Management of severe ME/CFS in children and young people in the UK: a British Paediatric Surveillance Unit study

Abstract:

Objective: Severe myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) in children and young people (CYP) is a little-understood condition which significantly impacts education, development and quality of life. We used data from a population-wide surveillance study to explore the screening investigation, referral and management of suspected cases of paediatric severe ME/CFS.

Methods: A British Paediatric Surveillance Unit (BPSU) study reported cases of CYP with suspected severe ME/CFS between February 2018 and February 2019. Paediatricians reporting cases to BPSU and allied healthcare professionals in two large specialist paediatric ME/CFS centres were invited to complete questionnaires for CYP meeting the surveillance case definition. The study focused primarily on CYP with confirmed severe ME/CFS and the extent to which their care met NICE (The National Institute for Health and Care Excellence) recommendations but also considered separately those with probable or possible severe ME/CFS.

Results: This study includes a total of 92 CYP with suspected severe ME/CFS; 33 meeting criteria for severe ME/CFS and an additional 59 classified as probable or possible severe ME/CFS. For 16 possible cases, incomplete investigation to exclude alternative diagnoses prevented confirmation of a severe ME/CFS diagnosis. Only 21 of 33 (64%) confirmed severe ME/CFS cases had been referred to specialist services. The management provided varied considerably between patients and four received nothing at all. Of the management provided, the most frequent approaches were medication (67%), activity management (61%) and physiotherapy (61%). Domiciliary assessments and support, and social services referrals were received by 12% and 6% of confirmed severe cases. Similar proportions of management approaches were seen in probable/possible severe ME/CFS.

Conclusion: Full investigation is frequently incomplete in CYP with suspected severe ME/CFS and recommendations for referral and management are poorly implemented, in particular the needs of CYP who are unable to leave their home might be poorly met.

Source: Royston AP, Burge S, Idini I, Brigden A, Pike KC. Management of severe ME/CFS in children and young people in the UK: a British Paediatric Surveillance Unit study. BMJ Paediatr Open. 2024 Mar 7;8(1):e002436. doi: 10.1136/bmjpo-2023-002436. PMID: 38453418. https://bmjpaedsopen.bmj.com/content/8/1/e002436 (Full text)

Children and Young People with Long COVID—Comparing Those Seen in Post-COVID Services with a Non-Hospitalised National Cohort: A Descriptive Study

Abstract:

Background: Post-COVID services have been set up in England to treat children with ongoing symptoms of Long COVID. To date, the characteristics of children seeking treatment from these services has not been described.
Purpose: (1) to describe the characteristics of children aged 11–17 referred to the Pan-London Post-COVID service and (2) to compare characteristics of these children with those taking part in the United Kingdom’s largest research study of Long COVID in children (CLoCk).
Design: Data from 95 children seeking treatment from the Post-COVID service between May 2021 and August 2022 were included in the study. Their demographic characteristics, symptom burden and the impact of infection are described and compared to children from CLoCk.
Results: A high proportion of children from the Post-COVID service and CLoCk reported experiencing health problems prior to the pandemic. Almost all Post-COVID service children met the research Delphi definition of Long COVID (94.6%), having multiple symptoms that impacted their lives. Symptoms were notably more severe than the participants in CLoCk.
Conclusions: This study describes the characteristics of children seeking treatment for Long COVID compared to those identified in the largest longitudinal observational study to date. Post-COVID service children have more symptoms and are more severely affected by their symptoms following infection with COVID-19 than children in the CLoCk study. Research to understand predisposing factors for severity and prognostic indicators is essential to prevent this debilitating condition. Evaluation of short- and long-term outcomes of interventions by clinical services can help direct future therapy for this group.
Source: Newlands F, Goddings A-L, Juste M, Boyd H, Nugawela MD, Pinto Pereira SM, Whelan E, Whittaker E, Stephenson T, Heyman I, et al. Children and Young People with Long COVID—Comparing Those Seen in Post-COVID Services with a Non-Hospitalised National Cohort: A Descriptive Study. Children. 2023; 10(11):1750. https://doi.org/10.3390/children10111750 https://www.mdpi.com/2227-9067/10/11/1750 (Full text)

Incidence and persistence of post-COVID condition in children – a matched cohort study in Germany

Abstract:

Introduction: Long-term health effects of COVID-19 have been investigated by several large cohort studies. As most of these studies have been conducted in adults, data on the incidence and persistence of post-COVID-19 condition (PCC) among children and adolescents are still limited.
Methods: Using routine healthcare data from statutory health insurance in Germany, children and adolescents with laboratory-confirmed COVID-19 in 2020 were matched to controls (neither documented nor clinically suspected COVID-19) and followed for incident health conditions until 2021-09-30. To study PCC in children we considered selected health outcomes including malaise/fatigue (R53), dyspnea (R06.0), and cognitive dysfunction (F06.7, U51, R41), developmental delay (F80-89), adjustment disorder (F43), chronic fatigue syndrome (CFS; G93.3), and altered smell/anosmia (R43). The incidence of PCC was determined based on the lack of related diagnoses in the 12 months preceding the index quarter. For each outcome incidence rate ratios (IRR) were estimated using Poisson regression.
Results: At 3-month-follow-up, about 40% more individuals with COVID-19 suffered from at least one of the specified health conditions compared to controls. IRR were highest for smell/anosmia and CFS. IRR were generally higher among adolescents (≥12 years) than among younger children. Only a minority of PCC diagnoses persisted for 12 months within the COVID cohort. Diagnoses were more frequently persistent in the younger age group after one year.
Conclusions: Despite that long-term consequences of COVID-19 are less common and usually less severe in children, a considerable share of those diagnosed with PCC still suffered from specific symptoms 12 months after acute infection. Considering the high number of infected persons our findings suggest a relevant PCC related burden for health care even among children and adolescents.
Key messages:

• In routine healthcare data adolescents showed stronger associations between COVID-19 and post COVID-19 related ICD-10 diagnoses than children < 12 years of age.

• Serious ICD-10 diagnoses persisted for a longer time in younger children than adolescents.

Source: F Ehm, D Wende, F Loser, A Vivirito, S Menzer, M Batram, T Buschmann, G Sarganas, C Scheidt-Nave, J Schmitt, Incidence and persistence of post-COVID condition in children – a matched cohort study in Germany, European Journal of Public Health, Volume 33, Issue Supplement_2, October 2023, ckad160.095, https://doi.org/10.1093/eurpub/ckad160.095 https://academic.oup.com/eurpub/article/33/Supplement_2/ckad160.095/7327923 (Full text available as PDF file)

One-Year Follow-up of Young People with ME/CFS Following Infectious Mononucleosis by Epstein-Barr Virus

Abstract:

Background: Infectious mononucleosis, caused by the 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. Our study presents the first cohort of young individuals in Germany who were diagnosed with ME/CFS following EBV-IM.

Methods: We conducted a one-year follow-up of 25 young people diagnosed with ME/CFS at our specialized tertiary outpatient service by clinical criteria requiring post-exertional malaise and with documented EBV-IM as the triggering event. Demographic information, laboratory findings, frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) were assessed at first visit as well as 6 and 12 months later at follow-up visits.

Results: The physical functioning and HRQoL of the cohort were significantly impaired, with young adults displaying more severe symptoms, as well as worsening of fatigue, physical and mental functioning, and HRQoL throughout the study, compared to adolescents. After one year, we found that 6/12 (54%) adolescents no longer met the diagnostic criteria for ME/CFS, indicating partial remission, while all young adults continued to fulfill the Canadian consensus criteria. Improvement in children was evident in physical functioning, symptom frequency and severity, and HRQoL, while young adults had 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 in young people is a severely debilitating disease with diagnoses protracted longer than one year in many patients and only limited responses to conventional symptom-oriented medical care. Although younger children 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 for this very young age group to better manage their medical condition and pave the way to recovery.

Source: Rafael Pricoco, Paulina Meidel, Tim Hofberger, Hannah Zietemann, Yvonne Mueller, Katharina Wiehler, Kaja Michel, Johannes Paulick, Ariane Leone, Matthias Haegele, Sandra Mayer-Huber, Katrin Gerrer, Kirstin Mittelstrass, Carmen Scheibenbogen, Herbert Renz-Polster, Lorenz Mihatsch, Uta Behrends. One-Year Follow-up of Young People with ME/CFS Following Infectious Mononucleosis by Epstein-Barr Virus.

What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI

Abstract:

Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls.

Forty-eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi-analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section.

From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume.

Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain-behavior relationships that are not yet established in adolescence.

Source: Josev EK, Chen J, Seal M, Scheinberg A, Cole RC, Rowe K, Lubitz L, Knight SJ. What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI. J Neurosci Res. 2023 Jun 18. doi: 10.1002/jnr.25223. Epub ahead of print. PMID: 37331007. https://onlinelibrary.wiley.com/doi/10.1002/jnr.25223 (Full text)

Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19

Abstract:

The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach.

Mechanistic in-vitro studies, using microvasculature-on-chip devices, reveal that plasma from critically ill COVID-19 adults induces fibrinogen-dependent red blood cell aggregation that mechanically damages the microvascular glycocalyx. This mechanism appears unique to COVID-19, as plasma from non-COVID sepsis patients demonstrates greater red blood cell membrane stiffness but induces less significant alterations in overall blood rheology.

Multiomics analyses in pediatric patients with acute COVID-19 or the post-infectious multi-inflammatory syndrome in children (MIS-C) demonstrate little overlap in plasma cytokine and metabolite changes compared to adult COVID-19 patients. Instead, pediatric acute COVID-19 and MIS-C patients show alterations strongly associated with cytokine upregulation. These findings link high fibrinogen and red blood cell aggregation with endotheliopathy in adult COVID-19 patients and highlight differences in the key mediators of pathogenesis between adult and pediatric populations.

Source: Druzak, S., Iffrig, E., Roberts, B.R. et al. Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19. Nat Commun 14, 1638 (2023). https://doi.org/10.1038/s41467-023-37269-3 (Full text)

Long covid in children and adolescents

Editorial:

Risk appears low, but many questions remain

Symptoms involving almost every organ system have been reported after SARS-CoV-2 infection.123 Estimates of the prevalence of long covid (also called post-covid-19 condition, post-acute sequelae of covid-19, or chronic covid syndrome) vary considerably, partly because of confusion around the definition. The term long covid encompasses a broad range of symptoms, including objective complications of covid-19 (pulmonary fibrosis, myocardial dysfunction), mental health conditions, and more subjective, non-specific symptoms resembling those seen in post-viral chronic fatigue syndrome (myalgic encephalomyelitis). Most studies to date have substantial limitations, including small cohorts, absence of control groups, non-standardised capture of symptoms, lack of correction for pre-existing medical conditions, participant reported infection, and variation in follow-up, as well as selection, non-response, misclassification, and recall biases.4

In children and adolescents, acute covid-19 is less severe than in adults.56 Concern among many parents has therefore focused more on the potential long term effects of SARS-CoV-2 infection. Unfortunately, fewer data are available on long covid in young people compared with adults.7 The widely quoted one in seven frequency in children is based on a study with a 13% response rate.78

The linked study by Magnusson and colleagues (doi:10.1136/bmj-2021-066809) used nationwide register data from Norway to estimate the impact of covid-19 on long term healthcare use among 1.3 million children and adolescents.9 The authors identified a short term increase in primary (but not specialist) care use after covid-19 in all the studied age groups. This increase was related to respiratory and general or non-specific conditions, mostly in the four weeks after infection. The increase in primary care use persisted for up to six months among children aged 1-5 years. Notably, covid-19 in children had limited overall impact on healthcare services.

Read the rest of this article HERE.

Source: Petra Zimmermann. Long covid in children and adolescents. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o143 (Published 20 January 2022) https://www.bmj.com/content/376/bmj.o143.full (Full article)

Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts

Abstract:

OBJECTIVE: To investigate differences between young children, adolescents and adults with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

STUDY DESIGN: Comparison of clinical cohorts from 8 paediatric and 27 adult CFS/ME services in the UK and a paediatric randomised controlled trial from the Netherlands. Outcome measures include: fatigue (the UK-Chalder Fatigue Scale); Disability (the UK-SF-36 physical function subscale; the Netherlands-CHQ-CF87); school attendance, pain, anxiety and depression (the UK-Hospital Anxiety & Depression Scale, Spence Children’s Anxiety Scale; the Netherlands-Spielberger State-Trait Anxiety Inventory for Children, Children’s Depression Inventory); symptoms; time-to-assessment; and body mass index. We used multinomial regression to compare younger (aged <12 years) and older (aged 12-18 years) children with adults, and logistic regression to compare UK and Dutch adolescents.

RESULTS: Younger children had a more equal gender balance compared to adolescents and adults. Adults had more disability and fatigue, and had been ill for longer. Younger children were less likely to have cognitive symptoms (OR 0.18 (95% CI 0.13 to 0.25)) and more likely to present with a sore throat (OR 1.42 (1.07 to 1.90). Adolescents were more likely to have headaches (81.1%, OR 1.56 (1.36% to 1.80%)) and less likely to have tender lymph nodes, palpitations, dizziness, general malaise and pain, compared to adults. Adolescents were more likely to have comorbid depression (OR 1.51 (1.33 to 1.72)) and less likely to have anxiety (OR 0.46 (0.41 to 0.53)) compared to adults.

CONCLUSIONS: Paediatricians need to recognise that children with CFS/ME present differently from adults. Whether these differences reflect an underlying aetiopathology requires further investigation.

TRIAL REGISTRATION NUMBERS: FITNET trial registration numbers are ISRCTN59878666 and NCT00893438. This paper includes secondary (post-results) analysis of data from this trial, but are unrelated to trial outcomes.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

 

Source: Collin SM, Nuevo R, van de Putte EM, Nijhof SL, Crawley E. Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open. 2015 Oct 28;5(10):e008830. doi: 10.1136/bmjopen-2015-008830. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636651/ (Full article)