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Abstract During the omicron wave of the COVID-19 pandemic and with SARS-CoV-2 vaccines becoming available, seroprevalence rates rose in children and adolescents. This study investigated the impact of both SARS-CoV-2 infections and vaccinations on the incidence of acute and prolonged symptoms in real-world conditions during the transition from the pandemic to the endemic phase. Participants from a pediatric population based seroprevalence study (CorKID study) were followed up at least two and for almost four years by survey of health status features and symptoms suggestive of post-COVID syndrome (PCS). In a subgroup (n = 259) SARS-CoV-2 antibody serology was further investigated. 789 participants of the original CorKID study cohort (n = 2.121; 37.2%) were included. 67.9% reported at least one SARS-CoV2 infection. 46.6% had received one or more SARS-CoV-2 vaccinations. In the vast majority of serologically tested participants antibodies again SARS-CoV-2 spike (98.9%) or nucleocapsid (93.3%) antigen were detected following infection and/or vaccination. At least 30% experienced one unrecognized SARS-CoV-2 infection. The overall health status was comparable between children, irrespective of SARS-CoV-2 infections and similar to pre-pandemic assessment. However, a subset of young adolescents exhibited a decline in physical performance compared to pre-pandemic conditions. After infection, PCS-like symptoms persisted in 7% of the respondents for more than three months and up to four years. SARS-CoV-2 vaccinated participants (47%) reported 12% less acute flu-like infections other than SARS-CoV-2. Nearly all participants developed SARS-CoV-2 antibodies in this longitudinal study through either vaccination or infection during the Omicron wave. About 7% of participants suffered from PCS symptoms, predominately fatigue and exhaustion. Furthermore, participants who received vaccinations against SARS-CoV-2 reported a lower frequency of acute infections during follow-up.

With the emergence of SARS-CoV-2, various non-pharmaceutical interventions were adopted to control virus transmission, including school closures. Subsequently, the introduction of vaccines mitigated not only disease severity but also the spread of SARS-CoV-2. This study leveraged an adapted SIR model and non-linear mixed-effects modeling to quantify the impact of remote learning, school holidays, the emergence of Variants of Concern (VOCs), and the role of vaccinations in controlling SARS-CoV-2 spread across 16 German federal states with an age-stratified approach. Findings highlight a significant inverse correlation (Spearman's ρ = −0.92, p

Abstract Background Primary ciliary dyskinesia (PCD) is a rare genetical disease with malfunction of the motile cilia leading to impaired muco-ciliary clearance in the respiratory tract. There is no cure for PCD, only supportive therapy aimed at minimizing the progression of the disease and improving the patient’s quality of life (QoL). Physical activity (PA) is one of these recommended supportive therapies for people with PCD (pwPCD). However, there is no scientific evidence to support this recommendation. In addition, regular medical advice to increase PA remains largely ineffective in pwPCD. Methods To test the main hypothesis, that an individualized and supported PA program leads to a better QoL 6 months after randomization (QoL-PCD questionnaire) compared to usual recommendation in pwPCD, 158 pwPCD aged 7 to 55 years are to be included in this multi-center randomized controlled trial (RCT). After the screening visit, a 1:1 randomization stratified by age group and FEV1 will be performed. A QoL-PCD questionnaire, motor test, and lung function will be carried out at regular intervals in both groups. PA is recorded in both groups using activity trackers during the study period. The main aim of the trial is to estimate the difference in the change of QoL between the groups after 6 months. Therefore, our full analysis set consists of all randomized patients and analysis is performed using the intention-to-treat principle. Statistical software R ( http://www.r-project.org ) is used. Ethical approvement without any reservations: RUB Bochum Ethics Committee (No. 23–7938; December 4, 2023). Recruitment start: March 2024. Discussion Limitations result from the rarity of PCD with its broad disease spectrum and the large age range. These are reduced by stratified randomization and the measurement of the individual change in QoL as primary endpoint. In our view, only a PA program tailored to individual needs with close contact to trainers offers the chance to meet personal needs of pwPCD and to establish PA as a pillar of therapy in the long term. The study protocol explains all procedures and methods of recruitment, implementation of the study visits and intervention, measures for patient and data safety, and for minimizing risks and bias. Trial registration German Clinical Trials Register (DRKS) 00033030. Registered on December 7, 2023. Update 10 July 2024. Study protocol version 10 Version 1.2; 12 June 2024

Background: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. Methods: Using different media, we recruited Ukrainian refugees at 13 sites between 9–12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. Results: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children.Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. Conclusions: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.

Background: Very-low-birth-weight infants (VLBWIs; birth weight < 1500 g) are at an increased risk of complicated influenza infection, which frequently includes pneumonia, encephalitis or even death. Data on influenza immunization and its outcome in VLBWIs are scarce. This study aimed to provide epidemiological data on influenza immunization for German VLBWIs and hypothesized that immunization would protect VLBWIs from infection-mediated neurodevelopmental impairment and preserves lung function at early school age. Methods: In this observational population-based German Neonatal Network (GNN) study, infants born between 2009 and 2015 were invited to partake in a 6-year follow-up investigation including lung function and developmental testing. Uni- and multivariate analyses were performed to evaluate the clinical characteristics and outcomes of influenza-immunized VLBWIs compared to non-immunized VLBWIs. Results: Influenza immunization was performed in 871 out of the 3358 VLBWIs (26%) with six-year follow-up. Immunized infants were characterized by a low gestational age and higher rates of morbidity, particularly bronchopulmonary dysplasia. Although early immunization showed no safety signals and had protective effects on the long-term risk of bronchitis (OR: 0.2; CI: 0.1–0.6; p = 0.002), most VLBWIs (88.0%) were unimmunized in their first influenza season. Conclusions: Influenza immunization was not associated with improved lung function (forced expiratory volume in one second and forced vital capacity) or a better neurocognitive outcome (intelligence quotient and strengths and difficulties questionnaire) at early school age. In Germany, only one quarter of 6-year-old VLBWIs were immunized against influenza, particularly those born

BackgroundHabitual physical activity (PA) and exercise training are accepted as important aspects of care for people with cystic fibrosis (pwCF) to improve health-related measures of physical fitness, which in turn have a positive impact on quality of life and prognosis. In the last decade, effective CFTR modulator therapies have become a promising treatment for pwCF by targeting the underlying cause of CF. This highly effective therapy improves clinical outcomes and quality of life in people with specific CFTR mutations. Little is known about the longitudinal pattern of PA or the impact of the highly effective modulator therapy with Elexacaftor/Tezacaftor/Ivacaftor (ETI) on PA in adult pwCF. This study assessed the course of device-based PA measurement in adult pwCF and evaluated the effects of ETI on habitual physical activity in those who were eligible for ETI.MethodsData from adult pwCF (aged ≥18 years) were analysed at baseline and follow-up, using identical assessments at both time points. Outcome parameters were PA in steps/day and the intensity of PA. The group that received ETI was treated for an average of 33 weeks and not for the entire duration of the period. The data were collected between 2021 and 2022, following the removal of absolute pandemic restrictions/lockdowns.ResultsFollow-up duration was 5.6 years in pwCF with ETI (ETI group, n = 21) and 6.5 years in pwCF without ETI (non-ETI group, n = 6). From baseline to follow-up, pwCF treated with ETI had a significant increase in steps/day (+25%, p = 0.019) and a non-significant increase in moderate-to-vigorous intensity time (+5.6%, p = 0.352). Conversely, individuals in the non-ETI group showed a non-significant decrease in both steps/day −3.2%, p = 0.893) and moderate-to-vigorous intensity time (−25%, p = 0.207). The ETI group showed a significant decrease in percent predicted forced expiratory volume in 1 s (ppFEV1) and FEV1 z-score before the start of ETI treatment, both of which improved significantly after therapy initiation. Body weight and body mass index also improved significantly with ETI use.ConclusionsThese data suggest that ETI treatment has a positive effect on habitual physical activity behavior in the adult pwCF studied.

Summary: Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome. Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design. From October 1, 2018 to September 30, 2019, participants were allocated to standard care (SC, N = 684), and from October 1, 2019 to January 31, 2021 to innovative care (IC, N = 695). The cohorts consisted mainly of adult participants with only a minority of children included (N = 67). IC included the involvement of a mental health specialist in all aspects of care (e.g., assessing medical records, clinic visits, telehealth care, and case conferences). Clinicaltrials.gov identifier: NCT03563677. Findings: The proportion of patients with diagnoses established within 12 months after the first visit to the CRD explaining the entire symptomatology (primary outcome) was 19% (N = 131 of 672) in the SC and 42% (N = 286 of 686) in the IC cohort (OR adjusted for centre effects 3.45 [95% CrI: 1.99–5.65]). The difference was mainly due to a higher prevalence of mental disorders and non-rare somatic diseases in the IC cohort. The median time to explaining diagnoses was one month shorter with IC (95% CrI: 1–2), and significantly more patients could be referred to local regular care in the IC (27.5%; N = 181 of 659) compared to the SC (12.3%; N = 81 of 658) cohort (OR adjusted for centre effects 2.70 [95% CrI: 2.02–3.60]). At 12-month follow-up, patient satisfaction with care was significantly higher in the IC compared to the SC cohort, while quality of life was not different between cohorts. Interpretation: Our findings suggested that including a mental health specialist in the entire evaluation process of CRDs for undiagnosed adolescents and adults should become an integral part of the assessment of individuals with a suspected rare disease. Funding: The study was funded by the Global Innovation Fund from the Joint Federal Committee in Germany (Innovationsfonds des Gemeinsamen Bundesausschusses), grant number 01NVF17031.

Summary: Background: Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF. Methods: This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months. Findings: The study included 2645 pwCF from 67 centres in Germany (mean age 28.0 ± 11.5 years). Over the first year after ETI was initiated, percent predicted forced expiratory volume in 1 s (ppFEV1) increased by 11.3% (95% confidence interval [CI] 10.8–11.8, p

Given the crucial role of vaccination in halting the COVID-19 pandemic, it is imperative to understand the factors that motivate adolescents to get vaccinated. We surveyed adolescents and their accompanying guardians scheduled to receive a COVID-19 vaccination (Comirnaty) in an urban region in Germany in mid-2021 regarding their motivation for getting vaccinated and collected data on their sociodemographic characteristics, medical history, vaccination status, and any history of COVID-19 infection in the family. We also queried information strategies related to the SARS-CoV-2 pandemic. Motivations for getting vaccinated were similar among adolescents and their parents. The primary reasons for vaccination were protection against SARS-CoV-2-related illness and gaining access to leisure facilities. This was not influenced by gender, health status, migration background, or the presence of chronic or acute diseases. The percentage of parents who had received SARS-CoV-2 immunization and the proportion of parents with a high level of education were higher among study participants than in the general population. Adolescents were especially willing to be vaccinated if they came from a better educational environment and had a high vaccination rate in the family. Emphasizing the importance of vaccination among all segments of the population and removing barriers to vaccines may lead to an ameliorated acceptance of COVID-19 vaccines.

BackgroundAvailable data on aerosol emissions among children and adolescents during spontaneous breathing are limited. Our aim was to gain insight into the role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and whether aerosol measurements among children can be used to help detect so-called superspreaders—infected individuals with extremely high numbers of exhaled aerosol particles.MethodsIn this prospective study, the aerosol concentrations of SARS-CoV-2 PCR-positive and SARS-CoV-2 PCR-negative children and adolescents (2–17 years) were investigated. All subjects were asked about their current health status and medical history. The exhaled aerosol particle counts of PCR-negative and PCR-positive subjects were measured using the Resp-Aer-Meter (Palas GmbH, Karlsruhe, Germany) and compared using linear regression.ResultsA total of 250 children and adolescents were included in this study, 105 of whom were SARS-CoV-2 positive and 145 of whom were SARS-CoV-2 negative. The median age in both groups was 9 years (IQR 7–11 years). A total of 124 (49.6%) participants were female, and 126 (50.4%) participants were male. A total of 81.9% of the SARS-CoV-2-positive group had symptoms of viral infection. The median particle count of all individuals was 79.55 particles/liter (IQR 44.55–141.15). There was a tendency for older children to exhale more particles (1–5 years: 79.54 p/L; 6–11 years: 77.96 p/L; 12–17 years: 98.63 p/L). SARS-CoV-2 PCR status was not a bivariate predictor (t = 0.82, p = 0.415) of exhaled aerosol particle count; however, SARS-CoV-2 status was shown to be a significant predictor in a multiple regression model together with age, body mass index (BMI), COVID-19 vaccination, and past SARS-CoV-2 infection (t = 2.81, p = 0.005). COVID-19 vaccination status was a highly significant predictor of exhaled aerosol particles (p

SARS-CoV-2 infection rates in children and adolescents are often underestimated due to asymptomatic or oligosymptomatic infections. Seroprevalence studies can reveal the magnitude of “silent” infections in this age group and help to assess the risk of infection for children but also their role in spreading the disease. In total, 2045 children and their parents from the Ruhr region were finally included after the exclusion of drop-outs. Seroconversion rates among children of all age groups increased from 0.5% to 8% during the study period and were about three to fourfold higher than the officially registered PCR-based infection rates. Only 41% recalled symptoms of infection; 59% were asymptomatic. In 51% of the infected children, at least one parent also developed SARS-CoV-2 antibodies. Depending on local incidences, the rates of seroconversion rose to different levels during the study period. Although the dynamics of infection within the study cohort mirrors local incidence, the figure of SARS-CoV-2 infections in children and adolescents appears to be high. Reported contact with SARS-CoV-2-infected individuals in the same household carries a high risk of infection.

BackgroundLong-term neurological complaints after SARS-CoV-2 infection occur in 4–66% of children and adolescents. Controlled studies on the integrity of the peripheral nerve system are scarce. Therefore, we examined the somatosensory function in children and adolescents after SARS-CoV-2 infection in a case-control study compared with age-matched individuals.Materials and MethodsEighty-one subjects after SARS-CoV-2 infection (n = 44 female, 11.4 ± 3.5 years, n = 75 SARS-CoV-2 seropositive, n = 6 PCR positive during infection and SARS-CoV-2 seronegative at the time point of study inclusion, n = 47 asymptomatic infection) were compared to 38 controls without SARS-CoV-2 infection (26 female, 10.3 ± 3.4 years, n = 15 with other infection within last 6 months). After standardised interviews and neurological examinations, large fibre (tactile and vibration detection thresholds) and small fibre (cold and warm detection thresholds, paradoxical heat sensation) functions were assessed on both feet following a validated protocol. After z-transformation of all values, all participants were compared to published reference values regarding the number of abnormal results. Additionally, the mean for all sensory parameters values of both study groups were compared to an ideal healthy population (with z-value 0 ± 1), as well as with each other, as previously described. Statistical analyses: t-test, Chi-squared test, and binominal test.FindingsNone of the controls, but 27 of the 81 patients (33%, p < 0.001) reported persistent complaints 2.7 ± 1.9 (0.8–8.5) months after SARS-CoV-2 infection, most often reduced exercise capacity (16%), fatigue (13%), pain (9%), or paraesthesia (6%). Reflex deficits or paresis were missing, but somatosensory profiles showed significantly increased detection thresholds for thermal (especially warm) and vibration stimuli compared to controls. Approximately 36% of the patients after SARS-CoV-2, but none of the controls revealed an abnormal sensory loss in at least one parameter (p < 0.01). Sensory loss was characterised in 26% by large and 12% by small fibre dysfunction, the latter appearing more frequently in children with prior symptomatic SARS-CoV-2 infection. Myalgia/paraesthesia was indicative of somatosensory dysfunction. In all eight re-examined children, the nerve function recovered after 2–4 months.InterpretationThis study provides evidence that in a subgroup of children and adolescents previously infected with SARS-CoV-2, regardless of their complaints, the function of large or small nerve fibres is presumably reversibly impaired.

Background: Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB4), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype.Methods: NGs from asthmatic nd healthy children were stimulated with 10 nM LTB4/100 nM N-formylmethionine-leucyl-phenylalanine and neutrophil migration was documented following our prior SiMA (simplified migration assay) workflow, capturing morphologic and dynamic parameters from single-cell tracking in the images. Demographic, clinical and serum cytokine data were determined in the ALLIANCE cohort.Results: A reduced chemotactic response towards LTB4 was confirmed in asthmatic donors regardless of inhaled corticosteroid (ICS) treatment. By contrast, only NGs from ICS-treated asthmatic children migrate similarly to controls with the exception of Th1-high donors, whose NGs presented a reduced and less directed migration towards the chemokines. ICS-treated and Th1-high asthmatic donors present an altered surface receptor profile, which partly correlates with migration.Conclusions: Neutrophil migration in vitro may be affected by ICS-therapy or a Th1-high phenotype. This may be explained by alteration of receptor expression and could be used as a tool to monitor asthma treatment.

Cardiovascular health at a young age has implications for preventing cardiovascular disease, and it is associated with improved physical and cognitive performance during the aging process. Sports are well known to prevent cardiovascular disease; however, school-based interventions have mostly been neglected. This cross-sectional study aimed to compare groups of high school students, stratified by the amount of physical activity in their high school curriculum and downtime. Comparisons concerning physical and cognitive performance and arterial stiffness were made. A total of 63 senior-year students were investigated. Arterial stiffness was assessed using the oscillometric technique with ArteriographTM detection. Three-kilometer and pendulum runs were conducted as typical training loads. Cognitive performance was evaluated via the visual and verbal memory and number connection tests. Regarding cognitive skills, extracurricular physical activity improved the number connection test in male participants (p = 0.004). For physical performance, female students with a sports-focused curriculum were faster in the 3 km run (p < 0.001). Concerning arterial stiffness, the measurements yielded a lower mean arterial pressure (p = 0.015) and aortic pulse wave velocity (p = 0.04) in male students with a sports-focused curriculum. In summary, extracurricular physical activity and enrollment in a sports-focused curriculum may be associated with lower cardiovascular risk due to lower arterial stiffness and better physical and cognitive abilities.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.

BackgroundPersistent respiratory symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults are frequent, and there can be long-term impairment of pulmonary function. To date, only preliminary evidence is available on persistent respiratory sequelae of SARS-CoV-2 in children and adolescents. Our objective was to examine the long-term effects of symptomatic and asymptomatic SARS-CoV-2 infections on pulmonary function in this age group in a single-center, controlled, prospective study.MethodsParticipants with serological or polymerase chain reaction-based evidence of SARS-CoV-2 infection were recruited from a population-based study of seroconversion rates. Multiple-breath washout (MBW), body plethysmography, and diffusion capacity testing were performed for children and adolescents. Participants were interviewed about their symptoms during the acute phase of infection and long-lasting symptoms. Cases were compared with SARS-CoV-2 seronegative controls from the same population-based study with and without history of respiratory infection within 6 months prior to assessment. Primary endpoints were differences in pulmonary function, including diffusion capacity and MBW, between participants with and without evidence of SARS-CoV-2 infection. Secondary endpoints included correlation between lung function and long-lasting symptoms as well as disease severity.FindingsIn total, 73 seropositive children and adolescents (5–18 years) were recruited after an average of 2.6 months (range 0.4–6.0) following SARS-CoV-2 infection. Among 19 patients (27.1%) who complained of persistent or newly emerged symptoms since SARS-CoV-2, 8 (11.4%) reported respiratory symptoms. No significant differences were detected in frequency of abnormal pulmonary function when comparing cases with 45 controls, including 14 (31.1%) with a history of previous infection (SARS-CoV-2: 12, 16.4%; controls: 12, 27.7%; odds ratio 0.54, 95% confidence interval 0.22–1.34). Only two patients with persistent respiratory symptoms showed abnormal pulmonary function. Multivariate analysis revealed reduced forced vital capacity (p = 0.012) in patients with severe SARS-CoV-2 infection.InterpretationPulmonary function is rarely impaired in children and adolescents after SARS-CoV-2 infection, except from those with severe infection, and did not differ between SARS-CoV-2 and other previous infections, suggesting that SARS-CoV-2 is not more likely to cause pulmonary sequelae than other infections. The discrepancy between persisting respiratory symptoms and normal pulmonary function suggests a different underlying pathology such as dysfunctional breathing.

Studies in recent years and especially since the beginning of the COVID-19 pandemic have shown a significant increase in the problematic use of computer games and social media. Adolescents having difficulties in regulating their unpleasant emotions are especially prone to Problematic Internet Use (PIU), which is why emotion dysregulation has been considered a risk factor for PIU. The aim of the present study was to assess problematic internet use (PIU) in adolescents after the third wave (nearly 1.5 years after the onset in Europe) of the COVID-19 pandemic. In the German region of Siegen-Wittgenstein, all students 12 years and older from secondary-level schools, vocational schools and universities were offered a prioritized vaccination in August 2021 with an approved vaccine against COVID-19. In this context, the participants filled out the Short Compulsive Internet Use Scale (SCIUS) and two additional items to capture a possible change in digital media usage time and regulation of negative affect due to the COVID-19 pandemic. A multiple regression analysis was performed to identify predictors of PIU. The original sample consisted of 1477 participants, and after excluding invalid cases the final sample size amounted to 1268 adolescents aged 12–17 (x = 14.37 years, SD = 1.64). The average prevalence of PIU was 43.69%. Gender, age, digital media usage time and the intensity of negative emotions during the COVID-19 pandemic were all found to be significant predictors of PIU: female gender, increasing age, longer digital media usage time and higher intensity of negative emotions during the COVID-19 pandemic were associated with higher SCIUS total scores. This study found a very high prevalence of PIU among 12- to 17-year-olds for the period after the third wave of the COVID-19 pandemic, which has increased significantly compared to pre-pandemic prevalence rates. PIU is emerging as a serious problem among young people in the pandemic. Besides gender and age, pandemic-associated time of digital media use and emotion regulation have an impact on PIU, which provides starting points for preventive interventions.

BackgroundMajority of active tuberculosis (TB) cases in children in low-incidence countries are due to rapid progression of infection (latent TB infection (LTBI)) to disease. We aimed to assess common practice for managing paediatric LTBI in Austria, Germany and Switzerland prior to the publication of the first joint national guideline for paediatric TB in 2017.MethodsOnline-based survey amongst pediatricians, practitioners and staff working in the public health sector between July and November 2017. Data analysis was conducted using IBM SPSS.ResultsA total of 191 individuals participated in the survey with 173 questionnaires included for final analysis. Twelve percent of respondents were from Austria, 60% from Germany and 28% from Switzerland. Proportion of children with LTBI and migrant background was estimated by the respondents to be >50% by 58%. Tuberculin skin test (TST) and interferon-γ-release-assay (IGRA), particularly Quantiferon-gold-test, were reported to be used in 86% and 88%, respectively. In children > 5 years with a positive TST or IGRA a chest x-ray was commonly reported to be performed (28%). Fifty-three percent reported to take a different diagnostic approach in children ≤ 5 years, mainly combining TST, IGRA and chest x-ray for initial testing (31%). Sixty-eight percent reported to prescribe isoniazid-monotherapy: for 9 (62%), or 6 months (6%), 31% reported to prescribe combination therapy of isoniazid and rifampicin. Dosing of isoniazid and rifampicin below current recommendations was reported by up to 22% of respondents. Blood-sampling before/during LTBI treatment was reported in >90% of respondents, performing a chest-X-ray at the end of treatment by 51%.ConclusionThis survey showed reported heterogeneity in the management of paediatric LTBI. Thus, regular and easily accessible educational activities and national up-to-date guidelines are key to ensure awareness and quality of care for children and adolescents with LTBI in low-incidence countries.

Evaluations after the first and second waves of the COVID-19 pandemic in Germany showed an increase in mental health problems and a reduction in health-related quality of life (HRQoL). The aim of the study was to assess those aspects after the third wave of COVID-19 in adolescents who decided to receive a vaccination. In students aged 12–17 years recruited from schools in one German region, mental health (by the strengths and difficulties questionnaire, SDQ) and HRQoL (by KIDSCREEN-10) were assessed by both a self- and parental report. Data from 1412 adolescents (mean age 14.3 years, SD = 1.64) and 908 parents were collected. The mean self-reported HRQoL was T = 53.7 (SD = 11.2), significantly higher in boys than in girls and higher in younger (12–14 years) than in older (15–17 years) adolescents. In total, 18.7% of adolescents reported clinically relevant psychological symptoms, especially peer problems (23.5%), emotional problems (17.4%), and hyperactivity (17.1%). Comparing the present data to evaluations after the first and second waves of COVID-19, adolescents rated a higher HRQoL and reported less mental health problems after the third wave. After 1.5 years of living with the pandemic, adolescents have adapted to the changes in everyday life. Further, the relaxation of restrictions, better school organization, and the prospect of the vaccination may have increased optimism, wellbeing, and contentment, leading to declining but still alarming rates of psychological symptoms.

Abstract Background Asthma and wheezing disorders in childhood and adulthood are clinically heterogeneous regarding disease presentation, natural course, and response to treatment. Deciphering common disease mechanisms in distinct subgroups requires harmonized molecular (endo-) phenotyping of both children and adult patients with asthma in a prospective, longitudinal setting. Methods The ALL Age Asthma Cohort (ALLIANCE) of the German Center for Lung Research (DZL) is a prospective, multi-center, observational cohort study with seven recruiting sites across Germany. Data are derived from four sources: (a) patient history from medical records, (b) standardized questionnaires and structured interviews, (c) telephone interviews, and (d) objective measurements. Objective measurements include amongst others lung function and quantitative assessment of airway inflammation and exhaled breath, peripheral blood, skin, nasal, pharyngeal, and nasopharyngeal swabs, nasal secretions, primary nasal epithelial cells, and induced sputum. In cases, objective measurements and biomaterial collection are performed regularly, while control subjects are only examined once at baseline. Discussion The standardized and detailed collection of epidemiological and physiological data, and the molecular deep phenotyping of a comprehensive range of biomaterials in a considerable number of study participants across all ages are the outstanding characteristics of this multi-center cohort. Despite extensive biomaterial sampling, and a recruitment strategy that also includes pre-school children as young as 6 months, attrition is low. In children 83.9%, and in adults 90.5% attended the 12-month follow-up. The earliest time-point to include cases, however, is disease manifestation. Therefore, unraveling mechanisms that drive disease onset is limited, as this question can only be answered in a population-based birth cohort. Nonetheless, ALLIANCE offers a unique, integrative and inter-disciplinary framework with a comprehensive molecular approach in a prospective and identical fashion across ages in order to identify biomarkers and predictors for distinct childhood wheeze and asthma trajectories as well as their further course during adulthood. Ultimately, this approach aims to translate its most significant findings into clinical practice, and to improve asthma transition from adolescence to adulthood. Trial registration NCT02496468 for pediatric arm, NCT02419274 for adult arm.

In the current SARS-CoV-2 pandemic, wearing a face mask is mandatory again during school lessons. There are no controlled studies in children to date indicating an effect on cognitive performance from wearing face masks. In a randomized controlled trial, we analysed the influence of face masks on cognitive performance of pupils during regular school lessons. Pupils (n = 133, fifth to seventh grade) were randomized by alternating allocation into control (with masks, n = 65) and intervention groups (without mask, n = 68). After two school lessons with (control) and without (intervention) face masks in class, all pupils performed digital tests for cognitive performance regarding attention and executive functions (switch, Corsi block-tapping, 2-back and flanker task). Overall, there were no significant differences in cognitive performance between both groups, masks vs. no masks. Wearing face masks has no significant influence on attention and executive functions of pupils and can still be recommended during school lessons.

Bronchiolitis obliterans (BO) is a rare, chronic form of obstructive lung disease, often initiated with injury of the bronchiolar epithelium followed by an inflammatory response and progressive fibrosis of small airways resulting in nonuniform luminal obliteration or narrowing. The term BO comprises a group of diseases with different underlying etiologies, courses, and characteristics. Among the better recognized inciting stimuli leading to BO are airway pathogens such as adenovirus and mycoplasma, which, in a small percentage of infected children, will result in progressive fixed airflow obstruction, an entity referred to as postinfectious bronchiolitis obliterans (PIBO). The present knowledge on BO in general is reasonably well developed, in part because of the relatively high incidence in patients who have undergone lung transplantation or bone marrow transplant recipients who have had graft-versus-host disease in the posttransplant period. The cellular and molecular pathways involved in PIBO, while assumed to be similar, have not been adequately elucidated. Since 2016, an international consortium of experts with an interest in PIBO assembles on a regular basis in Geisenheim, Germany, to discuss key areas in PIBO which include diagnostic workup, treatment strategies, and research fields.

Analysis of sweat chloride levels in cystic fibrosis (CF) patients is essential not only for diagnosis but also for the monitoring of therapeutic responses to new drugs, such as cystic fibrosis transmembrane conductance regulator (CFTR) modulators and potentiators. Using iontophoresis as the gold standard can cause complications like burns, is uncomfortable, and requires repetitive hospital visits, which can be particularly problematic during a pandemic, where distancing and hygiene requirements are increased; therefore, it is necessary to develop fast and simple measures for the diagnosis and monitoring of CF. A screen-printed, low-cost chloride sensor was developed to remotely monitor CF patients. Using potentiometric measurements, the performance of the sensor was tested. It showed good sensitivity and a detection limit of 2.7 × 10−5 mol/L, which covered more than the complete concentration range of interest for CF diagnosis. Due to its fast response of 30 s, it competes well with standard sensor systems. It also offers significantly reduced costs and can be used as a portable device. The analysis of real sweat samples from healthy subjects, as well as CF patients, demonstrates a proper distinction using the screen-printed sensor. This approach presents an attractive remote measurement alternative for fast, simple, and low-cost CF diagnosis and monitoring

Following publication of the original article [1], the author flagged aspects of the article that affected readability of some of the article’s scientific content.

BACKGROUND:The lower airways harbor a community of bacterial species which is altered in asthma. OBJECTIVES:We examined whether the lower airway microbiota were related to measures of asthma severity. METHODS:We prospectively recruited 26 severe asthma, 18 non-severe asthma and 12 healthy subjects. DNA was extracted from induced sputum and PCR amplification of the V3-V5 region of bacterial 16S rRNA gene was performed. RESULTS:We obtained 138,218 high quality sequences which were rarefied at 133 sequences/sample. Twenty OTUs had sequences ≥1% of total. There were marked differences in the distribution of Phyla between groups (P = 2.8x10-118). Bacteroidetes and Fusobacteria were reduced in non-severe and severe asthmatic groups. Proteobacteria were more common in non-severe asthmatics compared to controls (OR = 2.26; 95% CI = 1.94-2.64) and Firmicutes were increased in severe asthmatics compared to controls (OR = 2.15; 95%CI = 1.89-2.45). Streptococcal OTUs amongst the Firmicutes were associated with recent onset asthma, rhinosinusitis and sputum eosinophilia. CONCLUSIONS:Sputum microbiota in severe asthma differs from healthy controls and non-severe asthmatics, and is characterized by the presence of Streptococcus spp with eosinophilia. Whether these organisms are causative for the pathophysiology of asthma remains to be determined.

Clinical symptoms in children with pulmonary diseases are frequently non-specific. Rare diseases such as primary ciliary dyskinesia (PCD), cystic fibrosis (CF) or protracted bacterial bronchitis (PBB) can be easily missed at the general practitioner (GP).To develop and test a questionnaire-based and data mining-supported tool providing diagnostic support for selected pulmonary diseases.First, interviews with parents of affected children were conducted and analysed. These parental observations during the pre-diagnostic time formed the basis for a new questionnaire addressing the parents' view on the disease. Secondly, parents with a sick child (e.g. PCD, PBB) answered the questionnaire and a data base was set up. Finally, a computer program consisting of eight different classifiers (support vector machine (SVM), artificial neural network (ANN), fuzzy rule-based, random forest, logistic regression, linear discriminant analysis, naive Bayes and nearest neighbour) and an ensemble classifier was developed and trained to categorise any given new questionnaire and suggest a diagnosis. For estimating the diagnostic accuracy, we applied ten-fold stratified cross validation.All questionnaires of patients suffering from CF, asthma (AS), PCD, acute bronchitis (AB) and the healthy control group were correctly diagnosed by the fusion algorithm. For the pneumonia (PM) group 19/21 (90.5%) and for the PBB group 17/18 (94.4%) correct diagnoses could be reached. The program detected the correct diagnoses with an overall sensitivity of 98.8%. Receiver operating characteristics (ROC) analyses confirmed the accuracy of this diagnostic tool. Case studies highlighted the applicability of the tool in the daily work of a GP.For children with symptoms of pulmonary diseases a questionnaire-based diagnostic support tool using data mining techniques exhibited good results in arriving at diagnostic suggestions. In the hands of a doctor, this tool could be of value in arousing awareness for rare pulmonary diseases such as PCD or CF.

BACKGROUND: Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children. METHODOLOGY/PRINCIPAL FINDINGS: Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2-16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥ 10⁴ colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination. CONCLUSIONS/SIGNIFICANCE: Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy.