Tag: adolescents

Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents

Abstract:

SARS-CoV-2 infection causes transient cardiorespiratory and neurological disorders, and severe acute illness is rare among children. Post COVID-19 condition (PCC) may cause profound, persistent phenotypes with increasing prevalence. Its manifestation and risk factors remain elusive. In this monocentric study, we hypothesized that atopy, the tendency to produce an exaggerated immunoglobulin E (IgE) immune response, is a risk factor for the manifestation of pediatric PCC.
We present a patient cohort (n = 28) from an early pandemic period (2021–2022) with comprehensive evaluations of phenotypes, pulmonary function, and molecular investigations. PCC predominantly affected adolescents and presented with fatigue, dyspnea, and post-exertional malaise. Sensitizations to aeroallergens were found in 93% of cases.
We observed elevated IgE levels (mean 174.2 kU/L, reference < 100 kU/L) regardless of disease severity. Concurrent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) was found in 29% of patients that also faced challenges in school attendance. ME/CFS manifestation was significantly associated with elevated immunoglobulin G subclasses IgG3 (p < 0.05) and IgG4 (p < 0.05). A total of 57% of patients showed self-limiting disease courses with mean recovery at 12.7 months (range 5–25 months), 29% at 19.2 months (range 12–30 months), and the rest demonstrated overall improvement. These findings offer additional insights into immune dysregulation as a risk factor for pediatric PCC.
Source: Körner RW, Bansemir OY, Franke R, Sturm J, Dafsari HS. Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents. Children. 2023; 10(10):1598. https://doi.org/10.3390/children10101598 https://www.mdpi.com/2227-9067/10/10/1598 (Full text)

The Impact of Post-COVID-19 Syndrome in Adolescents: A Pilot Study

Abstract:

Background: Post-COVID-19 syndrome has emerged as a long-term complication in adults and children; its effect on adolescents’ performance in school is not well studied.

Objectives: To study the physical/psychological impact of prolonged post-COVID-19 symptoms on school performance.

Methods: This is a cross-sectional study using Google Forms, a web-based fully anonymized survey of children in grades 10-12.

Results: The study included 54 students with a mean age of 16 years of whom 32 had COVID-19. Two were hospitalized and 10 had symptoms lasting more than four weeks. Commonly reported chronic symptoms were fatigue and cough. Seven students quit sports; eight had a decrease in their academic performance. Adolescents being infected more than once or not being fully vaccinated were more likely to develop prolonged symptoms and quit sports while academic performance in school was not affected. Three out of 10 (30%) students who had COVID-19 and responded to the questionnaire reported not seeking help.

Conclusion: Post-COVID-19 syndrome is associated with a decline in physical but not mental performance in school. Being infected more than once with SARS-CoV-2 seems to play an important role in the persistence of post-COVID-19 symptoms despite the fact that some adolescents are hesitant to seek medical or psychological care.

Source: El Khoury J, Skoury M, El Khoury MY. The Impact of Post-COVID-19 Syndrome in Adolescents: A Pilot Study. Cureus. 2023 Jun 19;15(6):e40655. doi: 10.7759/cureus.40655. PMID: 37476124; PMCID: PMC10356177. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356177/ (Full text)

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. medRxiv 2023.07.24.23293082; doi: https://doi.org/10.1101/2023.07.24.23293082 https://www.medrxiv.org/content/10.1101/2023.07.24.23293082v1 (Full text available as PDF file)

New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection.

PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method. Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark.

It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03).

Our findings mainly obtained from US medical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.

Source: Rahmati M, Yon DK, Lee SW, Udeh R, McEVoy M, Kim MS, Gyasi RM, Oh H, López Sánchez GF, Jacob L, Li Y, Koyanagi A, Shin JI, Smith L. New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies. J Med Virol. 2023 Jun;95(6):e28833. doi: 10.1002/jmv.28833. PMID: 37264687. https://onlinelibrary.wiley.com/doi/10.1002/jmv.28833

Comparison of a 20 degree and 70 degree tilt test in adolescent myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients

Abstract:

Introduction: During a standard 70-degree head-up tilt test, 90% of adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develop an abnormal reduction in cerebral blood flow (CBF). A 70-degree test might not be tolerated by young ME/CFS patients because of the high incidence of syncopal spells. This study examined whether a test at 20 degrees would be sufficient to provoke important reductions in CBF in young ME/CFS patients.

Methods: We analyzed 83 studies of adolescent ME/CFS patients. We assessed CBF using extracranial Doppler measurements of the internal carotid and vertebral arteries supine and during the tilt. We studied 42 adolescents during a 20 degree and 41 during a 70 degree test.

Results: At 20 degrees, no patients developed postural orthostatic tachycardia (POTS), compared to 32% at 70 degrees (p = 0.0002). The CBF reduction during the 20 degree tilt of -27(6)% was slightly less than during the reduction during a 70 degree test [-31(7)%; p = 0.003]. Seventeen adolescents had CBF measurements at both 20 and 70 degrees. The CBF reduction in these patients with both a 20 and 70 degrees test was significantly larger at 70 degrees than at 20 degrees (p < 0.0001).

Conclusions: A 20 degree tilt in young ME/CFS patients resulted in a CBF reduction comparable to that in adult patients during a 70 degree test. The lower tilt angle provoked less POTS, emphasizing the importance of using the 70 degree angle for that diagnosis. Further study is needed to explore whether CBF measurements during tilt provide an improved standard for classifying orthostatic intolerance.

Source: van Campen CLMC, Rowe PC, Visser FC. Comparison of a 20 degree and 70 degree tilt test in adolescent myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients. Front Pediatr. 2023 May 12;11:1169447. doi: 10.3389/fped.2023.1169447. PMID: 37252045; PMCID: PMC10213432. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213432/ (Full text)

Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact of self-reported fatigue and illness duration

Abstract:

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS.

We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited. Lateralised whole and regional hypothalamus volumes, including the anterior superior, superior tubular, posterior, anterior inferior and inferior tubular subregions, were calculated from T1 weighted images.

When controlling for age, sex and intracranial volume, Bayesian linear regression revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a negative linear relationship between right anterior superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian ordinal regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group.

While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue and longer illness duration were associated with greater right anterior superior and superior tubular volumes, respectively. These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.

Source: Hollie Byrne, Elisha K Josev, Sarah J Knight, Adam Scheinberg, Katherine Rowe, Lionel Lubitz, Marc L Seal. Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact of self-reported fatigue and illness duration. medRxiv 2023.05.16.23290031; doi: https://doi.org/10.1101/2023.05.16.23290031 (Full text available as PDF file)

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)

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)

Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review

Abstract:

Background: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors.

Methods: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, Cochrane Library, medRxiv and bioRxiv up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness.

Results: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36% ([95% CI 15.27-32.53]). The generalized symptom (19.57%, [95% CI 9.85-31.52]) was reported most commonly, followed by respiratory (14.76%, [95% CI 7.22-24.27]), neurologic (13.51%, [95% CI 6.52-22.40]), and psychiatric (12.30%, [95% CI 5.38-21.37]). Dyspnoea (22.75%, [95% CI 9.38-39.54]), fatigue (20.22%, [95% CI 9.19-34.09]), and headache (15.88%, [95% CI 6.85-27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3-6, 6-12, and >12 months were 26.41% ([95% CI 14.33-40.59]), 20.64% ([95% CI 17.06-24.46]), and 14.89% ([95% CI 6.09-26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors.

Conclusions: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.

Source: Zheng YB, Zeng N, Yuan K, Tian SS, Yang YB, Gao N, Chen X, Zhang AY, Kondratiuk AL, Shi PP, Zhang F, Sun J, Yue JL, Lin X, Shi L, Lalvani A, Shi J, Bao YP, Lu L. Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review. J Infect Public Health. 2023 Mar 7. doi: 10.1016/j.jiph.2023.03.005. Epub ahead of print. PMCID: PMC9990879. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990879/ (Full text)