Currently, it remains unclear why some children develop invasive group A Streptococcus (iGAS) and how to manage this condition. Therefore, to explore available works in the literature, we performed a scoping review aiming to analyze the current literature on clinical presentation of different illnesses outcomes of iGAS, with a specific focus on predictors of invasive infection, including an assessment of the prodromal stages of the disease and the possible presence of previous non-invasive GAS infections in children that later developed iGAS. Methods: We conducted a systematic search on PubMed and SCOPUS of all pediatric studies reporting iGAS cases, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. For those studies in which multivariable analysis investigating iGAS risk factors was performed, a second review was performed and reported in detail. Results: A total of 209 studies were included. Five studies investigated risk factors for iGAS, the most relevant being varicella infection, chronic underlying illness, presence of the speC gene in GAS strains, acetaminophen and ibuprofen use, children nonwhite, living in low-income households, exposure to varicella at home, persistent high fever, having more than one other child in the home, and new use of NSAIDs. Although we observed a progressive increase in the number of papers published on this topic, no trials investigating the benefits of clindamycin or intravenous immunoglobulins were found and low-to-middle-income countries were found to be poorly represented in the current literature. Conclusions: Our scoping review highlights important gaps regarding several aspects of iGAS in children, including prodromic presentation and optimal treatment strategies. There is also little representation of low–middle-income countries. The current literature does not allow the performance of systematic reviews or meta-analyses, but this work should inform healthcare professionals, policy makers, and funding agencies on which studies to prioritize on this topic.

Olfactory dysfunction is one of the long-term consequences of acute SARS-CoV-2 infection in adults. This study aims to analyze the prevalence of chronic anosmia among COVID-19 children and to bring to light its impact on their families’ quality of life and wellbeing. Children younger than 18 years old, who were detected as being COVID-19-positive by RT-PCR and were assessed in a pediatric post-COVID outpatient clinic at least 28 days after the onset of the acute infection, were included in the study. The patients suffering from persisting smell disorders were asked to answer a questionnaire about their symptoms and how they influence their daily life. Out of the 784 children evaluated, 13 (1.7%) presented olfactory impairment at a mean follow-up since the acute infection of more than three months. Parents’ answers showed that they were worried about their children’s health, in particular they wanted to know if and when they would recover and if these disorders would have long-term consequences. They also wanted to share their experiences, in order to help other people who are experiencing the same disorders in everyday life. Our study highlights that smell disorders can significantly upset children’s eating habits and everyday activities. Furthermore, these findings suggest that future research should try to better understand the mechanisms causing loss of smell in COVID-19 patients and find the most appropriate treatment.

Introduction: Central nervous system (CNS) infections represent some of the most critical pediatric health challenges, characterized by high mortality rates and a notable risk of long-term complications. Despite their significance, standardized guidelines for endocrinological follow-up of CNS infection survivors are lacking, leading to reliance on the expertise of individual centers and clinicians. Materials and Methods: Prospective monocentric observational study conducted at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, Italy. It included patients with a history of CNS infection, admitted to various pediatric departments of the hospital. The participants were selected based on a coded diagnosis of CNS infection and had completed their follow-up at the Pediatric Endocrinology Day Hospital after October 2019. Results: Eighty participants were included, comprising 53 patients with a prior CNS infection and 27 healthy controls, with a median age of 7.4 years (range 3.6–12.3 years). Endocrinologic alterations were detected in 13 patients, with 8 cases in those who had meningitis, 4 in encephalitis survivors, and 1 in a patient with a cerebral abscess. Patients with a history of CNS infections were shorter compared with healthy controls (P = 0.027). Moreover, those who had meningitis exhibited an increased risk of developing epilepsy (P = 0.01), neurosensory disabilities (P = 0.034) and the need for ventriculoperitoneal shunt insertion (P = 0.006). Patients with bacterial CNS infections were more prone to neurosensory and endocrine dysfunctions compared to those with viral or other infections. Significant differences were observed in hormone levels between previously infected patients and controls, specifically in TSH (P < 0.001), ACTH (P = <0.001), and cortisol (P = 0.019). IGF-1 levels were considerably lower in the infection group, both in absolute terms and when adjusted for sex and age (P < 0.001). The regression analysis suggested that the reduction in IGF-1 was more pronounced the earlier the CNS infection occurred, irrespective of infection type. Conclusions: Our study found several endocrinologic imbalances in children who survived CNS infections.

Purpose The incidence of endocrine sequelae following central nervous system (CNS) infections in pediatric age is not known. We conducted this scoping review to assess the incidence of endocrinological alterations in patients with prior CNS infections in pediatric age. Methods Our screening process included both randomized and non-randomized controlled trials. All types of observational studies, prospective and retrospective, have been included. Results Ten studies were included in our review. The cumulative number of patients in all of the studies was 211, the mean age of the population study was 4.9 (±5 years). The included papers described the following acute CNS infections: meningitis (nine studies reported eighty-five cases) and encephalitis (three studies described sixty-five cases). Two case reports and one retrospective study reported hypopituitarism as a consequence of Mycobacterium tuberculosis CNS infection. In five studies the patients developed endocrine comorbidities at the time of infection. Another study analyzed 49 young adults who previously had tuberculous meningitis at a mean age of 5.9 ± 5.0 years: seven patients had growth hormone deficiency, four of whom also had gonadotropin deficiency; the other three had gonadotropin deficiency, corticotropin deficiency, and mild hyperprolactinemia. Conclusion Standardized multidisciplinary follow-up and research of patients with prior CNS infection is crucial. Although pituitary reserve screening is not commonly performed in these patients, clinical and research centers should set up an endocrinological evaluation with monitoring of auxological parameters to detect the signs and symptoms of hypopituitarism early and to initiate the appropriate care in children with previous CNS infections.

Commercially available Interferon-γ release assays (IGRAs), including the last-generation QuantiFERON TB-Plus (QFT-Plus), are effective in aiding the diagnosis of tuberculosis (TB) infection but cannot distinguish latent TB subjects from active TB patients. The aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA, combined with commercially available IGRAs, to assess their usefulness as a prognostic biomarkers and aid in the monitoring of TB treatment in children. Following clinical, microbiological, and radiological assessment, children younger than 18 years of age classified as either LTBI or active TB were tested at baseline and during treatment by the QuantiFERON TB-Plus (QFT) assay and an aliquot of whole-blood was stimulated with HBHA. Among the 655 children evaluated, 559 (85.3%) were classified as “Non TB”, 44 patients (6.7%) with active TB, and 52 (7.9%) with LTBI. The median HBHA-IGRA IFN-gamma responses were able to discriminate active TB from LTBI (0.13 IU/ml vs 1.995, (p < 0,0001), those with asymptomatic TB from those with symptomatic TB (1.01 IU/ml vs 0.115 IU/ml, p 0.017), or more severe TB (p 0.022), and significantly raised during successful TB treatment (p < 0.0001). Conversely, CD4 + and CD8 + responses were similar in all groups of patients, although active TB patients had higher CD4 + responses and LTBI higher CD8 + responses.  Conclusion: HBHA-based IGRA, combined with CD4 + and CD8 + responses assessed by commercially available IGRAs, is a useful support in the characterization of the TB spectrum in children and monitoring of TB-therapy. What is Known:• Current immune diagnostics are not able to discriminate active and latent Ttuberculosis, including the recently approved QFT-PLUS..• New immunological assays with prognostic value are highly needed. What is New:• HBHA-based IGRA, combined with CD4+ and CD8+ responses assessed by commercially available IGRAs, is a useful support for the differentiation of active and latent TB in children..• HBHA-based IGRA, combined with CD4+ and CD8+ responses assessed by commercially available IGRAs, is a useful support in the monitoring of TBtherapy in children..