Fatigue in Children and Adolescents: A Population-Based Longitudinal Study on Fatigue and Chronic Pain

Abstract:

Objective: There are limited data on the prevalence and stability of fatigue in pediatrics, particularly among youth with chronic pain. Little is known about longitudinal effects of fatigue on health outcomes such as sleep quality, psychological distress, Health-Related Quality of Life, and chronic pain.

Methods: A community-based sample of N = 1276 students (9-17 years; 52% female; 30.3% with chronic pain) from 3 schools was screened at 2 measurement points 3 months apart. Prevalence and stability of fatigue were examined. Longitudinal analyses regarding fatigue and health outcomes were run using repeated measures correlations. The impact of change in fatigue on pain progression was analyzed using multilevel linear models.

Results: In the total community sample, 4.4% reported severe fatigue symptoms. The prevalence of severe fatigue was significantly higher in students with chronic pain (11.4%) compared to those without (1.3%). Fatigue symptoms persisted for several months, worsening of symptoms was more common and improvement less common in children with chronic pain. Sleep, psychological distress, and Health-Related Quality of Life were significantly associated with fatigue across both measurement points (rs = |0.16-0.44|), with no significant differences in the strength of correlations between children with and without chronic pain (ps > .05). There was a significant interaction between change in fatigue and courses of pain intensity and functional impairment.

Conclusions: Fatigue is highly prevalent, particularly in youth with chronic pain. The negative association of fatigue with health outcomes, and its impact on the course of pain, require early identification and treatment of those affected to prevent negative long-term consequences.

Source: Sommer A, Grothus S, Claus BB, Stahlschmidt L, Wager J. Fatigue in Children and Adolescents: A Population-Based Longitudinal Study on Fatigue and Chronic Pain. J Pediatr Psychol. 2023 May 10:jsad026. doi: 10.1093/jpepsy/jsad026. Epub ahead of print. PMID: 37164626. https://pubmed.ncbi.nlm.nih.gov/37164626/

Long COVID in Children and Youth After Infection or Reinfection with the Omicron Variant: A Prospective Observational Study

Abstract:

To describe the prevalence of long COVID in children infected for the first time (n=332) or reinfected (n=243) with Omicron variant SARS-CoV-2, compared with test-negative children (n=311). 12-16% infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first-positive and reinfection (pchi-square=0.17).

Source: Pinto Pereira SM, Mensah A, Nugawela MD, Stephenson T, Ladhani SN, Dalrymple E, Dudley J, McOwat K, Simmons R, Heyman I, Segal T, Semple MG, Xu L, Shafran R; CLoCk Consortium. Long COVID in Children and Youth After Infection or Reinfection with the Omicron Variant: A Prospective Observational Study. J Pediatr. 2023 May 10:113463. doi: 10.1016/j.jpeds.2023.113463. Epub ahead of print. PMID: 37172813; PMCID: PMC10171900. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171900/ (Full text)

Lung perfusion assessment in children with long-COVID: A pilot study

Abstract:

Background: There is increasing evidence that chronic endotheliopathy can play a role in patients with Post-Covid Condition (PCC, or Long Covid) by affecting peripheral vascularization. This pilot study aimed at assessing lung perfusion in children with Long-COVID with 99m Tc-MAA SPECT/CT.

Materials and methods: lung 99m Tc-MAA SPECT/CT was performed in children with Long-COVID and a pathological cardiopulmonary exercise testing (CPET). Intravenous injections were performed on patients in the supine position immediately before the planar scan according to the EANM guidelines for lung scintigraphy in children, followed by lung SPECT/CT acquisition. Reconstructed studies were visually analyzed.

Results: Clinical and biochemical data were collected during acute infection and follow-up in 14 children (6 females, mean age: 12.6 years) fulfilling Long-COVID diagnostic criteria and complaining of chronic fatigue and postexertional malaise after mild efforts, documented by CPET. Imaging results were compared with clinical scenarios during acute infection and follow-up. Six out of 14 (42.8%) children showed perfusion defects on 99m Tc-MAA SPECT/CT scan, without morphological alterations on coregistered CT.

Conclusions: This pilot investigation confirmed previous data suggesting that a small subgroup of children can develop lung perfusion defects after severe acute respiratory syndrome coronavirus 2 infection. Larger cohort studies are needed to confirm these preliminary results, providing also a better understanding of which children may deserve this test and how to manage those with lung perfusion defects.

Source: Pizzuto DA, Buonsenso D, Morello R, De Rose C, Valentini P, Fragano A, Baldi F, Di Giuda D. Lung perfusion assessment in children with long-COVID: A pilot study. Pediatr Pulmonol. 2023 Apr 25. doi: 10.1002/ppul.26432. Epub ahead of print. PMID: 37097045. https://onlinelibrary.wiley.com/doi/10.1002/ppul.26432 (Full text)

Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people

Abstract:

Objectives: To describe the physical and mental health of children and young people (CYP) 6 months after infection with SARS-CoV-2 and explore whether this varies by COVID-19 vaccination.

Design: A non-hospitalised, national cohort of people aged 11-17 years old with PCR-confirmed SARS-CoV-2 infection and PCR negatives matched at study invitation, by age, sex, region and date of testing who completed questionnaires 6 months after PCR testing. The questionnaire included 21 symptoms and standardised scales (eg, EQ-5D-Y and Chalder Fatigue Scale).

Results: 6407 test-positive and 6542 test-negative CYP completed the 6-month questionnaire: 60.9% of test-positive vs 43.2% of test-negative CYP reported at least one symptom 6 months post-test; 27.6% of test-positive vs 15.9% of test-negative CYP reported 3+ symptoms. Common symptoms at 6 months were tiredness and shortness of breath among both test-positive and test-negative CYP; however, the prevalence of both was higher in test-positive (38.4% and 22.8%, respectively) compared with test-negative CYP (26.7% and 10.9%, respectively). 24.5% test-positive vs 17.8% test-negative CYP met the Delphi research definition of long COVID. Mental health, well-being, fatigue and health-related quality of life scores were similar among test-positive and test-negative CYP 6 months post-test. Similarly, symptomatology was similar among COVID-19-vaccinated and COVID-19-unvaccinated test-positive and test-negative CYP.

Conclusions: Six-months post-PCR testing, CYP who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but test-positive CYP had higher symptom prevalence. Mental health, well-being, fatigue and health-related quality of life were similar among test-positive and test-negative CYP, and symptoms at 6 months were similar in COVID-19 vaccinated and unvaccinated.

Source: Pinto Pereira SM, Nugawela MD, Rojas NK, Shafran R, McOwat K, Simmons R, Ford T, Heyman I, Ladhani SN, Cheung EY, Fox-Smith L, Dalrymple E, Stephenson T. Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people. Arch Dis Child. 2023 Apr;108(4):289-295. doi: 10.1136/archdischild-2022-324656. Epub 2023 Jan 4. PMID: 36599625. https://adc.bmj.com/content/108/4/289.long (Full text)

Long COVID and children’s rights

Abstract:

This policy note calls for the recognition of long COVID as a children’s rights issue in the UK. While children have been affected by school closures and lockdown restrictions throughout the pandemic, the relatively low rates of COVID-related hospitalizations and deaths among children have led to their de-prioritization in efforts to reduce the spread of the SARS-CoV-2 virus. Yet infection rates are extremely high among children in the UK, particularly secondary school students, and early studies suggest that many are not recovering for up to a year after infection.

Prolonged illness following infection, ‘long COVID’, has implications for children’s rights to education, health, and a private and family life, among others. By extension, children have a right to have their best interests taken into consideration in policy-making processes relating to long COVID. The policy note thus argues that we must recognize the significance of long COVID in children and, upon this basis, call upon the State to address its human rights implications.

Source: Vivek Bhatt, Long COVID and children’s rights, Journal of Human Rights Practice, 2023;, huac047, https://doi.org/10.1093/jhuman/huac047 (Full text)

High Prevalence of Alternative Diagnoses in Children and Adolescents with Suspected Long COVID-A Single Center Cohort Study

Abstract:

Background: Long COVID (LC) is a diagnosis that requires exclusion of alternative somatic and mental diseases. The aim of this study was to examine the prevalence of differential diagnoses in suspected pediatric LC patients and assess whether adult LC symptom clusters are applicable to pediatric patients.

Materials and methods: Pediatric presentations at the Pediatric Infectious Diseases Department of the University Hospital Essen (Germany) were assessed retrospectively. The correlation of initial symptoms and final diagnoses (LC versus other diseases or unclarified) was assessed. The sensitivity, specificity, negative and positive predictive values of adult LC symptom clusters were calculated.

Results: Of 110 patients, 32 (29%) suffered from LC, 52 (47%) were diagnosed with alternative somatic/mental diseases, and 26 (23%) remained unclarified. Combined neurological and respiratory clusters displayed a sensitivity of 0.97 (95% CI 0.91-1.00) and a negative predictive value of 0.97 (0.92-1.00) for LC.

Discussion/conclusions: The prevalence of alternative somatic and mental diseases in pediatric patients with suspected LC is high. The range of underlying diseases is wide, including chronic and potentially life-threatening conditions. Neurological and respiratory symptom clusters may help to identify patients that are unlikely to be suffering from LC.

Source: Goretzki SC, Brasseler M, Dogan B, Hühne T, Bernard D, Schönecker A, Steindor M, Gangfuß A, Della Marina A, Felderhoff-Müser U, Dohna-Schwake C, Bruns N. High Prevalence of Alternative Diagnoses in Children and Adolescents with Suspected Long COVID-A Single Center Cohort Study. Viruses. 2023 Feb 20;15(2):579. doi: 10.3390/v15020579. PMID: 36851793; PMCID: PMC9961131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961131/ (Full text)

Health system support among patients with ME/CFS in Switzerland

Abstract:

Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic and debilitating multifactorial disease. Adequate patient care is challenged by poor knowledge among health care professionals and the historical misconception that the disease is psychological in nature. This study assessed the health-related challenges faced by patients with ME/CFS in Switzerland and examined whether they receive adequate health care.

Methods: Quantitative and qualitative data were collected through a self-administered questionnaire between June and September of 2021, among 169 patients with ME/CFS in Switzerland.

Results: The mean age at diagnosis was 38.8 years. Only one-third of ME/CFS affected children and youth were correctly diagnosed before their 18th birthday. The mean time from disease onset to diagnosis was 6.7 years, and patients had an average of 11.1 different appointments and 2.6 misdiagnoses. A poor diagnosis rate and insufficient disease knowledge among health professionals in Switzerland led 13.5% of the patients to travel abroad to seek a diagnosis. Most patients (90.5%) were told at least once that their symptoms were psychosomatic. Swiss patients expressed high dissatisfaction with the health system and indicated that physicians lacked knowledge regarding ME/CFS. Therapies prescribed by physicians or tried by patients, as well as their perceived efficacy, were described. Graded Exercise Therapy (GET) was perceived as harmful by patients, whereas pacing, complementary/alternative medicine, and dietary supplements and medications to alleviate symptoms were reported to be helpful to varying degrees.

Conclusion: This study highlights that poor disease knowledge among health care providers in Switzerland has led to high patient dissatisfaction, and delays in ME/CFS diagnoses and prescription of inappropriate therapies, thus adding to patient distress and disease burden.

Source: Tschopp R, König RS, Rejmer P, Paris DH. Health system support among patients with ME/CFS in Switzerland. J Taibah Univ Med Sci. 2023 Jan 4;18(4):876-885. doi: 10.1016/j.jtumed.2022.12.019. PMID: 36852237; PMCID: PMC9957780. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957780/ (Full text)

Mental health among children with long COVID during the COVID-19 pandemic

Abstract:

A growing number of studies report that persons of all ages, infected with SARS-CoV-2, may experience long-term persistent symptoms, known as long COVID (LC) or post COVID-19 condition. This is one of the first studies examining the consequences of LC on children’s mental health. In this case-control study, we compared select mental health aspects of 103 children diagnosed with LC to a control group of 113 children uninfected with SARS-COV-2; all 4-18 years old. Both groups were assessed via parents’ questionnaires.

In comparison to the control group, children with LC exhibited more memory difficulties. However, no group differences emerged in other functional aspects (connection with friends and engagement in physical activities), problems with concentration, or levels of emotional-behavioral problems (externalizing, internalizing, ADHD, and PTSD symptoms).

We also found that children with LC had greater exposure to COVID-19-related stressors. Higher levels of parental worries regarding their children’s functioning and economic difficulties at home significantly predicted higher levels of children’s emotional-behavioral problems and were better predictors than the child’s age, social functioning, or LC diagnosis.

Conclusion: LC was associated with impairments in some aspects of children’s memory which may relate to academic functioning, but not with higher rates of emotional-behavioral problems, thus warranting interventional programs addressing school functioning and cognitive abilities in this population. Additionally, parents’ economic stress and worries regarding their child’s emotional adjustment during the pandemic, are important factors affecting pandemic-related emotional-behavioral problems among children, regardless of COVID-19 infection, that should be addressed.

What is Known:

• Children may have long COVID (LC) after being infected with SARS-COV-2.

What is New:

• LC may be associated to impairments in some aspects of children’s memory, as reported by parents.

• Parents’ economic stress and worries concerning their children’s emotional adjustment during the pandemic are associated with more distress in their children.

Source: Shachar-Lavie I, Shorer M, Segal H, Fennig S, Ashkenazi-Hoffnung L. Mental health among children with long COVID during the COVID-19 pandemic. Eur J Pediatr. 2023 Feb 14:1–9. doi: 10.1007/s00431-023-04854-z. Epub ahead of print. PMID: 36786887; PMCID: PMC9925927. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925927/ (Full text)

Computable Clinical Phenotyping of Postacute Sequelae of COVID-19 in Pediatrics Using Real-World Data

INTRODUCTION:

Since the SARS-CoV-2 pandemic began in late 2019, over 13 million children in the United States have been infected with the virus [1]. Although many of these acute infections have not resulted in severe morbidity or mortality, a subset of children and adolescents have experienced recurrent or persistent symptoms beyond the typical recovery period [2]. The constellation of findings that occur postinfection is known as postacute sequelae of SARS-CoV-2 (PASC), or colloquially as “long-Covid.” The U.S. Centers for Disease Control and Prevention (CDC) defines PASC as a wide range of health problems that linger for more than 4 weeks following an acute COVID-19 infection [3]. Although this is an area of active research, relatively little is currently known about its clinical epidemiology in the pediatric population.

Considering the large number of children who have been affected by COVID-19, it is critical that we monitor the rates, trends, and outcomes of PASC in this population. An important first step toward these efforts is the development of a tool that can quickly and easily identify cases in large clinical populations. With the widespread adoption of electronic health records (EHR), it is now possible to develop computable phenotypes using data that are collected for clinical care, which can be used for population-level analysis to inform the public health response [4, 5]. In this report, we describe a novel phenotyping algorithm to define the burden, clinical spectrum, and outcomes of pediatric PASC using real-world data.

Source: Tomini A Fashina, Christine M Miller, Elijah Paintsil, Linda M Niccolai, Cynthia Brandt, Carlos R Oliveira, Computable Clinical Phenotyping of Postacute Sequelae of COVID-19 in Pediatrics Using Real-World Data, Journal of the Pediatric Infectious Diseases Society, 2022;, piac132, https://doi.org/10.1093/jpids/piac132 https://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piac132/6957369 (Full text)

Clinical assessment of children with long COVID syndrome

Abstract:

Background: There is a need for further understanding pediatric long COVID syndrome (LCS) to be able to create specific case definitions and guidelines for providing good clinical care.

Methods: Medical records of all LCS patients who presented at our designated LC clinic were collected. We carried out descriptive analyses summarizing the history, clinical presentation, and findings of children, while doing a diagnosis of exclusion with multi-disciplinary medical examinations (physical, laboratory, and radiological examinations, specialist consultations, etc.) without a control group.

Results: Most children reported at least minor impairment to their quality of life, of which 17 (23%) had moderate or severe difficulties. Findings that could be directly connected to the linked complaint category were observed in an average of 18%, respiratory symptoms with objective alterations being the most frequent (37%). Despite our detecting mostly non-specific conditions, in a smaller number we identified well-described causes such as autoimmune thyroiditis (7%).

Conclusions: The majority of children stated an impairment in their quality of life, while symptom-related conditions were detected only in a minority. Controlled studies are needed to separate the effect of the pandemic era from the infection itself. Evidence-based pediatric guidelines could aid to rationalize the list of recommended examinations.

Impact: Long COVID syndrome is a complex entity with a great impact on children’s everyday lives. Still, there is no clear guidance for pediatric clinical management. Systematic, detailed studies with medical assessment findings could aid the process of creating evidence-based guidelines. We present validated systematic information collected during in-person medical assessments with detailed medical findings and quality of life changes. While making a diagnosis of exclusion, we could confirm symptom-related conditions only in a minority of children; however, the majority reported at least minor impairment to their quality of life.

Source: Garai R, Krivácsy P, Herczeg V, Kovács F, Tél B, Kelemen J, Máthé A, Zsáry E, Takács J, Veres DS, Szabó AJ. Clinical assessment of children with long COVID syndrome. Pediatr Res. 2022 Dec 7. doi: 10.1038/s41390-022-02378-0. Epub ahead of print. PMID: 36474113. https://www.nature.com/articles/s41390-022-02378-0 (Full text)