Deconditioning can be objectively classified using the predicted peak oxygen consumption (%VO2 peak) values as derived from cardiopulmonary exercise testing (CPET) and OI can be objectively quantified using cerebral blood flow (CBF) changes during tilt testing. Therefore, if deconditioning contributes to OI, a correlation between peak VO2 and the %CBF reduction is expected.

Methods and results: 18 healthy controls (HC) and 122 ME/CFS patients without hypotension or tachycardia on tilt testing were studied. Deconditioning was classified as follows: %VO2 peak ≥85%= no deconditioning, %VO2 peak 65-85%= mild deconditioning, %VO2 peak<65%= severe deconditioning. HC had higher %VO2 peak compared to ME/CFS patients (p<0.0001). ME/CFS patients had significantly larger CBF reduction than HC (p<0.0001). No relation between the degree of deconditioning by the %VO2 peak and the %CBF reduction in ME/CFS patients was found. Moreover, we separately analyzed ME/CFS patients without an abnormal CBF reduction. Despite equal CBF reductions compared to HC and large differences between these patients and the patients with an abnormal CBF reduction, cardiac index (CI) changes (measured by suprasternal Doppler) were significantly less compared to ME/CFS patients with an abnormal CBF reduction (p<0.0001) but larger than in HC (p=0.004). Despite these different hemodynamic findings, %VO2 values were not different between the two patient groups, argumenting again against the causative role of hemodynamic abnormalities in deconditioning.

Conclusion: In ME/CFS patients without hypotension or tachycardia there is no relation between the %VO2 peak during CPET and the %CBF and %CI reduction during tilt testing, whether or not patients have an abnormal CBF reduction during tilt testing. It suggests again that deconditioning does not play an important role in OI.

Source: VAN CAMPEN, C (Linda) M.C.; VISSER, Frans C.. Comparison of the Degree of Deconditioning in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients with and without Orthostatic Intolerance. Medical Research Archives, [S.l.], v. 10, n. 6, june 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2858>. Date accessed: 17 july 2022. doi: https://doi.org/10.18103/mra.v10i6.2858.

Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID

Abstract:

Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID.
Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022.
Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS.
Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.
Source: Tokumasu K, Honda H, Sunada N, Sakurada Y, Matsuda Y, Yamamoto K, Nakano Y, Hasegawa T, Yamamoto Y, Otsuka Y, Hagiya H, Kataoka H, Ueda K, Otsuka F. Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID. Medicina. 2022; 58(7):850. https://doi.org/10.3390/medicina58070850 https://www.mdpi.com/1648-9144/58/7/850/htm (Full text)

Animal Models for Neuroinflammation and Potential Treatment Methods

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown etiology and without effective treatment options. The onset of ME/CFS is often associated with neuroinflammation following bacterial or viral infection.

A positron emission tomography imaging study revealed that the degree of neuroinflammation was correlated with the severity of several symptoms in patients with ME/CFS. In animal studies, lipopolysaccharide- and polyinosinic-polycytidylic acid-induced models are thought to mimic the pathological features of ME/CFS and provoke neuroinflammation, characterized by increased levels of proinflammatory cytokines and activation of microglia.

In this review, we described the anti-inflammatory effects of three compounds on neuroinflammatory responses utilizing animal models. The findings of the included studies suggest that anti-inflammatory substances may be used as effective therapies to ameliorate disease symptoms in patients with ME/CFS.

Source: Tamura Y, Yamato M, Kataoka Y. Animal Models for Neuroinflammation and Potential Treatment Methods. Front Neurol. 2022 Jun 27;13:890217. doi: 10.3389/fneur.2022.890217. PMID: 35832182; PMCID: PMC9271866. https://pubmed.ncbi.nlm.nih.gov/35832182/  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271866/ (Full study)

An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes

Abstract:

Objectives: Patients with pelvic congestion syndrome (PCS) often report overlapping somatic symptoms and syndromes. The objective of this study was to explore the prevalence of co-existing symptoms and self-reported syndrome diagnoses among women with PCS and to inform future research hypotheses.

Methods: A brief online survey was offered to members of a PCS support group website. Responses were assessed for self-reported co-existing symptoms and formal diagnoses, including: chronic fatigue syndrome, fibromyalgia, postural tachycardia syndrome, irritable bowel syndrome, migraines, interstitial cystitis, and temporomandibular joint dysfunction.

Results: Of a total of 6000 members, there were 398 respondents; 232 (59%) had not yet been treated for PCS. Among these, the most prevalent co-existing symptoms were as follows: severe fatigue (72%), dizziness (63%), IBS symptoms (61%), brain fog (33%), migraines (49%), polyuria or dysuria (41%), excessive sweating (31%), TMJ pain (31%), and loose skin or lax joints (18%). These are much higher than reported for the general female population. The most commonly self-reported comorbid syndrome diagnoses for the overall group of 398 were: irritable bowel syndrome (29%), fibromyalgia (13%), spinal nerve problems (18%), interstitial cystitis (10%), postural tachycardia syndrome (9%), hypertension (11%), chronic fatigue syndrome (10%), and Ehlers-Danlos syndrome (6%). Other than with hypertension, these rates are variably higher than in the general population.

Conclusion: Several self-reported co-existing symptoms and syndromes are more prevalent in members of a PCS support group relative to the reported prevalence in the general population. More formal investigation is warranted to evaluate this finding and to investigate potential etiologic links. Ehlers-Danlos Syndrome appears to be common in self identifying PCS women.

Source: Smith SJ, Sichlau M, Sewall LE, Smith BH, Chen B, Khurana N, Rowe PC. An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes. Phlebology. 2022 Jul 13:2683555221112567. doi: 10.1177/02683555221112567. Epub ahead of print. PMID: 35831253. https://pubmed.ncbi.nlm.nih.gov/35831253/