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This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID — at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities. Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies.     Conclusion : PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions. What is Known: • Post-acute sequelae of coronavirus 2019 (COVID-19) (PASC) — also termed Long COVID — in children and adolescents can lead to activity limitation and reduced quality of life. • PASC belongs to a large group of similar post-acute infection syndromes (PAIS). Specific biomarkers and causal treatment options are not yet available. What is New: • In February 2023, a case definition for post COVID-19 condition (PCC) in children and adolescents was provided by the World Health Organization (WHO), indicating PASC with duration of at least 2 months and limitation of daily activities.  PCC can present as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). • Interdisciplinary collaborations are necessary and have been established worldwide to offer harmonized, multimodal approaches to diagnosis and management of PASC/PCC in children and adolescents.

The lower airways harbor a community of bacterial species which is altered in asthma. We examined whether the lower airway microbiota were related to measures of asthma severity. 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. 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. 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.

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.

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.

Majority 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. Online-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. A 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%. This 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.

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. 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. Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy.

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.

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 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.