The ME Association ME/CFS (& Long Covid) Weekly Research Round-up

June 18, 2021


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

All research relating to ME/CFS can be located in the ME Association: Index of ME/CFS Published Research. It is a free resource and available to anyone.

This extensive library of research is normally updated at the end of each month, but with the change in staff, it will be updated again by 01 July 2021.

The Index provides an A-Z of published research studies, selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis, myalgic encephalopathy, and/or chronic fatigue syndrome (ME/CFS).

You can use it to easily locate and read any research that you might be interested in regard to, e.g., epidemiology, infection, neurology, post-exertional malaise etc.

You can also find the Research Index in the Research section of the website together with a list of Research Summaries that provide more detailed lay explanations of the more interesting work that has been published to date.

ME/CFS Research Published 05 June –  11 June 2021 

Seven new research studies on ME/CFS have been published during this period and we have also included eight studies on Long Covid. We highlight two on ME/CFS from the selection below: 

The first two studies (1) and (2) from the same research team, employed cardio-pulmonary exercise testing (CPET) in female and then male ME/CFS cohorts. They compared them to people with idiopathic chronic fatigue (people who don’t meet the full ME/CFS diagnostic criteria). The studies tested exercise intolerance and showed a reduced tolerance in people with ME/CFS confirming what we have seen from other studies that use CPET testing.

The seventh (7) study examined daily diet and supplement use by people with ME/CFS compared to the general Australian population. As well as diet and supplement effect on perceived health-related quality of life. The study was conducted through questionnaires, finding a large variation between the two groups. Although the perceived effect of diet and supplements on health-related quality of life was unclear, they are determined to be of value to people with the condition.  

ME/CFS Research References and Abstracts 

1. Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol 

Van Campen CMC and Visser FC; Healthcare 2021, 9(6), 68 

Abstract 

Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients, using the golden standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls.

No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfil the ME/CFS criteria in a female population and hypothesized a different pattern of response would be present during the 2nd day CPET.  

Methods: Fifty-one female patients with ICF completed a 2-day CPET protocol and were compared to an age/sex-matched group of 50 female ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities.  

Results: Baseline characteristics for both groups were similar for age, BMI, BSA, and disease duration. A significance difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001). ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload.  

Conclusion: This study confirms that female ME/CFS patients have a reduction in exercise capacity in response to a second day CPET. These results are similar to published results in female ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls. 

2. Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol 

Van Campen CMC and Visser FC; Healthcare 2021, 9(6), 683 

Abstract 

Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS ) patients, using the gold standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET).

A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls. No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfil the ME/CFS criteria in a male population and hypothesized a different pattern of response would be present during the 2nd day CPET.   

Methods: We compared 25 male patients with ICF who had completed a 2-day CPET protocol to an age-/gender-matched group of 26 male ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities.   

Results: Baseline characteristics for both groups were similar for age, body mass index (BMI), body surface area, (BSA), and disease duration. A significant difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs. zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001).

ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload.   

Conclusion: This study confirms that male ME/CFS patients have a reduction in exercise capacity in response to a second-day CPET. These results are similar to published results in male ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls. 

3. Predicting post-exertional malaise in Gulf War Illness based on acute exercise responses 

Boruch AE, Lindheimer JB, Klein-Adams JC, Stegner AJ, Wylie GR, Ninneman JV, Alexander T, Gretzon NP, Samy B, Van Riper SM, Falvo MJ, Cook DB; Life Sci. 2021 Jun 10:119701. 

Abstract 

Aims: Post-exertional malaise (PEM) is poorly understood in Gulf War Illness (GWI). Exercise challenges have emerged as stimuli to study PEM; however, little attention has been paid to unique cardiorespiratory and perceptual responses during exercise. This study tested whether select exercise parameters explained variability in PEM responses. 

Main methods: Visual analog scale (0-100) versions of the Kansas questionnaire were used for daily symptom measurements one week before and one week after 30-min of cycling at 70% heart rate reserve in 43 Veterans with GWI and 31 Veteran controls (CON). Cardiopulmonary exercise testing (CPET) methods were used to measure oxygen (VO2), carbon dioxide (VCO2), ventilation (VE), heart rate, work rate, and leg muscle pain.

Symptom changes and CPET parameters were compared between groups with independent samples t-tests. Linear regression (GLM) with VE/V CO2, cumulative work, leg muscle pain, and self-reported physical function treated as independent variables and peak symptom response as the dependent variable tested whether exercise responses predicted PEM. 

Key findings: Compared to CON, Veterans with GWI had greater ventilatory equivalent for oxygen (VE/VO2), peak leg muscle pain, fatigue, and lower VCO2, VO2, power, and cumulative work during exercise (p < 0.05), and greater peak symptom responses (GWI = 38.90 ± 29.06, CON = 17.84 ± 28.26, g = 0.70, p < 0.01). The final GLM did not explain significant variance in PEM (Pooled R2 = 0.15, Adjusted R2 = 0.03, p = 0.34). 

Significance: The PEM response was not related to the selected combination of cardiorespiratory and perceptual responses to exercise. 

4. The Prevalence of Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in a Community‑Based Sample 

Jason LA, Katz BZ, Sunnquist M, Torres C, Cotler J, Bhatia S; Child Youth Care Forum. 2020 Aug;49(4):563-579 

Abstract 

Background: Most pediatric prevalence studies of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) have been based upon data from tertiary care centers, a process known for systematic biases such as excluding youth of lower socioeconomic status and those less likely to have access to health care.

In addition, most pediatric ME/CFS epidemiologic studies have not included a thorough medical and psychiatric examination. The purpose of this study was to determine the prevalence of pediatric ME/CFS from an ethnically and sociodemographically diverse community-based random sample. 

Method: A sample of 10,119 youth aged 5-17 from 5622 households in the Chicagoland area were screened. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for three selected case definitions. A probabilistic, multi-stage formula was used for final prevalence calculations. 

Results: The prevalence of pediatric ME/CFS was 0.75%, with a higher percentage being African American and Latinx than Caucasian. Of the youth diagnosed with ME/CFS, less than 5% had been previously diagnosed with the illness. 

Conclusions: Many youth with the illness have not been previously diagnosed with ME/CFS. These findings point to the need for better ways to identify and diagnose youth with this illness.  

5. Insights from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome 

Komaroff AL and Lipkin WI; Trends in Molecular Medicine (2021) 

Abstract  

SARS-CoV-2 can cause chronic and acute disease. Post-Acute Sequelae of SARSCoV-2 infection (PASC) include injury to the lungs, heart, kidneys and brain, that may produce a variety of symptoms. PASC also includes a post-COVID-19 syndrome (“long COVID”) with features that can follow other acute infectious diseases as well as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Here we summarize what is known about the pathogenesis of ME/CFS and of acute COVID-19 and speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses and suggest a research agenda for both ME/CFS and postCOVID-19 syndrome.  

6. Post-Acute COVID-19 Symptoms, a Potential Link with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A 6-Month Survey in a Mexican Cohort 

González-Hermosillo, JA.; Martínez-López, J.P.; Carrillo-Lampón, S.A.; Ruiz-Ojeda, D.; Herrera-Ramírez, S.; Amezcua-Guerra, L.M.; Martínez-Alvarado, M.d.R. ; Brain Sci. 2021, 11, 760 

Abstract

The aim of this study was to describe the clinical evolution during 6 months of follow-up of adults recovered from COVID-19. We tried to determine how many met the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

A total of 130 patients (51.0 ± 14 years, 34.6% female) were enrolled. Symptoms were common, participants reported a median number of 9 (IQR 5–14) symptoms. Fatigue was the most common symptom (61/130; 46.9%). Patients with fatigue were older 53.9 ± 13.5 years compared with 48.5 ± 13.3 years in those without fatigue (p = 0.02) and had a longer length of hospital stay, 17 ± 14 days vs. 13 ± 10 days (p = 0.04).

There was no difference in other comorbidities between patients with fatigue and those without it, and no association between COVID-19 severity and fatigue. After multivariate adjustment of all baseline clinical features, only age 40 to 50 years old was positively associated with fatigue, OR 2.5 (95% CI 1.05–6.05) p = 0.03.

In our survey, only 17 (13%) patients met the Institute of Medicine’s criteria for “systemic exertion intolerance disease,” the new name of ME/CFS. In conclusion, in some patients, the features of post-acute COVID-19 syndrome overlap with the clinical features of ME/CFS.  

7. A preliminary investigation of nutritional intake and supplement use in Australians with myalgic encephalomyelitis/chronic fatigue syndrome and the implications on health-related quality of life  

Weigel, B., Eaton-Fitch, N., Passmore, R., Cabanas, H., Staines, D., & Marshall-Gradisnik, S.; Food & Nutrition Research, 65. 

Abstract 

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem illness without a currently recognized pharmacological treatment. Dietary supplementation and modification have been posited as potential management strategies; however, their efficacy is controversial. 

Objective: This study aimed to assess the nutritional intake and supplement use of Australian ME/CFS patients and the perceived effect on health-related quality of life (HRQoL) for the first time in an Australian patient population. 

Design: Between February 2019 and January 2020, ME/CFS patients across Australia volunteered in this cross-sectional study in response to online advertisements. Eligible respondents were invited to complete three online self-administered questionnaires investigating their supplement use, nutritional intake, and HRQoL.

The study participants’ supplement use and nutritional intake were summarized and compared with the population data returned from the Australian Health Survey (2011–2012). Multiple linear regression analysis was also performed to determine the effect of participants’ supplement use and nutrient intake on HRQoL. 

Results: Twenty-four eligible ME/CFS patients (54.2% meeting the International Consensus Criteria, 79.2% female, mean age = 43.4 ± 10.5 years) completed the online questionnaires. Supplement use was highly prevalent among the study sample (87.5%) and considerably more common when compared with population data (31.9%). Daily total fats and caffeine intakes were significantly higher among ME/CFS patients when compared with the Australian population (P = 0.009 and P = 0.033, respectively), whereas daily intakes of total carbohydrates and alcohol were significantly lower (both P < 0.001). No consistent trends between nutrition and supplement use with patients’ HRQoL could be identified. 

Conclusions: The daily diet and supplement use of ME/CFS patients appear to vary considerably from those of the general Australian population. Although the role of nutritional intake and supplement use on ME/CFS patients’ HRQoL remains unclear, dietary changes and the use of supplements appear to be of value to ME/CFS patients. 

Long-COVID Research References  

  1. COVID-19: long covid and its societal consequences 
  2. Interleukin-6 as potential mediator of long-term neuropsychiatric symptoms of COVID-19 
  3. Long COVID-19 or Post-Acute Sequelae of SARS-CoV-2 Infection in Children, Adolescents, and Young Adults 
  4. Pediatric long-COVID: An overlooked phenomenon? 
  5. Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients 
  6. Long-term consequences in critically ill COVID-19 patients: a prospective cohort study 
  7. Altered tryptophan absorption and metabolism could underlie long-term symptoms in survivors of coronavirus disease 2019 (COVID-19) 
  8. Transcranial direct current stimulation as a strategy to manage COVID-19 pain and fatigue 

Katrina Pears, Research Correspondent, ME Association

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