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Acute myocarditis has risen among paediatric patients in Italy, with 65 clinically suspected cases reported by 12 centres in 2024, 32 linked to parvovirus B19 (B19V) infection. In 11 cases, B19V was not ruled out despite a concurrent European outbreak. Twenty-nine children required intensive care; eight fatalities occurred. While effective for both severe B19V infection and myocarditis, intravenous immunoglobulins were given in only one-third of cases. These findings highlight the need for timely diagnosis, stronger surveillance, and standardised treatment protocols.

Purpose: To compare the clinical severity of Human Adenovirus (HAdV) infection with other viral diseases in a cohort of children, evaluating presentation, therapy, and outcome., Methods: We conducted a retrospective multicenter cohort study in Italian children hospitalized from January to December 2023 for respiratory symptoms. The study included children with HAdV infection presenting primarily with respiratory symptoms. Patients with isolated gastrointestinal involvement or coinfection with bacteria were excluded., Results: A total of 171 children were enrolled: 98 with HAdV infection (age 44.3 ± 37.9 months) and 73 with other viruses (age 20.4 ± 27.2 months). In the first group, 57.1% had a coinfection with one or more additional viruses. The most common symptoms were fever (89.8%), cough (73.5%) and sore throat (52%). Respiratory distress and hypoxemia were more frequent in the non-HAdV group. Children with HAdV infection demonstrated significantly higher C-reactive protein levels (50.8 ± 54.2 vs. 16.5 ± 33.8 mg/L, p < 0.001), experienced a longer duration of fever (4.9 ± 3.6 vs. 3.4 ± 2.3 days, p = 0.009) and were more likely to receive antibiotic treatment (77.6% vs. 27.4%, p < 0.001). No differences were observed in hospitalization stay, rate of complications, and ICU admission., Conclusions: Interestingly, our data suggests that HAdV-infected children exhibit a more pronounced inflammatory response despite experiencing less severe respiratory symptoms compared to other viruses. The presence of prolonged fever and a strong inflammatory response often leads to antibiotic overuse during the initial phase, when the viral etiology is yet to be confirmed. Early and accurate identification of HAdV infection is crucial to optimize treatment strategies and minimize unnecessary antibiotic use., (© 2024. The Author(s).)

Background: Recently, the development of advanced, noninvasive methods has allowed the study of respiratory function even in uncooperative infants. To date, there is still little data on the application of this technique in infants with suspected airway obstruction., The Aims of Our Study Were: - To evaluate the role of respiratory function testing (PFR) in the diagnosis and follow-up of infants with stridor - To evaluate the differences between patients with inspiratory stridor and expiratory stridor. - To evaluate the concordance between PFR and endoscopy., Methods: We enrolled infants aged < 1 year with a diagnosis of inspiratory and/or expiratory chronic stridor and a group of healthy controls. For each patient we performed PFR at diagnosis (T0) and for cases at follow-up, at 3 months (T1), 6 months (T2), 12 months (T3). At T0, all patients were classified according to a clinical score, and at follow-up, stature-ponderal growth was assessed. When clinically indicated, patients underwent bronchoscopy., Results: We enrolled 48 cases (42 diagnosed with inspiratory stridor and 6 expiratory stridor) and 26 healthy controls. At T0, patients with stridor had increased inspiratory time (p < 0.0001) and expiratory time (p < 0.001) than healthy controls and abnormal curve morphology depending on the type of stridor. At T0, patients with expiratory stridor had a reduced Peak expiratory flow (p < 0.023) and a longer expiratory time (p < 0.004) than patients with inspiratory stridor. We showed an excellent concordance between PFR and endoscopic examination (k = 0.885, p < 0.0001). At follow-up, we showed a progressive increase of the respiratory parameters in line with the growth., Conclusions: PFR could help improve the management of these patients through rapid and noninvasive diagnosis, careful monitoring, and early detection of those most at risk., (© 2024. The Author(s).)

Background: Following the pandemic restrictions, the epidemiology of respiratory syncytial virus (RSV) has changed, leading to intense hospitalization peaks., Objectives: This study, conducted at multiple sites in Italy, aimed to describe the temporal dynamics of two post-COVID-19 RSV epidemics. Additionally, the circulating RSV-A and -B lineages were characterized and compared to those found in 2018 and 2019., Study Design: Respiratory specimens and data were collected from RSV-positive patients, both inpatients, and outpatients, of all ages at three sites in north-central Italy. To analyze these samples, roughly one-sixth were sequenced in the attachment glycoprotein G gene and subjected to phylogenetic and mutational analyses, including pre-pandemic sequences from north-central Italy., Results: The first post-pandemic surge of RSV cases was quite intense, occurring from October 2021 to early January 2022. The subsequent RSV epidemic (from November 2022 to early March 2023) also had a high impact, characterized by a rise in elderly patient cases. Post-pandemic cases of RSV-A were caused by various strains present in Italy prior to COVID-19. In contrast, a distinct RSV-B lineage, which was concurrently spreading in other countries, was identified as the main cause of the surge in 2022-2023 but remained undetected in Italy before the pandemic., Conclusions: This study describes the temporal dynamics of post-pandemic RSV subgroups and uncovers a lineage of RSV-B with high genetic divergence that may have increased the impact of decreased population immunity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The term "sharenting" describes the increasingly popular habit of parents to share photos, videos, or other information regarding their children on their social profiles, through online platforms. It is highly likely that many parents are posting content about their underage children online with little knowledge of the risks associated with this practice. This study aims to investigate whether variables such as parents' age, gender, marital status, occupation and educational level influence the practice of sharing child-related content and the degree of awareness., Methods: We performed a pilot cross-sectional study, based on an anonymous questionnaire. The questionnaire was administered to parents of underage children attending the pediatric outpatient clinic of the Umberto I Hospital, Sapienza University, in Rome, Italy, by researchers, through the google forms platform; qualitative variables were generated on excel sheets and a statistical analysis was performed on SPSS Ibm-statistics using the chi-square test., Results: Two hundred twenty-eight parents of children under 18 years of age completed the questionnaire (82% mothers, 18% fathers); 98% of the respondents used social media and 75% of them published their children's related content online. Thirty-one percent of the compilers started their practice of sharenting in the first 6 months of life of their child. Our analysis showed that compared to parents who do not post online, parents who usually post online their children are significantly more likely to be partial employees or unemployed (p = 0,002), with lower educational level (p = 0,05), younger (less than 35 years of age (p = 0,01)) and have a higher number of followers (p < 0,001). Finally, 93% of the compilers were not aware of the current legislation and of the risks related to the practice of sharenting., Conclusions: Pediatricians, healthcare assistants and preventive healthcare professionals should play a central role in alerting parents and families to the risks of sharenting; the results of our study could draw their attention to the increasing practice of sharenting and make healthcare professionals active part in the protection of children., (© 2024. The Author(s).)

Background: Our aim was to hypothesize that the COVID-19 pandemic influenced the characteristics of viral bronchiolitis by comparing the last 3 epidemics with 3 pre-COVID-19 epidemics in infants hospitalized with bronchiolitis., Methods: We prospectively enrolled 637 consecutive infants (median age 3.0 ± 2.1 months, 58.5% males), hospitalized for bronchiolitis during 6 consecutive annual epidemic seasons from 2017 to 2023. All parents of the children were given a structured anamnestic questionnaire. A nasopharyngeal aspirate was tested for 15 respiratory viruses. As measures of severity, we evaluated the O 2 supplementation and the admission at the pediatric intensive care unit., Results: A total of 166 were hospitalized with bronchiolitis in 2017-2018, 97 in 2018-2019, 69 in 2019-2020, 0 in 2020-2021, 129 in 2021-2022 and 176 in 2022-2023. Taking together the 332 bronchiolitis cases hospitalized during the 3 prepandemic seasons, they peaked between December and January; after the flat curve in 2020-2021, the cases of bronchiolitis peaked in November 2021 and in December 2022. While the 2021-2022 season registered a less severe clinical presentation, O 2 supplementation and pediatric intensive care unit admissions increased in 2022-2023 with respect to the prepandemic seasons ( P < 0.001)., Conclusions: This study represents an important scientific demonstration of the impact of primary prevention measures on the epidemiology of viral infections; their fluctuations were related to the intensity of restrictive measures and to the changing trend of respiratory viruses. It is essential to predict the real temporal trend of bronchiolitis not to leave high-risk children uncovered and to guide hospitals to maintain a high level of readiness., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Since January 2024, Italy experiences a pertussis outbreak, primarily affecting neonates and unvaccinated infants at high risk of severe complications and mortality; 11 major paediatric centres noted 108 hospitalisations and three deaths by 10 May. The outbreak reflects increased circulation of Bordetella pertussis and non-adherence to immunisation recommendations during pregnancy. Public health interventions, including maternal immunisation, vaccination of infants as early as possible and post-exposure prophylaxis, are critical for reducing the burden of pertussis and preventing further mortality.

Introduction: Although neonatal breathing patterns vary after perinatal asphyxia, whether they change during therapeutic hypothermia (TH) remains unclear. We characterized breathing patterns in infants during TH for hypoxic-ischemic encephalopathy (HIE) and normothermia after rewarming., Methods: In seventeen spontaneously breathing infants receiving TH for HIE and in three who did not receive TH, we analyzed respiratory flow and esophageal pressure tracings for respiratory timing variables, pulmonary mechanics and respiratory effort. Breaths were classified as braked (inspiratory:expiratory ratio ≥1.5) and unbraked (<1.5)., Results: According to the expiratory flow shape braked breaths were chategorized into early peak expiratory flow, late peak expiratory flow, slow flow, and post-inspiratory hold flow (PiHF). The most braked breaths had lower rates, larger tidal volume but lower minute ventilation, inspiratory airway resistance and respiratory effort, except for the PiHF, which had higher resistance and respiratory effort. The braked pattern predominated during TH, but not during normothermia or in the uncooled infants., Conclusions: We speculate that during TH for HIE low respiratory rates favor neonatal braked breathing to preserve lung volume. Given the generally low respiratory effort, it seems reasonable to leave spontaneous breathing unassisted. However, if the PiHF pattern predominates, ventilatory support may be required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Papoff, Caresta, D'Agostino, Midulla, Petrarca, Giannini, Pisani and Montecchia.)

SARS-CoV-2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN-I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age-matched SARS-CoV-2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN-I (IFN-α/β/ε/ω), IFN-I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3-6 months after COVID-19. LC adolescents (12-17 years) had higher transcript levels of IFN-β, IFN-ε, and IFN-ω than HC, whereas LC children (6-11 years) had lower levels than HC. In adolescents, increased levels of IFN-α, IFN-β, and IFN-ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN-α/β mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age-related changes in the expression of transcripts involved in the IFN-I signaling pathway in children and adolescents with LC., (© 2024 Wiley‐VCH GmbH.)

The anti-COVID-19 intramuscular vaccination induces a strong systemic but a weak mucosal immune response in adults. Little is known about the mucosal immune response in children infected or vaccinated against SARS-CoV-2. We found that 28% of children had detectable salivary IgA against SARS-CoV-2 even before vaccination, suggesting that, in children, SARS-CoV-2 infection may be undiagnosed. After vaccination, only receptor-binding domain (RBD)-specific IgA1 significantly increased in the saliva. Conversely, infected children had significantly higher salivary RBD-IgA2 compared to IgA1, indicating that infection more than vaccination induces a specific mucosal immune response in children. Future efforts should focus on development of vaccine technologies that also activate mucosal immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Conti, Piano Mortari, Nenna, Pierangeli, Sorrentino, Frasca, Petrarca, Mancino, Di Mattia, Matera, Fracella, Albano, Scagnolari, Capponi, Cinicola, Carsetti and Midulla.)

Background: Bronchiolitis is an acute viral infection of the lower respiratory tract, typical of infants in their first year of life and causing hypoxia in the most serious cases. Bronchiolitis recognizes various demographic risk factors that are associated with greater clinical severity; however, no laboratory factors are yet able to correlate with the clinical severity. Neurotrophins as Brain-Derived Neurotrophic Factor (BDNF) are mediators of neuronal plasticity. BDNF is constitutively expressed in smooth muscle cells and epithelium of the lower respiratory tract, and as it is released during inflammatory conditions, serum levels may have a relevant role in the prognosis of infants with bronchiolitis., Objective: In the present pilot study, we aimed to disclose the presence of serum BDNF in infants hospitalized with bronchiolitis at discharge as a disease severity indicator., Methods and Results: Serum BDNF, measured at hospital discharge, was significantly lower in severe bronchiolitis (expressed as O 2 -supplemented infants). Furthermore, no changes were disclosed for the Tropomyosin receptor kinase B, the main BDNF receptor and neurofilament light chain, a biomarker of neuronal degeneration., Conclusion: Low serum BDNF in infants with severe bronchiolitis could be associated with a higher utilization by lung cells or with an altered production by lung cells. Therefore, further research is required to study if a decreased production or increased consumption of this biomarker is at the base of the above-mentioned findings.

Background: Acute bronchiolitis is a viral infection of the lower respiratory tract affecting infants aged under 12 months, variably presenting with respiratory distress, diffuse crackles and inflammatory wheezing. The main causative agent is Respiratory Syncytial Virus (RSV). The diagnosis is clinical and treatment mainly supportive. Despite the availability of more than 30 international guidelines, consistent management recommendations are lacking and considerable variability in patients' care persists among different providers., Objective: To review and describe current knowledge about epidemiology, physiopathology, clinic, diagnosis and management of acute bronchiolitis, with particular emphasis on updated evidence and future perspectives in terms of treatment and prevention., Methods and Results: We searched Cochrane for systematic reviews and PubMed for scientific articles published in the last 10 years, using a combination of the following search terms: "bronchiolitis", "respiratory syncytial virus", "epidemiology", "risk factors", "severity", "diagnosis", "clinic", "diagnostic imaging", "management", "asthma", "wheezing", "bronchodilator", "steroids", "hypertonic saline", "oxygen", "blood gas analysis", "HHHFNC", "rehydration", "enteral feeding", "parenteral hydration", "prevention", "vaccine" and "COVID-19 or SARS-CoV2". We accordingly performed a deep and extensive selection of the most updated and considerable literature on the matter, summarizing the most significant evidence concerning all aspects of acute bronchiolitis (epidemiology, clinic, diagnosis, management and prevention). Furthermore, we examined references and available guidelines from UK, USA, Canada, Italy and Spain. Results are extensively discussed below., Conclusion: Although acute bronchiolitis has been a widely known disease for decades, its therapeutic approach remained unchanged and essentially limited to respiratory and metabolic support. Despite the abundance of studies, there is no significant evidence concerning therapeutic alternatives (e.g. steroids, inhaled hypertonic solution), which are therefore not recommended. According to most recent data, "acute bronchiolitis" definition encompasses a plethora of different clinical entities related to each subject's genetic and immune predisposition. Therefore, future research should focus on the precise characterization of such subcategories in order to individualize therapeutic management and ensure the most appropriate evidence-based care., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Respiratory viruses represent the most frequent cause of mortality, morbidity and high healthcare costs for emergency visits and hospitalization in the pediatric age. Respiratory viruses can circulate simultaneously and can potentially infect the same host, determining different types of interactions, the so-called viral interference. The role of viral interference has assumed great importance since December 2019, when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) came on the scene. The aim of this narrative review is to present our perspective regarding research in respiratory virus interference and discuss recent advances on the topic because, following SARS-CoV-2 restrictions mitigation, we are experimenting the co-circulation of respiratory viruses along with SARS-CoV-2. This scenario is raising many concerns about possible virus-virus interactions, both positive and negative, and the clinical, diagnostic and therapeutic management of these coinfections. Moreover, we cannot rule out that also climatic conditions and social behaviours are involved. Thus, this situation can lead to different population epidemic dynamics, including changes in the age of the targeted population, disease course and severity, highlighting the need for prospective epidemiologic studies and mathematical modelling able to predict the timing and magnitude of epidemics caused by SARS-CoV-2/seasonal respiratory virus interactions in order to adjust better public health interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Matera, Manti, Petrarca, Pierangeli, Conti, Mancino, Leonardi, Midulla and Nenna.)

Objectives: To scrutinize whether the high circulation of respiratory syncytial virus (RSV) observed in 2021-2022 and 2022-2023 was due to viral diversity, we characterized RSV-A and -B strains causing bronchiolitis in Rome, before and after the COVID-19 pandemic., Methods: RSV-positive samples, prospectively collected from infants hospitalized for bronchiolitis from 2017-2018 to 2022-2023, were sequenced in the G gene; phylogenetic results and amino acid substitutions were analyzed. Subtype-specific data were compared among seasons., Results: Predominance of RSV-A and -B alternated in the pre-pandemic seasons; RSV-A dominated in 2021-2022 whereas RSV-B was predominant in 2022-2023. RSV-A sequences were ON1 genotype but quite distant from the ancestor; two divergent clades included sequences from pre- and post-pandemic seasons. Nearly all RSV-B were BA10 genotype; a divergent clade included only strains from 2021-2022 to 2022-2023. RSV-A cases had lower need of O 2 therapy and of intensive care during 2021-2022 with respect to all other seasons. RSV-B infected infants were more frequently admitted to intensive care units and needed O 2 in 2022-2023., Conclusions: The intense RSV peak in 2021-2022, driven by RSV-A phylogenetically related to pre-pandemic strains is attributable to the immune debt created by pandemic restrictions. The RSV-B genetic divergence observed in post-pandemic strains may have increased the RSV-B specific immune debt, being a possible contributor to bronchiolitis severity in 2022-2023., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GUIDO ANTONELLI reports financial support was provided by EU funding within the NextGeneration EU-MUR PNRR. ANNA TERESA PALAMARA reports financial support was provided by Italian Ministry of Health., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause a high burden of disease, particularly in children and the elderly. With the aim to add knowledge on RSV and HMPV infections in Italy, a prospective, multicenter study was conducted by eight centers of the Working Group on Respiratory Virus Infections (GLIViRe), from December 2018-April 2019. Weekly distribution and patients' demographic and clinical data were compared in 1300 RSV and 222 HMPV-positive cases. Phylogenetic analysis of the G-glycoprotein coding region was performed to characterize circulating strains. RSV positivity ranged from 6.4% in outpatients of all ages to 31.7% in hospitalized children; HMPV positivity was 4-1.2% with no age-association. RSV season peaked in February and ended in mid-April: HMPV circulation was higher when RSV decreased in early spring. RSV was more frequent in infants, whereas HMPV infected comparatively more elderly adults; despite, their clinical course was similar. RSV-B cases were two-thirds of the total and had similar clinical severity compared to RSV-A. Phylogenetic analysis showed the circulation of RSV-A ON1 variants and the predominance of RSV-B genotype BA10. HMPV genotype A2c was the prevalent one and presented insertions of different lengths in G. This first multicenter Italian report on seasonality, age-specific distribution, and clinical presentation of RSV and HMPV demonstrated their substantial disease burden in young patients but also in the elderly. These data may provide the basis for a national respiratory virus surveillance network., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aims: To evaluate the relationship between SARS-CoV-2 infection and autoimmunity in type 1 diabetes (T1D) and SARS-CoV-2 antibodies frequency at diagnosis of T1D during pandemic., Methods: The presence of T1D-specific autoimmunity was evaluated in a cohort of 99 children and adolescents without diabetes that contracted SARS-CoV-2 infection. Moreover, the frequency of IgM- and IgG-SARS-CoV-2 antibodies was evaluated in 41 newly diagnosed T1D patients not yet vaccinated against SARS-CoV-2 disease, collected during the pandemic, compared to healthy subjects (CTRL)., Results: None of the 99 patients that contracted SARS-CoV-2 infection during the pandemic period was found positive for T1D autoantibodies. The frequency of SARS-CoV-2 antibodies was not significantly different in patients newly diagnosed with T1D (12.2%), compared with CTRL (8.4%). Among SARS-CoV-2 antibody positive T1D patients, 80% were target of diabetes autoantibodies and 60% had another concomitant autoimmune disease. Among the CTRL subjects positive for SARS-CoV-2Abs (n = 10), none was found positive for T1D autoantibodies., Conclusions: The results of the present study do not confirm, at least in the short term, a role of COVID-19 as a potential trigger of T1D autoimmunity and do not provide evidence of an increased frequency of SARS-CoV-2 antibodies in newly diagnosed T1D patients in comparison with healthy population., (© 2023. The Author(s).)

Children with SARS-CoV-2 are mostly mild symptomatic, but they may develop conditions, such as persisting symptoms, that may put them at greater risk of complications. Our aim was to evaluate the frequency and the presence of risk factors for persisting COVID-19 symptoms in children. We carried out a prospective observational study of the clinical manifestation of Long COVID at the Department of Maternal Infantile Science of a tertiary University hospital in Rome. We included 697 children (0-18 years), with previous SARS-CoV-2 infection. Children and parents were asked questions regarding persistent symptoms of COVID-19. Children with symptoms 30 days after initial diagnosis were 185/697 (26.4%). Moreover, 81/697 (11.6%) patients presented symptoms 90 days after the diagnosis. Thirty-day-persisting symptoms were mostly present in children with anosmia, atopy, asthenia, and cough in the acute phase compared with the asymptomatic children 30 days after infection. After 90 days, symptoms described were mainly neurological (47/697 children, 6.7%), and headache (19/697; 2.7%) was the most frequent manifestation. In conclusion, a relatively large proportion of the patients reported persisting symptoms that seem to be related to the symptom burden and to the atopy. Ninety days after the infection, most of the children had recovered, showing that long-term effects are not frequent. Limitations of the study include the single-center design and the lack of a control group.

Background: Most evidence on the coronavirus disease 2019 (COVID-19) pandemic, has been obtained from web- or telephone-based surveys. In particular, few laboratory data, often incomplete, have been reported on the frequency of COVID-19-related serology at celiac disease (CD) diagnosis or on the effects of COVID-19 on the development of CD-specific autoimmunity., Objectives: The objective of this retrospective cross-sectional case/control study was to: (1) evaluate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in 78 children and adolescents at CD diagnosis (CD, 44 females, median age 7.4 years); (2) evaluate the frequency of IgA-anti-transglutaminase antibodies (IgA-tTGAbs) in 97 nonceliac patients (50 females, median age 9.0 years) who contracted SARS-CoV-2 infection during the pandemic (February-April 2021). As a control (CTRL) group, we analyzed 141 healthy subjects (79 females, median age 9.8 years) enrolled during the pandemic., Methods: SARS-CoV-2 IgM- and IgG-antibodies were detected by chemiluminescent microparticle immunoassays. IgA-tTGAbs were detected by a fluid-phase radioimmunoassay., Results: Six out of 78 (7.7%) CD patients tested positive for SARS-CoV-2Abs, with a frequency not significantly different from CTRL subjects (9.2%). None of the 97 nonceliac COVID-19 patients tested positive for IgA-tTG antibodies., Conclusion: These 2 distinct research approaches showed (1) similar frequencies of SARS-CoV-2 immunoreactivities in CD patients and CTRL subjects and, (2) no ability of SARS-CoV-2 to induce a CD-specific immune response, at least in the 3-4 months following SARS-CoV-2 infection., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Although impaired lung function after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been described in adults, it is unclear whether lung function might be altered in children, especially among asymptomatic or mildly symptomatic patients. In this study, we report the results of lung function testing performed after SARS-CoV-2 infection in a large pediatric population., Methods: The study included 589 patients with previous confirmed SARS-CoV-2 infection aged 0-18 years. Both symptomatic and asymptomatic patients during acute infection were enrolled in the study. A spirometry was performed in all cooperating patients., Results: The mean age of enrolled patients was 9.6 years and the mean time from infection to enrollment was 171 days. Spirometry was performed and deemed evaluable in 433 patients. No patient had reduced forced vital capacity (FVC) and only 14 patients (3.2%) had a forced expiratory volume in the First second (FEV1) < 80%. The mean spirometry values recorded were in the normal range. There were no statistically significant differences in spirometry values between patients with respiratory symptoms during infection and those without. Similarly, there were no differences in spirometry parameters according to the time elapsed between infection and enrollment., Conclusion: Lung function, according to spirometry values, does not appear to be impaired long after infection in the pediatric population. The presence of respiratory symptoms during SARS-CoV-2 infection would not represent a risk factor for impaired lung function in this cohort of patients., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Respiratory diseases caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV) are frequent causes of the hospitalization of children; nonetheless, RSV is responsible for the most severe and life-threatening illnesses. Viral infection triggers an inflammatory response, activating interferon (IFN)-mediated responses, including IFN-stimulated genes (ISG) expression with antiviral and immunomodulatory activities. In parallel, the reactive oxygen species (ROS) production activates nuclear factor erythroid 2-related factor 2 (NRF2), whose antioxidant activity can reduce inflammation by interacting with the NF-kB pathway and the IFN response. To clarify how the interplay of IFN and NRF2 may impact on clinical severity, we enrolled children hospitalized for bronchiolitis and pneumonia, and measured gene expression of type-I and III IFNs, of several ISGs, of NRF2 and antioxidant-related genes, i.e., glucose-6-phosphate dehydrogenase (G6PD), heme oxygenase 1 (HO1), and NAD(P)H dehydrogenase [Quinone] 1 (NQO1) in RSV- (RSV-A N = 33 and RSV-B N = 30) and HRV (N = 22)-positive respiratory samples. NRF2 and HO1 expression is significantly elevated in children with HRV infection compared to RSV ( p = 0.012 and p = 0.007, respectively), whereas ISG15 and ISG56 expression is higher in RSV-infected children ( p = 0.016 and p = 0.049, respectively). Children admitted to a pediatric intensive care unit (PICU) had reduced NRF2 expression ( p = 0.002). These data suggest, for the first time, that lower activation of the NRF2 antioxidant response in RSV-infected infants may contribute to bronchiolitis severity.

Introduction: There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy., Methods: A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis, and treatment), and sent to all the Italian PCD Centers., Results: Questionnaires obtained from 20/22 centers in 12/20 regions showed that the total number of PCD patients treated at the participating centers was of 416. Out of all centers, 55% follow <20 patients, two centers have >40 patients, and 75% follow both pediatric and adults. Age at diagnosis was between 4 and 8 years in 45% of the centers, <3 years in three centers. Nasal nitric oxide, transmission electron microscopy and ciliary high-speed video microscopy are performed in 75%, 90%, and 40% of centers, respectively. Immunofluorescence is available in five centers. Genetic analysis is offered in 55% of the centers, and in seven centers >50% of the patients have a known genetic profile. Patients treated at all centers receive inhaled saline solutions, corticosteroids and chest physiotherapy. Prophylactic antibiotics and mucolytics are prescribed in 95% and 50% of the centers, respectively. Pseudomonas infection is treated with oral or inhaled antibiotics., Conclusions: Many Italian centers care for a small number of pediatric and adult patients, and diagnosis is often delayed. We found a great variability in the available diagnostic procedures, as well in the prescribed therapies. Our study will help to uniform diagnostic algorithm and share treatments protocols for PCD in Italy and allowed to set specific national goals., (© 2023 Wiley Periodicals LLC.)

SARS-CoV-2 mRNA vaccines prevent severe COVID-19 by generating immune memory, comprising specific antibodies and memory B and T cells. Although children are at low risk of severe COVID-19, the spreading of highly transmissible variants has led to increasing in COVID-19 cases and hospitalizations also in the youngest, but vaccine coverage remains low. Immunogenicity to mRNA vaccines has not been extensively studied in children 5 to 11 years old. In particular, cellular immunity to the wild-type strain (Wuhan) and the cross-reactive response to the Omicron variant of concern has not been investigated. We assessed the humoral and cellular immune response to the SARS-CoV-2 BNT162b2 vaccine in 27 healthy children. We demonstrated that vaccination induced a potent humoral and cellular immune response in all vaccinees. By using spike-specific memory B cells as a measurable imprint of a previous infection, we found that 50% of the children had signs of a past, undiagnosed infection before vaccination. Children with pre-existent immune memory generated significantly increased levels of specific antibodies, and memory T and B cells, directed against not only the wild type virus but also the omicron variant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cinicola, Piano Mortari, Zicari, Agrati, Bordoni, Albano, Fedele, Schiavoni, Leone, Fiore, Capponi, Conti, Petrarca, Stefanelli, Spalice, Midulla, Palamara, Quinti, Locatelli and Carsetti.)

The recently discovered truncated, non-functional, ACE2 transcript (dACE2), but not the full-length ACE2 (f-lACE2), is induced by IFNs in differentiated airway cells. We measured expression of both ACE2 isoforms in SARS-CoV-2 positive and negative subjects, in relation to Interferon-stimulated genes. A significant activation of dACE2 transcript was found, in SARS-CoV-2 positive adults either hospitalized or not, showing a positive correlation with ISG15; f-lACE2 expression was weakly activated and not ISG-related. We confirmed a specific activation of dACE2 transcript in nasopharyngeal cells, related to the mucosal IFN response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: In the era of data-driven decision-making, unacceptable haziness, and inconsistency surrounds the yearlong scientific and public debate on the school closure policy in the coronavirus disease-2019 (COVID-19) pandemic mitigation efforts., Aim: The present literature review stems out of the need for a clear scaffold collecting in one place all current evidence, as well as helping to organize incoming future evidence, concerning both the role of schools in driving the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community spread and the cost-effectiveness of school closure in containing such spread., Methods: References for this review were initially identified through searches of PubMed, Scopus, and Cochrane Library for articles published from March 2020 to March 2021 by the use of key terms "Schools," "COVID-19," "pandemic," "clusters," "outbreak," and "seroprevalence," selecting all articles from 2020 to 2021 with full-text availability. A further search was undertaken by screening citations of articles found in the original search and through Google Scholar and ResearchGate., Results: Overall, evidence shows that opening schools and keeping them open in the context of the SARS-CoV-2 pandemic is possible, although behaviorally challenging and unfeasible if educational facilities or testing services are inadequate. Contrary to other respiratory viruses, children are not chief targets of SARS-CoV-2 infection, transmission, and disease. It also appears that the second wave of the SARS-CoV-2 virus spread in the WHO European region has been unrelated to school re-opening., Conclusions: A fact-based understanding of what is currently known on such a consequential policy is required to provide a basis of evidence for advocacy of either school closure or school opening at times of high-intensity community transmission of SARS-CoV-2., (© 2021 Wiley Periodicals LLC.)

Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS-CoV-2 response upon infection. To further characterize age-related differences, we studied type I and III interferon (IFN) response in SARS-CoV-2 infected and non-infected individuals of different ages. Specifically, levels of expression of type I (IFN-α, -β, -ε and -ω), type III (IFN-λ1, -λ2 and -λ3) IFNs and of the IFN-stimulated genes, ISG15 and ISG56 were quantified in nasopharyngeal cells from diagnostic swabs. Basal transcription of type I/III IFN genes was highest among children and decreased with age. Among SARS-CoV-2-infected individuals, only IFN-ε and -ω levels were significantly higher in children and young adults whereas ISGs were overexpressed in infected adults. The occurrence of symptoms in children and the need for hospitalization in adults were associated to higher transcription of several IFN genes. Starting from a pre-activated transcription level, the expression of type I and III IFNs was not highly up-regulated in children upon SARS-CoV-2 infection; young adults activated IFNs' transcription at intermediate levels whereas older adults were characterized by higher ISGs and lower IFN-ε and -ω relative expression levels. Overall, our findings contribute to recognize components of a protective IFN response as a function of age, in the context of SARS-CoV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pierangeli, Gentile, Oliveto, Frasca, Sorrentino, Matera, Nenna, Viscido, Fracella, Petrarca, D’Ettorre, Ceccarelli, Midulla, Antonelli and Scagnolari.)

Aim: Emergency room admissions have decreased globally during the COVID-19 pandemic, particularly for respiratory diseases. We evaluated hospital admissions for respiratory diseases in the first year of the Italian pandemic and compared them with the corresponding period in 2016-2017., Methods: The study was carried out at the Sapienza University in Rome, Italy, and covered 9 March to 28 February 2020-2021 and 2016-2017. We tested 85 hospitalised children who were negative for the virus that causes COVID-19 in 2020-2021 and compared them with 476 hospitalised children from 2016-2017, as we had also tested nasal washing samples for 14 respiratory viruses during that period., Results: Hospitalisations for acute respiratory tract infections were 82.2% lower in 2020-2021 than 2016-2017. The respiratory syncytial virus (RSV) and several other viruses were detected less frequently during the pandemic. An extraordinary finding was that rhinoviruses remained seasonal. In 2020-2021, we detected a virus in 54.1% of the hospitalised children: rhinoviruses in 41, RSV in 4 and other viruses in 1. This was significantly lower than the 71.6% in 2016-2017: RSV in 130, rhinoviruses in 128 and other viruses in 83., Conclusion: Pandemic measures dramatically reduced childhood respiratory infections, particularly RSV, but were less effective at reducing rhinoviruses., (©2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Bronchiolitis is the most frequent cause of hospitalization in infants younger than 1 year of age. We sought to evaluate the correlation between lymphocyte count and clinical manifestation in infants hospitalized with bronchiolitis., Materials and Methods: We performed a retrospective cohort study evaluating 1297 children hospitalized for bronchiolitis from 2004 to 2019. A nasal washing was tested for 14 respiratory viruses by PCR. A clinical severity score, ranging 0-8, was assigned at hospital admission. History and clinical course were recorded for each infant. Patients were divided in 3 groups according to lymphocyte count tertiles. Parents of enrolled patients have been phoned annually over 5 years to evaluate respiratory sequelae., Results: A total of 433 children had 2914.2 ± 745.5/mm 3 lymphocytes (Group 1), 432 had 4897.6 ± 561.5/mm 3 lymphocytes (Group 2) and 432 had 7884 ± 1903.3/mm 3 lymphocytes (Group 3). Group 1 patients were more frequently infected by RSV and presented with fever, a worse clinical severity score. They more frequently needed oxygen supplementation, underwent a prolonged hospitalization needed to be admitted to pediatric intensive care unit. Finally, they had more frequently a family history of eczema, wheezing and asthma. We found no differences between lymphocytes count and respiratory sequelae (at least two episodes of wheezing per year)., Conclusions: Infants with low lymphocyte count are more likely to have a worse clinical course of bronchiolitis., (© 2022 Wiley Periodicals LLC.)

The use of electronic cigarettes (e-cigarette) and vaping devices started as a potential aid for cessation and reducing the harmful consequences of cigarette smoking, mainly in the adult population. Today e-cigarette use is highly increasing in vulnerable populations, especially young and pregnant women, due to the misconception of its harmless use.Despite the growing acknowledgment in e-cigarette as a potential harmful device, and due to mixed information found concerning its beneficial aid for smokers, along with an insufficient clinical study done in human models, it is important to further evaluate the possible benefits and risks of non-combusting, vaping nicotine or non-nicotine delivery devices.In this review we tried to summarize the latest updated information found in the literature, concentrating mainly in the variety of adverse effects of e-cigarette use and its contribution for recent and future health concerns., (© 2022. The Author(s).)

Objective: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, a novel syndrome known as a multisystem inflammatory syndrome in children (MIS-C) was reported in previously healthy children. A possible pro-inflammatory molecule, high-mobility group box 1 (HMGB1), may be assumed to play an important role in the pathogenesis and clinical presentation of MIS-C. We described the clinical picture of patients with MIS-C and we also aimed to test and compare HMGB1 serum levels of MIS-C patients with those of patients with previous SARS-CoV2 infection and healthy children., Study Design: We determined HMGB1 levels by Western blot in 46 patients and divided them into three groups, namely, five patients with MIS-C (median age: 8.36 years), 20 children with a history of SARS-CoV-2 infection (median age: 10.45 years), and 21 healthy children (controls) (median age: 4.84 years), without evidence of respiratory infection in the last 3 months., Results: The median level of HMGB1 in the serum of five patients with MIS-C was found to be significantly higher compared with both patients with a recent history of COVID-19 (1,151.38 vs. 545.90 densitometric units (DU), p = 0.001) and control (1,151.38 vs. 320.33 DU, p = 0.001) groups. The HMGB1 level in MIS-C patients with coronary involvement had a slightly higher value with respect to patients without coronary dilatation (1,225.36 vs. 1,030.49 DU, p = 0.248). In two of the five children with MIS-C that performed a follow-up, the HMGB1 value decreased to levels that were superimposable to the ones of the control group., Conclusion: The significantly high level of HMGB1 protein found in the serum of COVID-19 and patients with MIS-C supports its involvement in inflammatory manifestations, suggesting HMGB1 as a potential biomarker and therapeutic target in patients with severe illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Petrarca, Manganelli, Nenna, Frassanito, Ben David, Mancino, Garofalo, Sorice, Misasi and Midulla.)

Introduction: Viral bronchiolitis is a common lower respiratory tract infection in infants. Environmental and genetic factors can favor respiratory tract infections., Aim: The aim of this study is to analyze risk factors for bronchiolitis and to investigate the predisposing factors for developing transient wheezing and asthma through a 6-year follow-up after hospitalization for bronchiolitis compared with a group of healthy controls that belonged to Piccolipiù cohort, who never had bronchiolitis., Methods: We enrolled 645 infants hospitalized with bronchiolitis. A structured questionnaire was used to obtain demographic and clinical data. At 6 years of age, 370 cases and 183 controls were investigated for the presence of asthma by the structured questionnaire, for prick test and for spirometry, and were classified to asthmatic, transient wheezing, and no wheezing/no asthma., Results: Breastfeeding was an independent protective factor (odds ratio [OR]: 0.3, 95% confidence interval [95% CI]: 0.2-0.4, p < 0.001) and tobacco smoke was a risk factor for the development of bronchiolitis (OR: 2.1, 95% CI: 1.4-3.1, p < 0.001). Analyzing follow-up, bronchiolitis increased the risk of developing transient wheezing by 12.9 (95% CI: 6.3-26.1, p < 0.001) and of developing asthma by 4.6 (95% CI: 1.9-10.7, p < 0.001). A positive family history of atopy increased the risk of developing asthma by 3.1 (95% CI: 1.4-6.7, p = 0.005). Asthmatic patients had a lower % FEV1, a lower % flow-volume curve (FVC), and a lower FEV1/FVC value, and they had more frequently positive skin prick test., Conclusion: Bronchiolitis is influenced by environmental factors: tobacco smoke increases its risk and breastfeeding is a protective factor. At the end of 6 years of follow-up, bronchiolitis is a significant risk factor to have pre-school wheezing and asthma., (© 2021 Wiley Periodicals LLC.)

Background: The heterogeneity of bronchiolitis may imply or reflect a different predisposition to respiratory sequelae., Objective: Our aim was to investigate whether, among infants hospitalized with bronchiolitis, different clinical profiles extracted by latent class analysis (LCA) are associated with different risks of wheezing., Methods: Over 15 consecutive epidemic seasons (2004-2019), we prospectively enrolled infants <1 year hospitalized for the first episode of bronchiolitis in a single tertiary hospital. A detailed clinical questionnaire was filled for each infant. LCA was applied to differentiate bronchiolitis phenotypes, and after hospital discharge, a phone interview was performed annually to record the presence of wheezing episodes. Adjusted multivariate regression analyses were run to investigate the risk of wheezing during 7 years follow-up according to clinical phenotypes., Results: LCA performed on 1312 infants resulted in a three-class model. Profile 1 (65.5%): moderate bronchiolitis; Profile 2 (6.1%): severe bronchiolitis; and Profile 3(28.4%): bronchiolitis infants with high eosinophils blood count. At 1 year of follow up, about 50% of children presented wheezing in each profile. Compared to Profile 1, the adjusted odds ratio (OR) of having wheezing episodes was significantly higher in Profile 2 at 2, 3, and 4 years of follow-up. At 7 years, Profile 3 had an adjusted OR = 2.58, higher than Profile 2 (adjusted OR = 2.29)., Conclusions: LCA clearly identified a "moderate", "severe," and "high eosinophils blood count" bronchiolitis. During the first 4 years after bronchiolitis, the "severe" profile showed the higher risk of wheezing, but after 7 years this risk seems higher in the "high eosinophils blood count" group., (© 2021 Wiley Periodicals LLC.)

Lung ultrasound has become increasingly used in both adult and pediatric populations, allowing the rapid evaluation of many lung and pleura diseases. This popularity is due to several advantages of the method such as the low cost, rapidity, lack of ionizing radiation, availability of bedside and repeatability of the method. These features are even more important after the outbreak of the SARS-CoV-2 pandemic, given the possibility of recognizing through ultrasound the signs of interstitial lung syndrome typical of pneumonia caused by the virus. The purpose of this paper is to review the available evidence of lung ultrasound (LUS) in children and its main applications in pediatric diseases.

Background: Community-acquired pneumonia (CAP) represents one of the most common infectious diseases among children. Diagnosis of CAP is mainly clinical. Chest X-ray (CXR) remains the gold standard for the diagnosis in severe or controversial conditions. Recently, some authors have focused on the application of ultrasound in lung diseases but the role of lung ultrasound (LUS) in the diagnosis of CAP is still debated. We aimed to study the concordance between LUS and CXR in evaluating specific signs of CAP. As a secondary aim, we sought to determine the sensitivity and specificity of LUS in CAP diagnosis compared with CXR. Finally, we evaluated the role of LUS during the follow up., Methods: We enrolled 68 children (<16 years old) hospitalized from October 2018 to September 2019 with a clinical and radiological diagnosis of CAP (cases: N = 41), or with no respiratory diseases (controls: N = 27), in whom a CXR was performed for clinical indications. All the children underwent LUS during hospitalization. The average time needed to perform LUS was 5-10 min for each child, and 19/41 cases were re-evaluated by LUS and CXR 30 days after discharge., Results: Lung ultrasound confirmed CAP diagnosis in 40/41 patients. Concordance between the two techniques was K = 0.88 for the right lung and K = 0.70 for the left lung. Lung ultrasound showed a sensitivity of 97% and a specificity of 96% compared with CXR. At the follow up, sensitivity increased to 100% while specificity was 94%., Conclusions: Our study showed a potential benefit of LUS compared with CXR in the diagnosis and the follow up of CAP., (© 2020 Japan Pediatric Society.)

In vitro interferon (IFN)α treatment of primary human upper airway basal cells has been shown to drive ACE2 expression, the receptor of SARS-CoV-2. The protease furin is also involved in mediating SARS-CoV-2 and other viral infections, although its association with early IFN response has not been evaluated yet. In order to assess the in vivo relationship between ACE2 and furin expression and the IFN response in nasopharyngeal cells, we first examined ACE2 and furin levels and their correlation with the well-known marker of IFNs' activation, ISG15, in children (n = 59) and adults (n = 48), during respiratory diseases not caused by SARS-CoV-2. A strong positive correlation was found between ACE2 expression, but not of furin, and ISG15 in all patients analyzed. In addition, type I and III IFN stimulation experiments were performed to examine the IFN-mediated activation of ACE2 isoforms (full-length and truncated) and furin in epithelial cell lines. Following all the IFNs treatments, only the truncated ACE2 levels, were upregulated significantly in the A549 and Calu3 cells, in particular by type I IFNs. If confirmed in vivo following IFNs' activation, the induction of the truncated ACE2 isoform only would not enhance the risk of SARS-CoV-2 infection in the respiratory tract., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Bronchiolitis is the most common acute viral infection of the lower respiratory tract in infants. Clinical severity is associated with different risk factors; however, no clinical, laboratory, or radiological findings are able to predict the course of the disease in full-term infants. Lung ultrasound (LUS) is a valid technique for the diagnosis and evaluation of pediatric respiratory diseases., Aims: The aim of our study was to correlate an LUS score with a clinical score, to describe lung ultrasound findings in cases and controls, and to compare LUS findings with chest X-ray (CXR) in infants hospitalized with bronchiolitis., Methods: We conducted a single-center, longitudinal, prospective study on 92 infants. Sixty-three out of 92 infants were hospitalized for acute bronchiolitis (cases) and twenty-nine out of 92 for diseases not involving the respiratory system (controls). All patients with bronchiolitis underwent a clinical evaluation with the assignment of a clinical severity score and performed lung ultrasound with the assignment of an LUS score. Twenty-three out of 63 infants with bronchiolitis underwent also a CXR for clinical indications. Control infants performed only LUS., Results: In infants with bronchiolitis LUS score showed a positive correlation with the clinical score (r = .62, p < .001) and the length of hospitalization (r = .42; p < .001). The need of oxygen therapy was more frequent in the patients with higher LUS score (p < .001). LUS findings observed in the cases were the presence of B-lines, subpleural consolidations, and abnormalities of the pleural line. No LUS alterations were observed in the controls. In patients who performed LUS and CXR, we found a correlation between the presence of abnormalities of the pleural line with LUS and the presence of air trapping with CXR (r = .55; p = .007)., (© 2020 Wiley Periodicals LLC.)

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe. Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting β2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination. Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic. We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching., Competing Interests: Conflict of interest: N.M. Liu has nothing to disclose. Conflict of interest: K.C.L. Carlsen has nothing to disclose. Conflict of interest: S. Cunningham has nothing to disclose. Conflict of interest: G. Fenu reports advisory board fees from GSK, clinical trial sponsorship from Sanofi, expenses for congresses and meetings from Novartis, personal fees for teaching a course from Chiesi, and expenses for congresses and meetings from Lusofarmaco, outside the submitted work. Conflict of interest: L.J. Fleming reports grants from Asthma UK, and fees for expert consultation and speakers fees from AstraZeneca, GSK, Novartis, Teva, Bohringer Ingelheim, Respiri and Sanofi paid direct to her institution and outside of the submitted work Conflict of interest: M. Gappa reports that she has received honoraria for lectures and/or consultancy from Boehringer Ingelheim, GSK, Novartis and Sanofi. She believes that this has not influenced any of the submitted work. Conflict of interest: B. Karadag reports for the multicentre, phase III dupilumab study EFC14153 from Sanofi, outside the submitted work. Conflict of interest: F. Midulla has nothing to disclose. Conflict of interest: L. Petrarca has nothing to disclose. Conflict of interest: M.W.H. Pijnenburg reports a consultancy fee paid to her department by Sanofi Genzyme during the conduct of the study. Conflict of interest: T. Reier-Nilsen has nothing to disclose. Conflict of interest: N.W. Rutjes has nothing to disclose. Conflict of interest: F. Rusconi has nothing to disclose. Conflict of interest: J. Grigg reports personal fees for asthma advisory boards from AstraZeneca and GSK, personal fees for a continuing professional development lecture from Novartis, and personal fees for an asthma advisory board from Vifor Pharma, outside the submitted work., (Copyright ©ERS 2020.)

In this article, the Group Chairs and the Early Career Members of the Paediatric Assembly of the European Respiratory Society (ERS) highlight some of the most interesting findings in the field of paediatrics presented at the 2019 ERS International Congress, which was held in Madrid, Spain. The main findings from each group are summarised at the end of each chapter., Competing Interests: Conflict of interest: R. Nenna has nothing to disclose. Conflict of interest: M. Slaats has nothing to disclose. Conflict of interest: R. Ersu has nothing to disclose. Conflict of interest: D. Lo has nothing to disclose. Conflict of interest: S. Saglani has nothing to disclose. Conflict of interest: C. Nissenbaum has nothing to disclose. Conflict of interest: A.R. Horsley reports grants from the NIHR, the Cystic Fibrosis Foundation and the Cystic Fibrosis Trust, and personal fees from Vertex Pharmaceuticals and Mylan, outside the submitted work. Conflict of interest: M. Proesmans has nothing to disclose. Conflict of interest: L. Petrarca has nothing to disclose. Conflict of interest: E. Williams has nothing to disclose. Conflict of interest: T. Dassios has nothing to disclose. Conflict of interest: C. Ardura-Garcia has nothing to disclose. Conflict of interest: L. Duijts reports a speaker fee for the 2019 International Congress and meeting fees for the Task Force on Bronchopulmonary Dysplasia (TF 2015-18) from the European Respiratory Society writing of the manuscript. Conflict of interest: H. Marczak has nothing to disclose. Conflict of interest: D. Snijders reports a grant for networking (no payment fee) from COST Action CA16125 outside the submitted work. Conflict of interest: R. Rottier has nothing to disclose. Conflict of interest: C-M. Chao has nothing to disclose. Conflict of interest: M.W. Pijnenburg has nothing to disclose. Conflict of interest: J. Grigg reports honoraria for advisory boards from GSK, Vifor Pharmaceuticals, BV Pharma and AstraZeneca, and an honorarium for a talk from Novartis, outside the submitted work., (Copyright ©ERS 2020.)

Pneumonia is an important cause of morbidity and mortality in children. We described viral aetiologies, with particular interest in detecting SARS-CoV-2, in hospitalized pneumonia children. Human rhinovirus was the most frequently detected agent. No children tested positive for SARS-CoV-2. Our findings suggest that SARS-CoV-2 infection is rare in children and it was not circulating in Rome before COVID-19 outbreak., Competing Interests: Declaration of Competing Interest Authors have nothing to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: A study of respiratory syncytial virus-A (RSV A) genotype ON1 genetic variability and clinical severity in infants hospitalized with bronchiolitis over 6 epidemic seasons (2012-2013 to 2017-2018) was carried out., Methods: From prospectively enrolled term infants hospitalized for bronchiolitis, samples positive for RSV A ON1 (N = 139) were sequenced in the second half of the G gene. Patients' clinical data were obtained from medical files and each infant was assigned a clinical severity score. ANOVA comparison and adjusted multinomial logistic regression were used to evaluate clinical severity score and clinical parameters., Results: The phylogenetic analysis of 54 strains showed 3 distinct clades; sequences in the last 2 seasons differed from previous seasons. The most divergent and numerous cluster of 2017-2018 strains was characterized by a novel pattern of amino acid changes, some in antigenic sites. Several amino acid changes altered predicted glycosylation sites, with acquisition of around 10 new O-glycosylation sites. Clinical severity of bronchiolitis increased in 2016-2017 and 2017-2018 and changed according to the epidemic seasons only., Conclusions: Amino acid changes in the hypervariable part of G protein may have altered functions and/or changed its immunogenicity, leading to an impact on disease severity., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The role of human bocavirus (HBoV) as a respiratory pathogen has not been fulfilled yet. We aimed to describe clinical and serological characteristics of children with HBoV hospitalized for acute respiratory tract infection and to evaluate whether differences occur between HBoV alone and in co-infection., Methods: We retrospectively reviewed data from 60 children (median age of 6.2 months, range 0.6-70.9) hospitalized for acute respiratory symptoms, with HBoV detected from a respiratory sample, using a reverse transcriptase-PCR for 14 respiratory viruses (including respiratory syncytial virus (RSV), influenza virus A and B, human coronavirus OC43, 229E, NL-63 and HUK1, adenovirus, rhinovirus, parainfluenza virus1-3, and human metapneumovirus)., Results: HBoV was detected alone in 29 (48.3%) patients, while in co-infection with other viruses in 31 patients (51.7%), with a peak between December and January. Among the 60 patients, 34 were bronchiolitis, 19 wheezing, 3 pneumonia, 2 upper respiratory tract infection, and 2 whooping cough. Seven children (11.6%) required admission to the paediatric intensive care unit (PICU) for respiratory failure. No differences was observed in age, family history for atopy and/or asthma, clinical presentations, chest X-ray, or laboratory findings in children with HBoV alone vs. multiple viral detection. RSV was the most frequently co-detected virus (61.3%). When compared with HBoV detection alone, the co-detection of RSV and HBoV was associated with male sex (P = 0.013), younger age (P = 0.01), and lower blood neutrophil count (P = 0.032)., Conclusions: HBoV can be detected alone and in co-infection respiratory samples of children with an acute respiratory tract infection. A cause-effect relationship between HBoV and respiratory infection is not clear, so further studies are needed to clarify this point.

Respiratory Syncytial Virus (RSV) is the leading cause of bronchiolitis, and the severity may be influenced by the bacterial ecosystem. Our aim was to analyze the nasal microbiota from 48 infants affected by bronchiolitis from RSV virus and 28 infants with bronchiolitis but negative for the virus. Results showed a significantly lower biodiversity in the RSV-positive group with respect to the RSV-negative group, a specific microbial profile associated with the RSV-positive group different from that observed in the negative group, and significant modifications in the relative abundance of taxa in the RSV-positive group, as well as in the RSV-A group, with respect to the negative group. Furthermore, microbial network analyses evidenced, in all studied groups, the presence of two predominant sub-networks characterized by peculiar inter- and intra-group correlation patterns as well as a general loss of connectivity among microbes in the RSV-positive group, particularly in the RSV-A group. Our results indicated that infants with more severe bronchiolitis disease, caused by RSV-A infection, present significant perturbations of both the nasal microbiota structure and the microbial relationships. Patients with a milder bronchiolitis course (RSV-B-infected and patients who have cleared the virus) presented less severe alterations.

Aim: The most frequent cause of lower respiratory tract infection in infants is bronchiolitis. Up to now there is no agreement on the upper limit age of bronchiolitis. Our aim was to identify if there are clinical differences in infants hospitalized for bronchiolitis between 0-6 months and 6-12 months of age. A secondary aim was to establish whether there was differences in terms of recurrent wheezing at 12, 24, and 36 months of follow-up. Methods: We retrospectively analyzed clinical and virological records of 824 infants hospitalized for bronchiolitis during 11 consecutive epidemic seasons. From each infant at admission to the hospital nasopharyngeal washing was collected, clinical severity was assessed and clinical data were extracted from a structured questionnaire. At 12-24-36 months after discharge, parents were interviewed seeking information on recurrent wheezing. Results: A total of 773 infants (Group1) were ≤6 months of age, while 51 were >6 months (Group 2). No differences between family history for atopy and passive smoking exposure were observed between the two groups. Respiratory syncyzial virus was detected more frequently in Group 1 and human bocavirus in Group 2. The clinical severity score ( p = 0.011) and the use of intravenous fluids ( p = 0.0001) were higher in Group 1 with respect to Group 2 infants. At 36 months follow-up 163/106 (39.4%) Group 1 and 9/9 Group 2 infants experienced recurrent wheezing ( p = 0.149). Conclusion: We demonstrated that 0-6 months old infants bronchiolitis differs from > 6 months bronchiolitis., (Copyright © 2020 Nenna, Frassanito, Petrarca, Di Mattia and Midulla.)

Aim: To test the hypothesis that the balance of type-1/type-2 immune response differs between infants hospitalized with respiratory syncytial virus (RSV) bronchiolitis during the peak months and those during the nonpeak months., Methods: We prospectively enrolled 90 unrelated full-term previously healthy infants hospitalized during the first year of life for RSV sole bronchiolitis over 2 epidemics (November 2016 to April 2017 and October 2017 to April 2018). We stratified infants as follows: hospitalized during the peak months (n: 71) and during the nonpeak months (n: 19). The frequencies of CD4+ producing interferon (IFN)-γ and interleukin (IL)-4 and of CD8+ producing IFN-γ T cells were measured by flow cytometry from infant peripheral whole blood. The T-helper cell (Th2) polarization index was calculated as the ratio between CD4+ T cells producing IL-4 and CD4+ T cells producing IFN-γ., Results: Infants hospitalized during nonpeak months were significantly less frequently breast-fed, had a higher eosinophils count, a significantly higher percentage of CD4+ T cells producing IL-4 and higher Th2 polarization index than infants hospitalized during the peak months., Conclusions: We elucidated the presence of different endotypes in infants with RSV sole bronchiolitis. Previously healthy full-term infants hospitalized during the nonpeak months seem to be more likely those with a possible predisposition to atopy.