A systematic literature review was conducted up to 15th February 2022 to summarize long COVID evidence and to assess prevalence and clinical presentation in children and adolescents. Articles ...reporting long COVID prevalence and symptoms based on original data in the paediatric population were included. Case series quality was assessed through the JBI Critical Appraisal Checklist. For observational studies, adherence to STROBE checklist was evaluated. Twenty-two articles were included: 19 observational studies (12 cohort/7 cross-sectional) and 3 case series. Nine studies provided a control group. We found a high variability in terms of prevalence (1.6–70%). The most frequently reported symptoms were fatigue (2–87%), headache (3.5–80%), arthro-myalgias (5.4–66%), chest tightness or pain (1.4–51%), and dyspnoea (2–57.1%). Five studies reported limitations in daily function due to long COVID. Alterations at brain imaging were described in one study, transient electrocardiographic abnormalities were described in a minority of children, while most authors did not evidence long-term pulmonary sequelae. Older age, female sex, and previous long-term pathological conditions were more frequently associated with persistent symptoms.
Conclusion
: Long COVID evidence in children is limited, heterogeneous, and based on low-quality studies. The lockdown consequences are difficult to distinguish from long COVID symptoms. High-quality studies are required: WHO definition of long COVID should be used, controlled clinical studies should be encouraged, and the impact of new variants on long COVID prevalence should be investigated to ensure an objective analysis of long COVID characteristics in children and a proper allocation of healthcare system resources.
What is Known:
• Children rarely develop a severe respiratory disease in the acute phase of COVID-19.
• A limited number of patients develop a multisystem inflammatory condition that can lead to multiorgan failure and shock.
What is New:
• Persistent symptoms after SARS-CoV-2 infection are reported in children and limitations in daily function due to long COVID symptoms affect school attendance.
• Functional complaints of post-acute COVID are difficult to be distinguished from those due to social restrictions.
Emotional disorders, namely anxiety and depression, frequently affect adolescents with asthma. In addition, their parents also may present emotional problems. The objective of this study was to ...investigate anxiety and depression in asthmatic adolescents and in their parents in a real-life setting. A series of adolescents with allergic asthma were consecutively enrolled. Asthma was diagnosed according to the GINA document and consistently the symptom control grade was assessed. We used the HADS questionnaire for the adolescents, and HADS, STAY, and BDI questionnaires for their parents. Globally, 121 adolescents (71 males, 50 females, mean age 13.4±0.8 years, age ranging between 12 and 15 years) with allergic asthma and their parents were evaluated. Only 29% of adolescents had controlled asthma. Adolescents with controlled asthma had lower HADS-A and HADS-D scores than other patients, whereas there was no difference among parents. Severe maternal anxiety was more frequent in poorly controlled subjects than in partially controlled ones; absence of maternal anxiety was more common in controlled subjects. The preliminary results of the current study suggest that anxiety and depression are common in adolescents suffering from asthma as well as in their parents, mainly in mothers. Emotional disorders might affect also the asthma control. Thus, in clinical practice, the psychological assessment could be included in the asthma work-up.
The evolution in immunological methods used to assess human allergic diseases has led to the identification of immunoglobulin E (IgE) as a diagnostic biomarker and a potential therapeutic target. ...Innovative technologies in molecular biology and immunogenetics contributed to the development of a selective blocking agent, disclosing new therapeutic perspectives in the treatment of allergic asthma. Omalizumab is the most advanced humanized anti-IgE monoclonal antibody that specifically binds serum-free IgE. Omalizumab also interrupts the allergic cascade by preventing binding of IgE with FcεRI receptors on mast cells, basophils, antigen-presenting cells and other inflammatory cells.
This review discusses the discovery strategy and preclinical development of omalizumab. Furthermore, it also provides a clinical overview of the key trials leading to its launch and a detailed analysis of safety and post-marketing data.
The clinical efficacy of omalizumab in allergic asthma has been well documented in clinical trials, involving adults, adolescents and children with moderate-to-severe and severe allergic asthma. To date, omalizumab has also been approved in chronic idiopathic urticaria for patients 12 years and older who remain symptomatic despite high dosages of H1 antihistamines. Omalizumab has also been investigated in many other different patient populations beyond allergic asthma and may yet have an application to other indications. While omalizumab is the only mAb available for treating allergic asthma, the authors anticipate that new mAbs will emerge in the future that overcome omalizumab's current limitations.
Severe asthma in children remains a significant issue. It places a heavy burden on affected individuals and society as a whole in terms of high morbidity, mortality, consumption of healthcare ...resources, and side effects from high-dose corticosteroid therapy. New, targeted biologic therapies for asthma have emerged as effective add-on options, complementing our expanding understanding of asthma phenotypes/endotypes and the underlying immunopathology of the disease spectrum. They include omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. Omalizumab represents the first available therapeutic option for allergic asthma in patients as young as 6 years of age. Its efficacy and safety have been established by several randomized controlled trials specifically conducted in pediatric patients, leading to its final registration > 10 years ago. Three new interleukin (IL)-5 targeted agents, mepolizumab, reslizumab, and benralizumab, have been approved for the treatment of severe eosinophilic asthma starting from 6 years of age, and varying by country. More recently, dupilumab, a targeted agent against the IL-4 receptor α-chain, was approved for patients ≥12 years of age in the United States after pivotal trials were completed. The late-stage clinical testing of these targeted agents has mostly involved patients aged 12 years and up, and the application of those data to younger children can be inappropriate and carry risk. The efficacy and safety of these newer biologics in children should be supported by adequate research within this targeted age group. In this review, we will present the most recent evidence on these five biological therapies for severe asthma and will discuss dosage and administration, their efficacy, safety, and future prospects, with a focus on the pediatric age group, defined as age < 18 years.
Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of ...clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host's innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.
Asthma exacerbations in children is one of the most common medical conditions requiring urgent visits to primary healthcare providers or emergency departments, and even hospitalisations. Currently, ...there is significant variation in the management of asthma exacerbations expressed in guideline recommendations
clinical practice. This disconnect affects diagnostic and treatment decisions for the clinician and patient.
We systematically reviewed the available guidelines providing recommendations for diagnostic and therapeutic management of asthma exacerbations in the paediatric population.
A systematic review of the literature for guidelines published between January 2009 and October 2019 was conducted, using a protocol registered with the international prospective register of systematic reviews (PROSPERO CRD42020221562).
16 asthma exacerbation clinical practice guidelines for children were included. Despite general agreement between guidelines on the definition of asthma exacerbation, there was great variability in the definition of disease severity and assessment of asthma control. This systematic review also highlighted a paucity of recommendations for criteria for hospitalisation and discharge. Many guidelines scored poorly when measured for stakeholder involvement and editorial independence.
Comprehensive and updated guidelines compliant with international standards for clinical guidelines may significantly improve clinical practice quality, promote evidence-based recommendations and provide uniformity of treatment between countries.
•Worldwide, the prevalence of asthma is high among teenagers and school children.•Monitoring adverse events following coronavirus disease 2019 (COVID-19) vaccination is important for ...practitioners.•There are plans for mass COVID-19 vaccination of teenagers and school children.•The effect of COVID-19 vaccination on asthmatic individuals is unknown and unreported.•This article reports the first case of asthma exacerbation following COVID-19 vaccination.
There is ongoing debate regarding the role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in asthma exacerbation, and its long-term impact on the lung function of individuals with asthma. In contrast, the potential impact of coronavirus disease 2019 (COVID-19) vaccination on asthma is entirely unexplored.
This study examined a challenging case of severe asthma exacerbation in a 28-year-old female following two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech) at IRCCS Policlinico San Matteo in Pavia, Italy. The patient, a fourth-year resident at the hospital, was vaccinated in early 2021. She was an occasional smoker with a 10-year history of asthma and seasonal allergic rhinitis. She tested negative for SARS-CoV-2 on several molecular swabs and serology tests.
After receiving the second dose of vaccine, the patient started to experience worsening of respiratory symptoms. Following several episodes and a severe asthma attack, the patient required treatment with mepolizumab, a biologic drug (interleukin-5) antagonist monoclonal antibody.
This single case study is insufficient to draw conclusions about the association between asthma exacerbation and the COVID-19 vaccine. While the cause–effect link between vaccination against SARS-CoV-2 and worsening of asthmatic disease might only be suggested at present, this case is a valuable prompt for further investigation. This is particularly true from the perspective of mass vaccination of adolescents and children currently underway across the globe.
Emotional problems, such as anxiety and depression, are a relevant co-morbidity in severe asthma. Anxiety and depression may also be common in the parents of asthmatic adolescents. The current study ...evaluated anxious and depressive symptoms in 40 adolescents suffering from severe asthma, and in their parents, before and after 1 year of treatment, tailored according to validated asthma guidelines. We used the HADS (Hospital Anxiety Depression Scale) questionnaire for the adolescents, and HADS, STAY (State-Trait Anxiety Inventory), and BDI (Beck Depression Inventory) questionnaires for their parents. We also considered the grade of asthma severity before and after 1 year of treatment. The current study demonstrated that anxiety and depression are common in both the adolescents suffering from severe asthma and their parents. Anxious and depressive symptoms were correlated between adolescents and their parents. Asthma treatment improved the asthma severity in almost all adolescents. However, the parental anxiety and depression remained unchanged at the end of the asthma treatment. Thus, a psychological assessment could be included in the adolescent severe asthma work-up, involving both the adolescents and their parents.
Tryptophan metabolic pathway is involved in pathogenic mechanisms of asthma. This study aimed to evaluate tryptophan metabolites and neopterin in a group of asthmatic children. Tryptophan metabolites ...and neopterin were measured in asthmatic children (121, 71 males, 50 females, mean age 11.6 + 3.2 years) and well-matched healthy controls (63, 32 males, 31 females, mean age 10.7 + 2.6 years). Tryptophan, kynurenine, and neopterin levels were significantly higher in asthmatic children than in healthy controls (p < 0.01; p < 0.01; p = 0.0015 respectively). Tryptophan metabolites and neopterin are increased in asthmatic children; these mediators underline the complex mechanisms involved in the immune response in asthma.
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