International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

Thyroid disturbances after COVID-19 and the effect of vaccination in children: a prospective tri-center registry analysis.

Rapidly evolving clinical data suggest that the novel coronavirus (SARS-CoV-2) and vaccination against COVID-19 might be associated with thyroid disturbances. However, studies remain limited among the pediatric population. Our aim was to assess the prevalence and permanence of thyroid autoimmunity (TA) and dysfunction in children after an acute infection and its potential association with vaccination. A prospective, multicenter registry analysis was performed among 458 children (mean age: 12.4 ± 3,8 years, 45.4% male) with preceding COVID-19. Patient inclusion lasted from 24th March, 2021 to 23rd March, 2022 at three pediatric outpatient facilities at Semmelweis University, Budapest. Primary outcomes were the rate of thyroid disturbances assessed by laboratory parameters (thyroid function tests, antithyroglobulin [ATG] and anti-thyroid peroxidase [ATPO] antibodies) and thyroid ultrasound. TA rate among vaccinated and unvaccinated children was determined. Children with newly diagnosed thyroid alterations were followed up for 12.7 ± 4.3 months. Six children had previous thyroid disease. Out of 452 children, 30 cases (6.6%) of newly diagnosed TA (six of them had abnormal thyroid-stimulating hormone [TSH] levels) and eight cases (1.8%) of isolated TSH elevation were observed. Ultrasound-proven autoimmune thyroiditis (AIT) was 4.0%. No association was found between COVID-19 vaccination and thyroid autoimmunity (χ2(1,N = 452) = 0.138, p = 0.815). Among children with TA, 73.3% had long-lasting alterations.  Conclusion: Vaccination had no effect on the prevalence of TA. Until further controlled studies state otherwise, children with preceding COVID-19 might benefit from thyroid screening. What is Known: • Numerous case reports implicate that coronavirus disease-2019 (COVID-19) and vaccination against SARS-CoV-2 can be responsible for thyroid disturbances. • Thyroid alterations discovered during acute COVID-19 tend to cease by time and only incidental thyroid autoimmunity (TA) is diagnosed after COVID-19. In adults, no increase in vaccine-related hyper- or hypothyroidism was found. What is New: • TA rate after COVID-19 vaccination among children was not increased. TA had no role in long COVID syndrome. • We discovered a considerable rate of TA (6.6%) and ultrasound-proven autoimmune thyroiditis (AIT) (4.0%) after SARS-CoV-2 infection, and the majority of these alterations remained positive after 6 months.

Clinical assessment of children with long COVID syndrome.

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.

The COVID-19 Pandemic Affects Seasonality, With Increasing Cases of New-Onset Type 1 Diabetes in Children, From the Worldwide SWEET Registry.

OBJECTIVE: To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally. RESEARCH DESIGN AND METHODS: We analyzed data on 17,280 cases of T1D diagnosed during 2018-2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models. RESULTS: The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.2 (95% CI 10.1-12.2) in 2018 to 21.7 (20.6-22.8) in 2021 for the youngest age-group, <6 years; from 13.1 (12.2-14.0) in 2018 to 26.7 (25.7-27.7) in 2021 for children ages 6 to <12 years; and from 12.2 (11.5-12.9) to 24.7 (24.0-25.5) for adolescents ages 12-18 years (all P < 0.001). These increases remained within the expected increase with the 95% CI of the regression line. However, in Europe and North America following the lockdown early in 2020, the typical seasonality of more cases during winter season was delayed, with a peak during the summer and autumn months. While the seasonal pattern in Europe returned to prepandemic times in 2021, this was not the case in North America. Compared with 2018-2019 (HbA1c 7.7%), higher average HbA1c levels (2020, 8.1%; 2021, 8.6%; P < 0.001) were present within the first year of T1D during the pandemic. CONCLUSIONS: The slope of the rise in pediatric new-onset T1D in SWEET centers remained unchanged during the COVID-19 pandemic, but a change in the seasonality at onset became apparent.

Anti-SARS-CoV-2 Seropositivity Among Children With Newly Diagnosed Type 1 Diabetes Mellitus: A Case-Control Study.

A sudden increase in the number of children with newly diagnosed type 1 diabetes mellitus (T1DM) was experienced during the third wave of COVID-19 epidemic in Hungary. The newly diagnosed T1DM patients had a significantly higher rate of anti-SARS-CoV-2 positivity as compared to prevalent T1DM children [OR (95% CI) 3.74 (1,08,13.55); P=0.04]. The relationship between SARS-CoV-2 infection and diabetes needs to be investigated further.

Transitional elevation of anti-tissue transglutaminase antibodies in children with type 1 diabetes mellitus without coeliac disease / A szöveti antitranszglutamináz átmeneti emelkedése coeliakiával nem társult I-es típusú cukorbeteg gyermekekben.

Összefoglaló. Bevezetés: Az 1-es típusú diabetes mellitus és a coeliakia gyakori társulása jól ismert. Néhány tanulmány beszámol átmeneti antitranszglutamináz-emelkedésrol 1-es típusú diabeteses betegekben, akiknél az emelkedett antitestszint gluténmentes diéta bevezetése nélkül normalizálódik. Célkituzés: Kutatásunk során az átmeneti antitranszglutamináz-emelkedés gyakoriságának meghatározását tuztük ki célul. További célunk volt a coeliakia gyakoriságának megállapítása 1-es típusú diabetesszel gondozott betegeink között. Módszer: A Semmelweis Egyetem I. Gyermekgyógyászati Klinikáján 1-es típusú diabetesszel gondozott betegeket vontuk be vizsgálatunkba (238 lány, 265 fiú, medián [IR] életkor az 1-es típusú diabetes diagnózisakor: 7,83 [4,67-11] év). Vizsgáltuk a jelenség idobeli megjelenését, az emelkedés mértékét, gyakoriságát és az antitest típusát. Leíró statisztikai módszereket és khi-négyzet-próbát alkalmaztunk. Eredmények: A vizsgált populációban a coeliakia gyakorisága 12,52%. Átmeneti antitranszglutamináztiter-emelkedést 48 gyermeknél (10,9%) észleltünk. Összesen 71-szer mértünk átmeneti antitranszglutamináz-emelkedést. A gyermekek közül 34 esetben (70,83%) egyszer fordult elo emelkedést mutató antitest, a többi betegnél 2-8 alkalommal. Gyakrabban tapasztaltunk izolált IgA-típusú emelkedést, mint izolált IgG-típusút (54 vs. 5). Következtetés: Az átmeneti antitranszglutamináz-emelkedés gyakorisága magas, összevetheto a valódi coeliakiás csoporttal. Kutatásunk alátámasztja a nemzetközi ajánlást, miszerint mérsékelt mértéku antitranszglutamináz-emelkedés esetén, tünetmentes 1-es típusú diabetesszel gondozott betegben a gluténfogyasztás folytatása és az antitestszintek gyakori kontrollja javasolt. Orv Hetil. 2021; 162(48): 1924-1930. INTRODUCTION: The frequent association of type 1 diabetes mellitus with coeliac disease is well known. Development of transitional elevation of anti-tissue transglutaminase antibodies in the diagnosis of type 1 diabetes is reported in some studies. In these cases, the anti-tissue transglutaminase antibodies returned to normal without gluten-free diet. OBJECTIVE: Our aim was to assess the frequency of transitional elevation of anti-tissue transglutaminase in our type 1 diabetes patients. We aimed to investigate the prevalence of coeliac disease in patients with type 1 diabetes. METHOD: Patients with type 1 diabetes at the Ist Department of Paediatrics, Semmelweis University, were enrolled in the study (238 girls, 265 boys; the median age at the time of type 1 diabetes diagnosis was 7.83 [4.67-11] years). Descriptive statistical analysis was done and the time of appearance, extent, frequency and type of elevated anti-tissue transglutaminase antibodies were examined. RESULTS: The proportion of children with diagnosed coeliac disease was 12.52%. We detected transitional anti-tissue transglutaminase elevation in 48 cases (10.9%). Temporarily elevated antibody levels were measured 71 times. In 34 children (70.83%), the temporary elevation occured once, while in the others, antibody levels became positive 2-8 times. The elevation of the IgA antibody was more frequent than the elevation of the IgG antibody (54 vs. 5). CONCLUSION: The frequency of temporary elevated anti-tissue transglutaminase levels is considered high. Our study confirms the recommendation that in the case of moderate anti-tissue transglutaminase levels with lack of clinical symptoms, control antibody measurement is necessary with ongoing gluten consumption. Orv Hetil. 2021; 162(48): 1924-1930.