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The emergence of novel SARS-CoV-2 variants of concern (VOCs) has altered the epidemiology and clinical characteristics of COVID-19. This study aims to describe the changes in COVID-19 manifestations in outpatients children and adolescents during the Parental, Delta, and Omicron eras.

Objectives SARS-CoV-2 serology presents an important role in several aspects of COVID-19 pandemic. Immunoassays performances have to be accurately evaluated and correlated with neutralizing antibodies. We investigated the analytical and clinical performances of a SARS-CoV-2 RBD IgG assay, automated on a high throughput platform, and the correlation of the antibodies (Ab) levels with the plaque reduction neutralization (PRNT50) Ab titers. Methods A series of 546 samples were evaluated by SARS-CoV-2 RBD IgG assay (Snibe diagnostics), including 171 negative and 168 positive SARS-CoV-2 subjects and a further group of 207 subjects of the COVID-19 family clusters follow-up cohort. Results Assay imprecision ranged from 3.98 to 12.18% being satisfactory at low and medium levels; linearity was excellent in all the measurement range. Considering specimens collected after 14 days post symptoms onset, overall sensitivity and specificity were 99.0 and 92.5%, respectively. A total of 281 leftover samples results of the PRNT50 test were available. An elevated correlation was obtained between the SARS-CoV-2 RBD IgG assay and the PRNT50 titer at univariate (ρ=0.689) and multivariate (ρ=0.712) analyses. Conclusions SARS-CoV-2 S-RBD IgG assay shows satisfactory analytical and clinical performances, and a strong correlation with sera neutralizing activity.

INTRODUCTION AND OBJECTIVE: Community-acquired pneumonia (CAP) is one of the most common reasons of prescribing antibiotics for children, often with overuse of broad-spectrum antibiotics. The aim of this study is to describe the antibiotic prescriptions for Italian children with CAP, at the primary care level. STUDY DESIGN: Retrospective cohort study conducted among children 3 months-14 years of age with CAP, enrolled in Pedianet (http://www.pedianet.it) from January 1, 2009 to December 31, 2018. Antibiotic treatment was defined as narrow-spectrum (NS-ABT) if amoxicillin and broad-spectrum (BS-ABT) if amoxicillin/clavulanic acid, cephalosporins or any combination. Crude and adjusted logistic regressions for the odds of receiving NS-ABT were conducted (all episodes of CAP and per patient). A P value

Importance: Understanding the long-term immune response against SARS-CoV-2 infection in children is crucial to optimize vaccination strategies. Although it is known that SARS-CoV-2 antibodies may persist in adults 12 months after infection, data are limited in the pediatric population. Objective: To examine long-term anti-SARS-CoV-2 spike receptor-binding domain (S-RBD) IgG kinetics in children after SARS-CoV-2 infection. Design, Setting, and Participants: In this single-center, prospective cohort study, patients were enrolled consecutively from April 1, 2020, to August 31, 2021, at the COVID-19 Family Cluster Follow-up Clinic, Department of Women's and Children's Health, University Hospital of Padua. A cohort of 252 COVID-19 family clusters underwent serologic follow-up at 1 to 4, 5 to 10, and more than 10 months after infection with quantification of anti-S-RBD IgG by chemiluminescent immunoassay. Exposures: SARS-CoV-2 infection. Results: Among 902 study participants, 697 had confirmed SARS-CoV-2 infection, including 351 children or older siblings (mean [SD] age, 8.6 [5.1] years) and 346 parents (mean [SD] age, 42.5 [7.1] years). Among 697 cases, 674 (96.7%) were asymptomatic or mild. Children had significantly higher S-RBD IgG titers than older patients across all follow-up time points, with an overall median S-RBD IgG titer in patients younger than 3 years 5-fold higher than adults (304.8 [IQR, 139.0-516.6] kBAU/L vs 55.6 [24.2-136.0] kBAU/L, P

Comprehensive data are needed to monitor antibiotic prescribing and inform stewardship. We aimed to evaluate the current antibiotic prescribing patterns, including treatment switching and prolongation, in the paediatric primary care setting in Italy. This database study assessed antibiotic prescriptions retrieved from Pedianet, a paediatric primary care database, from 1 January 2012 to 31 December 2018. Descriptive analyses were stratified by diagnosis class, calendar year, and children’s age. Generalized linear Poisson regression was used to assess variation in the prescriptions. In total, 505,927 antibiotic prescriptions were included. From 2012 to 2018, the number of antibiotics per child decreased significantly by 4% yearly from 0.79 in 2012 to 0.62 in 2018. Amoxicillin prescriptions decreased with increasing children’s age, while macrolides and third-generation cephalosporins had the opposite trend. Prescriptions were associated with a diagnosis of upper respiratory infection in 23% of cases, followed by pharyngitis (21%), bronchitis and bronchiolitis (12%), and acute otitis media (12%). Eight percent of treatment episodes were prolonged or switched class, mostly represented by co-amoxiclav, macrolides, and third-generation cephalosporins. Our findings report an overall decrease in antibiotic prescriptions, but pre-schoolers are still receiving more than one antibiotic yearly, and broad-spectrum antibiotics prescription rates remain the highest.

BACKGROUND Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4–13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged CONCLUSIONS Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.

Aims Compared with adult patients, clinical manifestations of children’s coronavirus disease-2019 (COVID-19) are generally perceived as less severe. The objective of this study was to evaluate cardiac involvement in previously healthy children with asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Methods and results We analysed a cohort of 53 paediatric patients (29 males, 55%), mean age 7.5 ± 4.7 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or only mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study at least 3 months after diagnosis. Thirty-two age, sex, and body surface area comparable healthy subjects were used as control group. Left ventricular ejection fraction was within normal limits but significantly lower in the cases group compared to controls (62.4 ± 4.1% vs. 65.2 ± 5.5%; P = 0.012). Tricuspid annular plane systolic excursion (20.1 ± 3 mm vs. 19.8 ± 3.4 mm; P = 0.822) and left ventricular (LV) global longitudinal strain (−21.9 ± 2.4% vs. −22.6 ± 2.5%; P = 0.208) were comparable between the two groups. Regional LV strain analysis showed a significant reduction of the LV mid-wall segments strain among cases compared to controls. Furthermore, in the cases group, there were 14 subjects (26%) with a regional peak systolic strain below −16% (−2.5 Z score in our healthy cohort) in at least two segments. These subjects did not show any difference regarding symptoms or serological findings. Conclusion SARS-CoV-2 infection may affect left ventricular deformation in 26% of children despite an asymptomatic or only mildly symptomatic acute illness. A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes.

In the Veneto Region, an exponential spread of patients affected by 2019 novel Coronavirus disease (COVID-19) has been observed after February 21st. Since then, we have been evaluating children suspected or confirmed for SARS-CoV-2 infection. A protocol for pediatric hospital reorganization and children management has been developed, since the beginning of the epidemic. A pre-triage area has been created at the immediate entrance of the pediatric emergency room, for all uncritical pediatric patients. According to the epidemiologic and clinical risk factors, all children/adolescents have been addressing to one of the four different pathways created. The strict application of this protocol has been leading to quickly identification, isolation, and management of all positive children, preventing SARS-CoV-2 intrahospital spread.

Background and setting Little is known about SARS-CoV-2 impact on some vulnerable subgroups, such as people living with HIV/AIDS (PLWHA). In our study we reviewed the current knowledge on SARS-CoV-2 cases in PLWHA. Methods A systematic review was conducted by searching the MEDLINE, EMBASE and Google Scholar databases. Studies reporting data on PLWHA affected by SARS-CoV-2 were considered for inclusion. The aim of this study was the systematic characterization of cases of SARS-CoV-2 infection among PLWHA, particularly focusing on age, clinical findings at diagnosis, radiological features, therapeutic management and clinical outcomes. Results Twenty three relevant articles were identified, which reported 164 adults with both HIV and SARS-CoV-2 infection. Of those, the large majority were males (120/142, 84.5%), often with one or more comorbidities. Fifteen cases needed intensive care treatment and 16 died. For each group, respectively three patients had underlying comorbidities. There were no studies on children. The included studies were mostly retrospective or case series/reports (19 studies). The overall risk of bias was moderate, due to the study types and characteristics. Conclusion It is still unclear if HIV infection may influence SARS-CoV-2 infection and disease course, however some PLWHA and particularly males affected by ARV-related complications may be at greater risk of severe Covid-19 course.

Optimizing the use of antibiotics has become mandatory, particularly for the pediatric population where limited options are currently available. Selecting the dosing strategy may improve overall outcomes and limit the further development of antimicrobial resistance. Time-dependent antibiotics optimize their free concentration above the minimal inhibitory concentration (MIC) when administered by continuous infusion, however evidences from literature are still insufficient to recommend its widespread adoption. The aim of this review is to assess the state-of-the-art of intermittent versus prolonged intravenous administration of antibiotics in children and neonates with bacterial infections. We identified and reviewed relevant literature by searching PubMed, from 1 January 1 2000 to 15 April 2020. We included studies comparing intermittent versus prolonged/continuous antibiotic infusion, among the pediatric population. Nine relevant articles were selected, including RCTs, prospective and retrospective studies focusing on different infusion strategies of vancomycin, piperacillin/tazobactam, ceftazidime, cefepime and meropenem in the pediatric population. Prolonged and continuous infusions of antibiotics showed a greater probability of target attainment as compared to intermittent infusion regimens, with generally good clinical outcomes and safety profiles, however its impact in terms on efficacy, feasibility and toxicity is still open, with few studies led on children and adult data not being fully extendable.

Since February 2020, Italy has been faced with the dramatic spread of novel Coronavirus SARS-CoV-2. This impetuous pandemic infection forced many hospitals to reorganize their healthcare systems. Predicting a rapid spread of the SARS-CoV-2 virus within our region, the Department for Women’s and Children’s Health promptly decided (i) to revise the distribution of the clinical areas in order to create both designated COVID-19 and COVID-19-free areas with their own access, (ii) to reinforce infection prevention control (IPC) measures for all healthcare workers and administrative staff and (iii) to adopt the new “double-gate approach”: a phone call pre-triage and nasopharyngeal swab for SARS-CoV-2 detection before the admission of all patients and caregivers. Between 21 February 2020 till 04 May 2020, only seven physicians, two nurses and two of the administrative staff resulted positive, all during the first week of March. No other cases of intra-department infection were documented among the healthcare workers since all the preventive procedures described above were implemented. It is predicted that similar situations can happen again in the future, and thus, it is necessary to be more prepared to deal with them than we were at the beginning of this COVID-19 pandemic.

Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.

Background. Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)–infected children of low-middleincome countries (LMIC). Methods. An observational study included HIV-infected children attending the Beira Central Hospital (Mozambique) and the Nsambya Hospital, Home Care Department (Uganda) evaluated clinical and immunological failure according to World Health Organization (WHO) 2006 guidelines. Baseline predictors for cART failure and for drug substitution were explored in unadjusted and adjusted Cox proportional hazard models. Results. Two hundred eighteen of 740 children with at least 24 weeks follow-up experienced treatment failure (29%; 95% confidence interval [CI] 26–33), with crude incidence of 20.0 events per 100 person-years (95% CI 17.5–22.9). Having tuberculosis co-infection or WHO stage 4, or starting a nontriple cART significantly increased risk of failure. Two hundred two of 769 (26.3%) children receiving cART substituted drug(s), with crude incidence of 15.4 events per 100 person-years (95% CI 13.4–17.7). Drug toxicity (18.3%), drug availability (17.3%), and tuberculosis drugs interaction (52, 25.7%) were main reported reasons, while only 9 (4%) patients switched cART for clinical or immunological failure. Children starting lamivudine-zidovudine-nevirapine or lamivudine-stavudineefavirenz or lamivudine-zidovudine-efavirenz were more likely to have substitute drugs. Increased substitution was found in children with mild immunosuppression and tuberculosis co-infection at cART initiation as well as poor adherence before drug substitution. Conclusions. Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.

Community Home-Based Care (CHBC) has evolved in resource-limited settings to fill the unmet needs of people living with HIV/AIDS (PLHA). We compare HIV and tuberculosis (TB) outcomes from the Nsambya CHBC with national averages in Kampala, Uganda. This retrospective observational study compared HIV and TB outcomes from adults and children in the Nsambya CHBC to national averages from 2007 to 2011. Outcomes included numbers of HIV and TB patients enrolled into care, retention, loss to follow-up (LTFU), and mortality among patients on antiretroviral therapy (ART) at 12 months from initiation; new smear-positive TB cure and defaulter rates; and proportion of TB patients tested for HIV. Chi-square test and trends analyses were used to compare outcomes from Nsambya CHBC with national averages. By 2011, approximately 14,000 PLHA had been enrolled in the Nsambya CHBC, and about 4,000 new cases of TB were detected and managed over the study period. Overall, retention and LTFU of ART patients 12 months after initiation, proportion of TB patients tested for HIV, and cure rates for new smear-positive TB scored higher in the Nsambya CHBC compared to national averages. The findings show that Nsambya CHBC complements national HIV and TB management and results in more positive outcomes.

Background Intensified tuberculosis (TB) case finding and isoniazid preventive therapy (IPT) are strongly recommended for children who are HIV infected. Data are needed to assess the feasibility of the WHO 2011 intensified tuberculosis case finding/IPT clinical algorithm. Methods Children who are HIV infected and attending Nsambya Home Care at Nsambya Hospital, Uganda, were screened for TB following WHO recommendations. IPT was given for 6 months after excluding TB. Factors associated with time to IPT initiation were investigated by multivariate Cox proportional hazard regression. Health care workers were interviewed on reasons for delay in IPT initiation. Results Among the 899 (49% male) children with HIV, 529 (58.8%) were screened for TB from January 2011 to February 2013. Children with active TB were 36/529 (6.8%), 24 (4.5%) were lost to follow-ups and 280 (52.9%) started IPT, 86/280 (30.7%) within 3 months of TB screening and 194/280 (69.3%) thereafter. Among the 529 children screened for TB, longer time to IPT initiation was independently associated with cough at TB screening (hazard ratio 0.62, P = 0.02, 95% confidence interval: 0.41 to 0.94). Four children (1% of those starting treatments) interrupted IPT because of a 5-fold increase in liver function measurements. In the survey, Health care workers reported poor adherence to antiretroviral therapy, poor attendance to periodic HIV follow-ups, and pill burden as the 3 main reasons to delay IPT. Conclusion In resource-constrained settings, considerable delays in IPT initiation may occur, particularly in children with HIV who are presenting with cough at TB screening. The good safety profile of isoniazid in antiretroviral-therapy-experienced children provides further support to IPT implementation in this population.

Correlations between clinical/immunological treatment failure and viral load (VL) detected by dried blood spot (DBS) sampling were explored in HIV-1-infected children in Uganda. Of 104 children on combined antiretroviral treatment (cART), 12.5% experienced clinical and/or immunological failure, while 28.8%, 44.2%, and 26.9% had VLs of 5,000 copies/ml, respectively. Clinical/immunological failure poorly predicted virological failure.

We describe factors determining retention and survival among HIV-infected children and adolescents engaged in two health care delivery models in Kampala, Uganda: one is a community home-based care (CHBC) and the other is a facility-based family-centred approach (FBFCA). This retrospective cohort study reviewed records from children aged from 0 to 18 years engaged in the two models from 2003 to 2010 focussing on retention/loss to follow-up, mortality, use of antiretroviral therapy (ART), and clinical characteristics. Kaplan Meier survival curves with log rank tests were used to describe and compare retention and survival. Overall, 1,623 children were included, 90.0% (1460/1623) from the CHBC. Children completed an average of 4.2 years of follow-up (maximum 7.7 years). Median age was 53 (IQR: 11–109) months at enrolment. In the CHBC, retention differed significantly between patients on ART and those not (log-rank test, adjusted, P<0.001). Comparing ART patients in both models, there was no significant difference in long-term survival (log-rank test, P=0.308, adjusted, P=0.489), while retention was higher in the CHBC: 94.8% versus 84.7% in the FBFCA (log-rank test, P<0.001, adjusted P=0.006). Irrespective of model of care, children receiving ART had better retention in care and survival.

We describe a fatal case of imported malaria where the sole finding revealed at thepostmortemevaluation was an acute lymphocytic myocarditis with myocardiolysis. This case recalls the potential importance of myocardial injury in the prognosis of malaria and prompts a reevaluation of current perspectives on the pathogenesis of severe falciparum infection. In the light of this, we have reviewed the cases of cardiac complications in malaria published to date.