COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children.

In children, the factors that influence COVID-19 disease and its medium- and long-term effects are little known. Our investigation sought to evaluate the presence of comorbidity factors associated with respiratory long COVID manifestations in children and to study ultrasound abnormalities following SARS-CoV-2 infection. Children, who arrived at the 'Respiratory Diseases of Pediatric Interest Unit' at the Department of Woman, Child, and General and Specialized Surgery of the University of Campania 'Luigi Vanvitelli', were selected during the timeframe from September 2021 to October 2022. The children were diagnosed with a SARS-CoV-2 infection that occurred at least one month before the visit. All patients followed a COVID-19 follow-up protocol, developed by the Italian Society of Pediatric Respiratory Diseases (SIMRI), which included: collection of data regarding SARS-CoV-2 illness and history of known respiratory and allergic diseases; physical examination; BMI assessment; baseline spirometry and after bronchodilation test; six-minute walking test; and lung ultrasound (LUS). In a cohort of 104 participants with respiratory long COVID symptoms (64.7% male, average age 8.92 years), 46.1% had fever with other symptoms, and 1% required hospitalization. BMI analysis showed 58.4% of the cohort was overweight. The LUS was positive in 27.0% of cases. A significant BMI association was observed with COVID-19 symptoms and LUS score (p-value < 0.05). No associations were found with asthma or atopy.

Latex Allergy in Children.

Notwithstanding the efforts made in the last decades to mitigate the consequences of natural rubber latex allergy, this disease continues to be a major health problem, especially in developing countries. The categories of patients with greater and frequent exposure to latex (such as health care professionals and, in the pediatric field, subjects who undergo repeated surgery, e.g., those suffering from spina bifida and urogenital malformations) have an increased risk of developing sensitization and allergy to latex. Herein we provide an overview of the current knowledge and practical recommendations with a focus on epidemiology, diagnostics, and management (including both prevention and therapy) in order to guide a correct recognition and containment of this potentially fatal condition.

Vitamin D status can affect COVID-19 outcomes also in pediatric population.

Background: vitamin D influences the immune system and the inflammatory response. It is known that vitamin D supplementation reduces the risk of acute respiratory tract infection. In the last two years, many researchers have investigated vitamin D's role in the pathophysiology of COVID-19 disease. Results: the findings obtained from clinical trials and systematic reviews highlight that most patients with COVID-19 have decreased vitamin D levels and low levels of vitamin D increase the risk of severe disease. This evidence seems to be also confirmed in the pediatric population. Conclusions: further studies (systematic review and meta-analysis) conducted on children are needed to confirm that vitamin D affects COVID-19 outcomes and to determine the effectiveness of supplementation and the appropriate dose, duration and mode of administration.

Tailored therapies for primary immunodeficiencies.

Primary immunodeficiency disorders (PIDs) are rare inherited monogenic disorders of the immune system, characterized by an increased risk of infection, immune dysregulation and malignancies. To date, more than 420 PIDs have been identified. The recent introduction of high throughput sequencing technologies has led to identifying the molecular basis of the underlying aberrant immune pathway, and candidate targets to develop precision treatment, aimed at modifying the clinical course of the disease. In PID, targeted therapies are especially effective to manage immune dysregulation and autoimmunity, also reducing the incidence of side effects compared to conventional treatments, sparing the use of steroids and immunosuppressive drugs. Moreover, in the last years, the approach of conventional treatments such as immunoglobulin replacement therapies has evolved and the indication has expanded to new diseases, leading to individualized strategies to both improve infection control and quality of life.  Similarly, the new advent of gene therapy in selected PIDs has introduced the benefit to correct the immunological defect, reducing at the same time the complications related to the hematopoietic stem cell transplantation. Here, we illustrate the most recent findings on tailored treatments for PIDs.

Tuberculosis and TNF-α inhibitors in children: how to manage a fine balance.

Since the introduction of biologic response modifiers (BRMs) in the management of children affected by the immune-mediated inflammatory disease, these patients substantially improved their quality of life. BRMs are generally well tolerated and effective in most children and adolescents refractory to conventional immunosuppressive therapy. On the other hand, patients receiving BRMs, especially TNF-α inhibitors, display an increased risk of primary infections or reactivations, i.e. due to Mycobacterium tuberculosis. M. tuberculosis can cause severe disease with consequent short- and long-term morbidity in children on anti-TNF-α treatment. The present paper analyses the increased risk of reactivation of latent tuberculosis infection (LTBI) or de novo TB infection in children treated with TNF-α inhibitors, with the purpose to provide recommendations for screening strategies and safety monitoring of paediatric patients. Special attention is also given to the currently available TB screening tools (IGRAs and TST) and their utility in the diagnosis of LTBI before starting the biologic therapy and during the treatment. Finally, the paper analyses the suggested TB-preventing therapies to adopt in these children and the correct timing to overlap anti-TB and anti-TNF-a treatment.

Update in Primary Immunodeficiencies.

Primary immunodeficiencies (PIDs) are inherited disorders classically characterized by increased susceptibility to infections. Nevertheless, in the last two decades, genomic analysis (such as NGS) coupled with biochemical and cellular studies led to a more accurate definition for a growing number of novel genetic disorders associated with PIDs. This revealed new aspects of the immune system and its function and regulation within these diseases. In particular, it has been clarified that the clinical features of PIDs are much broader that originally thought and extend beyond an increased susceptibility to infections. More specifi- cally, immune dysregulation is very often described in novel characterized PIDs and can lead to multiple autoimmune diseases, lymphoproliferation and malignancies. If not promptly diagnosed, these could negatively impact patient's prognosis. The aim of this review is to increase the awareness of recently discovered PIDs, characterized predominantly by immune dysregulation phenotypes. Findings highlighted in this review  suggest screening for immunodeficiency in patients with lymphoproliferation or early onset/multiple autoimmune diseases. Prompt diagnosis would potentially allow most successful treatment and clinical outcome for patients with PIDs.

Resveratrol plus carboxymethyl-ß-glucan reduces nasal symptoms in children with pollen-induced allergic rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction consequent to the exposure to causal allergen. Resveratrol is a natural non-flavonoid polyphenol, exerting anti-inflammatory activity; ß-glucan is a polysaccharide with immuno-modulatory properties. Thus, this study aimed to investigate whether these combined compounds are able of relieving nasal symptoms in children with AR due to pollen allergy. RESEARCH DESIGN AND METHODS: The present study was conducted as placebo-controlled, double-blinded, and randomized. Globally, 68 children (36 males; mean age 7.9 years) were treated with resveratrol plus ß-glucan or placebo (the diluent of active drug) two sprays (100 µL/spray) in each nostril three times/day for 2 months. Nasal symptoms, including itching, sneezing, rhinorrhea, and obstruction, were assessed at baseline and after treatment. Use of rescue medication, such as cetirizine syrup, was also evaluated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02130440. RESULTS: Children treated with active drug achieved a significant reduction in all nasal symptoms: itching (p = 0.0001), sneezing (p = 0.0009), rhinorrhea (p = 0.009), and obstruction (0.002) as well as antihistamine use (p = 0.003). Placebo did not affect nasal complaints and cetirizine use. The intergroup analysis showed that active treatment was significantly superior to placebo about reduction of AR symptoms and rescue medication use. CONCLUSIONS: The present preliminary study firstly showed that intranasal resveratrol plus carboxymethyl-ß-glucan is capable of significantly improving nasal symptoms in children with pollen-induced AR.