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Frequency and severity of symptoms. a Stacked bar charts represent the frequency and severity of symptoms as indicated on the first page of the Munich Berlin Symptom Questionnaires (MBSQs). Symptoms that are assessed differently in pediatric (n = 4) and adult patients (n = 6) are presented separately, as indicated. b Stacked bar charts display the frequency and severity of symptoms from the second page of the Munich Berlin Symptom Questionnaires (MBSQs). Symptoms that are assessed differently in pediatric (n = 4) and adult patients (n = 6) are presented separately, as indicated. *New difficulties with math or other educational subject; **Marked weight change and/or loss of appetite and/or abnormal appetite; ***New sensitivities to food, medication or chemicals
Source publication
A subset of patients with post-COVID-19 condition (PCC) fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To establish the diagnosis of ME/CFS for clinical and research purposes, comprehensive scores have to be evaluated. We developed the Munich Berlin Symptom Questionnaires (MBSQs) and supplementary scor...
Citations
... Additionally, there are a number of criteria catalogs for diagnosing ME/CFS based on the symptoms present; the rather unspecific 1994 Centers for Disease Control and Prevention (CDC) Fukuda criteria (known as CDC or Fukuda criteria) [18] have been replaced by the Canadian Consensus Criteria (CCC), Criteria of the Institute of Medicine (IOM), or the International Consensus Criteria (ICC) [19][20][21][22]. Additionally, a variety of questionnaire tools (e.g., Munich Berlin Symptom Questionnaire (MBSQ) [23], DePaul Symptom Questionnaire (PSQ) [24]) are available for clinical practice. ...
... Apart from one study that designed its own instrument based on the CDC Fukuda criteria [34], all other studies used validated questionnaires. In their only recently published DACH consensus statement on ME/CFS, Hoffmann et al. [14] also suggest an equally broad selection of questionnaires to support the assessment of pathological fatigue in ME/CFS, e.g., Fatigue Assessment Scale (FAS [127]) and MBSQ [23]. The use of such a wide range of instruments suggests that there is no consensus on which tool is appropriate for assessing fatigue as an outcome measure in the clinical-experimental setting. ...
Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmunological disorder with limited treatment options. Despite the widespread use of Dietary Supplements (DSs) among ME/CFS patients to alleviate fatigue and associated symptoms, evidence remains inconclusive. This systematic review aims to provide an updated synthesis of the efficacy of DS interventions and explore possible mechanisms underlying their therapeutic effects. Methods: This systematic review was conducted according to PRISMA guidelines. Several databases (Ebsco Host, PubMed, Scopus, Google Scholar) were used for the systematic search, which was based on the broad search terms ME/CFS and DS with a focus on publications between 1994 and 2024. The primary outcome was fatigue, with additional considerations including psychological well-being, physical activity, and biochemical markers. Two independent researchers screened the studies for eligibility in a multi-stage process and assessed quality and bias using Cochrane’s risk of bias tools (RoB-2, ROBINS-I). Results: Fourteen studies (N = 809) of heterogeneous designs were included, showing a high risk of bias, mostly due to missing data and selection bias. While some interventions (L-carnitine and guanidinoacetic acid, oxaloacetate, CoQ10–selenium combination, NADH and NADH-CoQ10 combination) showed significant reductions in fatigue, methodological limitations, like small sample sizes and missing data, prevent firm conclusions. Mixed results were reported for secondary outcomes like cognitive function and inflammatory markers. Six studies noted adverse effects, including nausea and insomnia. Conclusions: Though some DSs showed potential in reducing fatigue in ME/CFS, methodological limitations and inconsistent results hinder definitive conclusions. Future research should improve diagnostic criteria and include more diverse populations.
... Another crucial aspect before prescribing exercise training is to assess for PEM (by clinical interview and if suspected by using the DePaul Symptom Questionnaire-Post-Exertional Malaise, DSQ-PEM) [54]. PEM is also the cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and therefore in long COVID cases with PEM, diagnostic ME/CFS criteria (Canadian Consensus or IOM criteria) should be checked [55,56]. If there are no signs of PEM, a "conventional" exercise training program that combines moderate to intense endurance and strength training may be used. ...
... It appears that the current coronavirus pandemic could trigger a global spike in CFS/ME within 6 to 18 months of discharge. Preventing the continuation of chronic fatigue and controlling its adverse consequences can be achieved by examining and intervening in the factors that determine the occurrence of this syndrome and the effective factors in reducing the quality of life of these patients (17,18). ...
Introduction: The COVID-19 pandemic has been a tragedy. It has devastated the health and financial well-being of many people around the world. Fatigue is one of the common symptoms and complications of covid-19, which can continue in patients for a long time after infection. The present study was also conducted with the aim of determining the prevalence of chronic fatigue syndrome and associated risk factors in covid-19 patients discharged from at northwest of Iran hospitals in 2022 Methods This cross-sectional study was performed between May 2021 and January 2022 at northwest of Iran. 422 patients who had been discharged from hospital with COVID-19 were enrolled in our study. Chalder fatigue Assessment Scale (FAS) was used to measure post-COVID-19 chronic fatigue syndrome. Central and dispersion indicators were used to describe clinical and sociodemographic characteristics of patients. The chi-square test and person correlation were used to examine the statistical association between the CFS score and other clinical and sociodemographic factors. Results in overall, 72% of patients were female. The mean ± SD of the CFS score was 21.2 ± 9.0. The prevalence of post-COVID-19 CFS among our studied sample was %12.64. The findings showed that the prevalence of chronic fatigue and fatigue scores were higher in women (%13) than in men (%12.3) and this difference was statistically significant (P < 0.04). The findings showed that the prevalence of chronic fatigue with history of previous disease (P = 0.04), history of drug use (P = 0.01), history of smoking (P = 0.04), history of mechanical ventilation (P = 0.05) and age (P = 0.001) has a significant relationship. Conclusion Post-COVID-19 fatigue is a major issue following the initial acute illness with COVID-19, with a prevalence of %12.64. Therefore, the implementation of standardized measures for the screening of chronic fatigue after covid-19 and planning by the health staff in order to help these patients especially among female patients Seems necessary.
... Schwere Verläufe mit deutlich eingeschränkter Teilhabe sind möglich [255], darunter gemäß eigenen Beobachtungen bei Adoleszenten auch einzelne Fälle mit postviralem ME/CFS [54]. Zu möglichen Risikofaktoren für PCS bei Kindern und Jugendlichen liegen nur wenige Daten vor. ...
... und können von dort angefragt werden (sekretariat.mcfc@mri.tum.de), darunter auch der übersetzte DSQ-PEM und der neu entwickelte MBSQ für die ME/CFS-Diagnostik [54,58] ...
... The presence, severity, and duration of PEM were evaluated by the well-established De-Paul Symptom Questionnaire for PEM (DSQ-PEM) [34]. The frequency and severity of ME/CFS symptoms were assessed in a quantitative manner using the 5-point Likert scale derived from the DePaul Symptom Questionnaire via the novel Munich Berlin Symptom Questionnaire (MBSQ) [19]. Using the MBSQ's diagnostic algorithms, up to four sets of internationally established diagnostic criteria were evaluated, including the CCC and IOM criteria, recommended by the European Network on ME/CFS (EUROMENE) [35] and the Centers for Disease Control and Prevention (CDC) [43] as well as, in the case of children and adolescents, the age-adapted CDW-R [2] and the PCD-J [44]. ...
... It is estimated that 19-58% of patients with PASC, also known as post-COVID-19 condition (ICD-10 CM U09.9), meet the diagnostic criteria for ME/CFS [15,18,64]. We recently described ME/CFS following COVID-19 in children as young as 11-14 years, with severe impact on their daily function [19]. Our user-friendly MECFS-R, with its standard dataset, novel questionnaires such as the MBSQ [19], and accompanying information, can help PASC teams develop local standard approaches diagnosing and phenotyping ME/CFS following COVID-19. ...
... We recently described ME/CFS following COVID-19 in children as young as 11-14 years, with severe impact on their daily function [19]. Our user-friendly MECFS-R, with its standard dataset, novel questionnaires such as the MBSQ [19], and accompanying information, can help PASC teams develop local standard approaches diagnosing and phenotyping ME/CFS following COVID-19. ...
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystemic disease characterized by a complex, incompletely understood etiology. Methods: To facilitate future clinical and translational research, a multicenter German ME/CFS registry (MECFS-R) was established to collect comprehensive, longitudinal, clinical, epidemiological, and laboratory data from adults, adolescents, and children in a web-based multilayer-secured database. Results: Here, we present the research protocol and first results of a pilot cohort of 174 ME/CFS patients diagnosed at two specialized tertiary fatigue centers, including 130 (74.7%) adults (mean age 38.4; SD 12.6) and 43 (25.3%) pediatric patients (mean age 15.5; SD 4.2). A viral trigger was identified in 160/174 (92.0%) cases, with SARS-CoV-2 in almost half of them. Patients exhibited severe functional and social impairment, as reflected by a median Bell Score of 30.0 (IQR 30.0 to 40.0) and a poor health-related quality of life assessed with the Short Form-36 health survey, resulting in a mean score of 40.4 (SD 20.6) for physical function and 59.1 (SD 18.8) for mental health. Conclusions: The MECFS-R provides important clinical information on ME/CFS to research and healthcare institutions. Paired with a multicenter biobank, it facilitates research on pathogenesis, diagnostic markers, and treatment options. Trial registration: ClinicalTrials.gov NCT05778006.
... It is estimated that 19-58% patients with PASC, also known as post COVID-19 condition (ICD-10 U09.9!), meets the diagnostic criteria for ME/CFS [15,18], representing up to about 50% of patients at healthcare institutions specialized in severe forms of PASC [55]. We recently described ME/CFS following COVID-19 in children as young as 11-14 years, with severe impact on their daily function [56]. Our user-friendly MECFS-R, with its standard dataset, novel questionnaires such as the MBSQ [19], and accompanying information can help PASC teams in developing local standard approaches diagnosing and phenotyping ME/CFS following COVID-19. ...
... (26%) in our first cohort. Non-infectious triggers are most likely underrepresented since both recruiting centers are focusing on post-infectious ME/CFS as immunological departments [55,56,68]. However, the registry allows a very precise documentation of triggering events including clinical and laboratory data from the time of initial symptoms, and therefore facilitates a stratification of study participants along confirmed versus probable and selfreported triggers. ...
... The physical and social functioning of MECFS-R participants was severely reduced as indicated by low Bell and SF-36 scores, while higher scores were found for emotional role functioning and psychological well-being [70,71]. This aligns with earlier reports indicating that the HRQoL of patients with ME/CFS compared to other chronic diseases is severely compromised, mainly due to physical impairment [55, 56,68,72] Moreover, in support of published results [73], MECFS-R participants suffered from significant autonomic dysfunction as indicated by high COMPASS-31 scores. We recommend the Bell score, SF-36, and COMPASS-31 as standard measures for clinical phenotyping to facilitate both local medical care as well as future studies with secondary use of MECFS-R data. ...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multi-systemic disease characterized by a complex, incompletely understood etiology. To facilitate future clinical and translational research, a multicenter German ME/CFS registry was established to collect comprehensive, longitudinal, clinical, epidemiological, and laboratory data from adults, adolescents, and children in a web-based multilayer-secured database.
Here, we present the research protocol and first results of a pilot cohort of 174 ME/CFS patients diagnosed at two specialized tertiary fatigue centers, including 130 (74.7%) adults (mean age 38.4; SD 12.6) and 43 (25.3%) pediatric patients (mean age 15.5; SD 4.2). A viral trigger was identified in 160/174 (92.0%) cases, with SARS-CoV-2 in almost half of them. Patients exhibited severe functional and social impairment, as reflected by a median Bell Score of 30.0 (IQR 30.0 to 40.0) and a poor health-related quality of life assessed with the Short form-36 health survey, resulting in a mean score of 40.4 (SD 20.6) for physical function and 59.1 (SD 18.8) for mental health.
The MECFS-R provides important clinical information on ME/CFS to research and healthcare institutions and, together with a multicenter ME/CFS biobank, will pave the way for research projects addressing the pathogenesis, diagnostic markers, and treatment options.
Trial registration: ClinicalTrials.gov NCT05778006.
... Another crucial aspect before prescribing exercise training is to assess for PEM (by clinical interview and if suspected by using the DePaul Symptom Questionnaire-Post-Exertional Malaise, DSQ-PEM) [54]. PEM is also the cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and therefore in long COVID cases with PEM, diagnostic ME/CFS criteria (Canadian Consensus or IOM criteria) should be checked [55,56]. If there are no signs of PEM, a "conventional" exercise training program that combines moderate to intense endurance and strength training may be used. ...
People with long COVID may suffer from a wide range of ongoing symptoms including fatigue, exertional dyspnea, reduced exercise performance, and others. In particular, impaired exercise performance is a condition that can be recovered in many people through an individualized physical exercise training program. However, clinical experience has shown that the presence of post-exertional malaise (PEM) is a significant barrier to physical exercise training in people with long COVID. Currently, there is no guideline or consensus available on how to apply exercise training in this cohort. Therefore, we conducted a literature review in the PubMed library using the following search terms: “COVID”, “post-COVID”, “long COVID” and “exercise” searching for studies from January 2020 to January 2024. Data from 46 trials were included. Exercise training regimes were very heterogeneous and none of these studies reported on the management of PEM in the context of an exercise training program. Based on the feedback from an additional survey that was answered by 14 international experts in the field of exercise training in long COVID, combined with the authors´ own extensive practical experience, a best practice proposal for exercise training recommendations has been developed. This proposal differentiates exercise procedures according to the presence of no, mild/moderate or severe PEM in people with long COVID. These recommendations may guide allied healthcare professionals worldwide in initiating and adjusting exercise training programs for people with long COVID, stratified according to the presence and severity of PEM.
... It is defined as a worsening of symptoms after daily activities that were well-tolerated before, often manifests only 12 to 48 h after activity, and can last for days or even weeks [28]. ME/CFS was documented as severe subtype of PCC in adults [29,30] and was recently reported by our pediatric group in patients with PCC younger than 18 years [31]. ME/CFS is associated with a HRQoL lower than in other chronic diseases, and significantly impairs social participation in most cases [21,22,32]. ...
... It correctly categorized adult patients with ME/CFS 81.7% of the time, while incorrectly categorizing multiple sclerosis (MS) and post-polio syndrome as ME/CFS only 16.6% of the time [73]. We have used the DSQ-PEM together with our novel Munich Berlin Symptom Questionnaire (MBSQ) to identify PEM and ME/ CFS in children, adolescents, and adults with PCC, respectively [31]. Semi-structured qualitative interviews before and after CPET in adults indicated that patients had unique PEM experiences, with differences regarding onset, severity, trajectory over time, and most bothersome symptoms [74]. ...
This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID — at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities. Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies.
Conclusion: PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions.
What is Known:
• Post-acute sequelae of coronavirus 2019 (COVID-19) (PASC) — also termed Long COVID — in children and adolescents can lead to activity limitation and reduced quality of life.
• PASC belongs to a large group of similar post-acute infection syndromes (PAIS). Specific biomarkers and causal treatment options are not yet available.
What is New:
• In February 2023, a case definition for post COVID-19 condition (PCC) in children and adolescents was provided by the World Health Organization (WHO), indicating PASC with duration of at least 2 months and limitation of daily activities. PCC can present as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
• Interdisciplinary collaborations are necessary and have been established worldwide to offer harmonized, multimodal approaches to diagnosis and management of PASC/PCC in children and adolescents.
... Some pediatric follow-up studies employed the polythetic Fukuda criteria with the addition of mandatory PEM, while others used the broader Oxford criteria, potentially including individuals without ME/CFS (4, 7, 8, 14-16, 26, 53-58). To evaluate the CCC together with the CDW-R, the PCD-J, and the IOM criteria (47), we recently developed the Munich Berlin symptom questionnaire (MBSQ) (76). The median diagnostic delay of more than one year was in line with most reports from other countries, indicating long and difficult patient journeys at any age (3,52,62,63). ...
... Quantifying frequency and severity of symptoms was recommended to increase the specificity of ME/CFS diagnosis (101), since mild symptoms are common in the general population. Our novel MBSQ can be use to quantify the severity and frequency of ME/CFS symptoms in a 5-point Likert scale (76). ...
Background
Infectious mononucleosis after primary infection with Epstein-Barr virus (EBV-IM) has been linked to the development of myalgic encephalomyelitis/chronic fatigue-syndrome (ME/CFS) in children, adolescents, and young adults. Here, we present clinical phenotypes and follow-up data from a first German cohort of young people with ME/CFS following EBV-IM.
Methods
12 adolescents and 13 young adults were diagnosed with IM-triggered ME/CFS at our specialized tertiary outpatient service by clinical criteria requiring post-exertional malaise (PEM) and a history of confirmed EBV primary infection as triggering event. Demographic information, laboratory findings, frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) were assessed and re-evaluated 6 and 12 months later.
Results
Young adults displayed more severe symptoms as well as worsening of fatigue, physical and mental functioning, and HRQoL throughout the study, compared to adolescents. After one year, 6/12 (54%) adolescents no longer met the diagnostic criteria for ME/CFS while all young adults continued to fulfill the Canadian consensus criteria. Improvement in adolescents was evident in physical functioning, symptom frequency and severity, and HRQoL, while young adults showed little improvement. EBV serology and EBV DNA load did not correlate with distinct clinical features of ME/CFS, and clinical chemistry showed no evidence of inflammation. Remarkably, the median time from symptom onset to ME/CFS diagnosis was 13.8 (IQR: 9.1–34.9) months.
Conclusions
ME/CFS following EBV-IM is a severely debilitating disease often diagnosed late and with limited responses to conventional medical care, especially in adults. Although adolescents may have a better prognosis, their condition can fluctuate and significantly impact their HRQoL. Our data emphasize that biomarkers and effective therapeutic options are also urgently needed to improve medical care and pave the way to recovery.
