Comparative study showed that children faced a 78% higher risk of new-onset conditions after they had COVID-19.

AIM: Children have largely been unaffected by severe COVID-19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID-19 and healthy controls. METHODS: A retrospective nested cohort study assessed the incidence rate of new-onset conditions after COVID-19 in children aged 0-14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. RESULTS: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1-3.0) and neurological problems (aHR 2.4, 95% CI 1.4-4.1). CONCLUSION: Exposed children had a 78% higher risk of developing new conditions of interest after COVID-19 than unexposed children.

How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review.

Background: Post Coronavirus disease (COVID) and other post-viral infection syndromes present an overlap of pathogenesis, onset, progression, and symptom profile. We aimed to systematically describe studies on post-viral conditions and determine the entity of post COVID compared to other post-viral conditions in children. Methods: We conducted a systematic search of the Embase, MEDLINE, Cochrane Library, and GoogleScholar databases (January 1946-3 November 2023), according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The main outcomes were differences in condition duration, symptom type, and development of chronic symptoms. This systematic review was registered on PROSPERO (CRD42023401789). Findings: 35/5051 studies were included, with 42,934 children, adolescents and young adults (0-20 years old) overall. Twenty-eight studies focused on post COVID symptoms, followed by five papers on Respiratory Syncytial Virus (RSV) and Rhinovirus, one study on Epstein-Barr Virus (EBV), and one on gastrointestinal viruses. Studies on post COVID mainly reported data on older children/adolescents, describing long-lasting symptoms, including fatigue, neurologic, cardiorespiratory, musculoskeletal, mental health, and gastrointestinal symptoms. The maximum described symptoms duration was eighteen months, with an average follow-up of seven months. The development of chronic symptoms was reported by 30 studies (93.8%) for 10,473/28,474 patients (36.8%). Recovery was achieved in 18,001/28,474 cases (63.2%). The study on EBV reported persistent fatigue in adolescents for a similar duration (6 months, 46% chronic). Studies on RSV and Rhinovirus were mainly done in children under three years, with development of recurrent wheezing (up to 3 years). Interpretation: Post-viral fatigue was a shared feature between post COVID and post EBV conditions. A better understanding of post COVID as a unique condition, sharing features with other post-viral syndromes, is needed. The healthcare burden and socio-economic consequences for children and their families warrant further investigation and development of appropriate healthcare management plans. The foremost requirement is the establishment of consistent and shareable definitions, as well as a consensus on outcomes, to effectively evaluate follow-up and quantify the burden of different viral infections. Funding: EU Horizon, EDCTP, NIH.

Biomarkers in IBD: What to Utilize for the Diagnosis?

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process; the performance is better in Crohn's disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap, but the long half-life, the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Impact of guidelines implementation on empiric antibiotic treatment for pediatric uncomplicated osteomyelitis and septic arthritis over a ten-year period: Results of the ELECTRIC study (ostEomyeLitis and sEptiC arThritis tReatment in children).

Background: Due to the growing evidence of the efficacy of intravenous (IV) cefazolin with an early switch to oral cefalexin in uncomplicated pediatric osteomyelitis (OM) and septic arthritis (SA) in children, we changed our guidelines for empiric antibiotic therapy in these conditions. This study aims at evaluating the impact of the guidelines' implementation in reducing broad-spectrum antibiotic prescriptions, duration of IV antibiotic treatment and hospital stay, treatment failure and recurrence. Materials and methods: This is a retrospective, observational, quasi-experimental study. The four years pre-intervention were compared to the six years, ten months post-intervention (January 2012, through December 2015; January 2016, through October 31st, 2022). All patients aged 3 months to 18 years with OM or SA were evaluated for inclusion. Each population was divided into three groups: pre-intervention, post-intervention not following the guidelines, and post-intervention following the guidelines. Differences in antibiotic prescriptions such as Days of Therapy (DOT), activity spectrum and Length of Therapy (LOT), length of hospital stay (LOS), broad-spectrum antibiotics duration (bsDOT), treatment failure and relapse at six months were analyzed as outcomes. Results: Of 87 included patients, 48 were diagnosed with OM (8 pre-intervention, 9 post-intervention not following the guidelines and 31 post-intervention following the guidelines) and 39 with SA (9 pre-intervention, 12 post-intervention not following the guidelines and 18 post-intervention following the guidelines). In OM patients, IV DOT, DOT/LOT ratio, and bsDOT were significantly lower in the guidelines group, with also the lowest proportion of patients discharged on IV treatment. Notably, significantly fewer cases required surgery in the post-intervention groups. Considering SA, LOS, IV DOT, DOT/LOT ratio, and bsDOT were significantly lower in the guidelines group. The treatment failure rate was comparable among all groups for both OM and SA. There were no relapse cases. The overall adherence was between 72 and 100%. Conclusions: The implementation of guidelines was effective in decreasing the extensive use of broad-spectrum antibiotics and combination therapy for both OM and SA. Our results show the applicability, safety, and efficacy of a narrow-spectrum IV empirical antibiotic regimen with cefazolin, followed by oral monotherapy with first/second-generation cephalosporins, which was non-inferior to broad-spectrum regimens.

Clinical features of COVID-19 in Italian outpatient children and adolescents during Parental, Delta, and Omicron waves: a prospective, observational, cohort study.

Introduction: COVID-19 features changed with the Omicron variant of SARS-CoV-2 in adults. This study aims to describe COVID-19 symptoms in children and adolescents during the Parental, Delta, and Omicron eras. Methods: A single-centre, prospective observational study was conducted on individuals aged 0-20 years attending the University Hospital of Padua (Italy) from April 2020 to December 2022. COVID-19 cases were defined by positive SARS-CoV-2 molecular detection and/or serology; patient/family symptoms and virological positivity were considered to determine the infection onset. Variables were summarized and compared using appropriate tests of descriptive statistics. Results: A total of 509 cases [46% female, median age eight years (IQR: 4-12)] were studied. Three-hundred-eighty-seven (76%), 52 (10%), and 70 (14%) subjects experienced COVID-19 during the Parental, Delta, and Omicron waves, respectively. All subjects developed an asymptomatic/mild COVID-19. Overall, the most frequent symptoms were fever (47%) and rhinitis (21%), which showed a significant increasing incidence from the Parental to Omicron waves (p < 0.001). Conversely, diarrhea was most common during the pre-Omicron eras (p = 0.03). Stratifying symptoms according to the age group, fever, rhinitis, and skin rashes were observed more frequently among infants/toddlers; conversely, fatigue was more common in children older than five years. The duration of symptoms was similar across different SARS-CoV-2 variants of concern (VOCs); conversely, the number of symptoms varied according to the age group (p < 0.0001). Discussion: This study showed differences in COVID-19 clinical presentation among infants, children, and adolescents and confirmed Omicron infection is more likely to be associated with upper respiratory symptoms. However, further population-based studies are needed to support these findings. In addition, active surveillance will play a crucial role in assessing the disease severity of future VOCs.

Long-term management of Fontan patients: The importance of a multidisciplinary approach.

The Fontan operation is a palliative procedure that leads to increased survival of patients with a functional single ventricle (SV). Starting from 1967 when the first operation was performed by Francis Fontan, more and more patients have reached adulthood. Furthermore, it is expected that in the next 20 years, the population with Fontan circulation will reach 150,000 subjects. The absence of right ventricular propulsion and the inability to improve cardiac output because of the low cardiac reserve are the main issues with the Fontan circulation; however, potential complications may also involve multiple organ systems, such as the liver, lungs, brain, bones, and the lymphatic system. As these patients were initially managed mainly by pediatric cardiologists, it was important to assure the appropriate transition to adult care with the involvement of a multidisciplinary team, including adult congenital cardiologists and multiple subspecialists, many of whom are neither yet familiar with the pathophysiology nor the end-organ consequences of the Fontan circulation. Therefore, the aim of our work was to collect all the best available evidence on Fontan's complications management to provide "simple and immediate" information sources for practitioners looking for state of the art evidence to guide their decision-making and work practices. Moreover, we suggest a model of follow-up of patients with Fontan based on a patient-centered multidisciplinary approach.