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Background Various bacterial and viral assemblages composing Cystic Fibrosis (CF) lung microbiota contribute to long-term lung function decline over time. Yet, the impact of individual microorganisms on pulmonary functions remains uncertain in children with CF. Methods As part of the 'Mucoviscidosis, respiratory VIruses, intracellular Bacteria and fastidious organisms'' project, children with CF were longitudinally followed in a Swiss multicentric study. Respiratory samples included mainly throat swabs and sputa samples for bacterial culture and 16S rRNA metagenomics and nasopharyngeal swabs for respiratory virus detection by molecular assays. Percentage of predicted Forced Expiratory Volume in one second (FEV1%) and Lung Clearance Index (LCI) were recorded. Results Sixty-one children, of whom 20 (32.8%) presented with at least one pulmonary exacerbation, were included. Almost half of the 363 nasopharyngeal swabs tested by RT-PCR were positive for a respiratory virus, mainly rhinovirus (26.5%). From linear mixed-effects regression models, P. aeruginosa (-11.35, 95%CI [-17.90; -4.80], p = 0.001) was significantly associated with a decreased FEV1%, whereas rhinovirus was associated with a significantly higher FEV1% (+4.24 95%CI [1.67; 6.81], p = 0.001). Compared to conventional culture, 16S rRNA metagenomics showed a sensitivity and specificity of 80.0% and 85.4%, respectively for detection of typical CF pathogens. However, metagenomics detected a bacteria almost twice more often than culture. Conclusions As expected, P. aeruginosa impacted negatively on FEV1% while rhinovirus was surprisingly associated with better FEV1%. Culture-free assays identifies significantly more pathogens than standard culture, with disputable clinical correlation.

Background Veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a standard procedure for patient with refractory shock in Pediatric Intensive Care Unit (PICU). There is a paucity of data on the time relationship between VA-ECMO support, nosocomial infection occurrence, and PICU length of stay (LOS). The aim of this study was to determine the characteristics and impact of ECMO-related infections. Methods This is a retrospective study from 01/2008 to 12/2014, enrolling children with a VA-ECMO support for > 6 h. We recorded the first PICU infection during the VA-ECMO run, defined as a positive microbiological sample with clinical signs of infection or clinical signs of severe infection without positive sample. Results During the study period, 41 patients (25/41 male) were included, with a median age of 41.2 months (IQR 12.9–89.9) and a 53% mortality rate. Median time on VA-ECMO was 4.2 d (IQR 2–7.1), median PICU LOS was 14.7 d (IQR 4,7–26,9). Overall, 34% patients developed an infection, with an incidence of 60/1000 VA-ECMO days. Median time to first infection was 4 d (IQR 3–5), with Pseudomonas spp. being the most commonly detected microorganism (42%). Infected sites were ventilator-associated pneumonia (9/14), sternotomy infection (2/14), bloodstream (2/14) and urinary tract infections (1/14). Longer VA-ECMO support (> 5 d) (OR 5.9 (CI 95% 1.4–24.6; p = 0.01) and longer PICU stay (> 14 d) (OR 12 (95% CI 2.2–65.5; p = 0.004) were associated with infection. Conclusion In this single-center study, we underlined the high proportion and early occurrence of infections in patient on VA-ECMO, mostly in the first week. As infection was an early event, it may prolong the duration of VA-ECMO support and PICU LOS. Further research is needed to better understand the impact of infections on VA-ECMO and develop prevention strategies.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

PURPOSE With the growing importance of professionalism in medical education, it is imperative to develop professionalism assessments that demonstrate robust validity evidence. The Professionalism Mini-Evaluation Exercise (P-MEX) is an assessment that has demonstrated validity evidence in the authentic clinical setting. Identifying the factorial structure of professionalism assessments determines professionalism constructs that can be used to provide diagnostic and actionable feedback. This study examines validity evidence for the P-MEX, a focused and standardized assessment of professionalism, in a simulated patient setting. METHOD The P-MEX was administered to 275 pediatric residency applicants as part of a 3-station standardized patient encounter, pooling data over an 8-year period (2012 to 2019 residency admission years). Reliability and construct validity for the P-MEX were evaluated using Cronbach's alpha, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA). RESULTS Cronbach's alpha for the P-MEX was 0.91. The EFA yielded 4 factors: doctor-patient relationship skills, interprofessional skills, professional demeanor, and reflective skills. The CFA demonstrated good model fit with a root-mean-square error of approximation of .058 and a comparative fit index of .92, confirming the reproducibility of the 4-factor structure of professionalism. CONCLUSIONS The P-MEX demonstrates construct validity as an assessment of professionalism, with 4 underlying subdomains in doctor-patient relationship skills, interprofessional skills, professional demeanor, and reflective skills. These results yield new confidence in providing diagnostic and actionable subscores within the P-MEX assessment. Educators may wish to integrate the P-MEX assessment into their professionalism curricula.

BACKGROUND SARS-CoV-2 infection triggers different auto-antibodies, including anti-apolipoprotein A-1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID-19, and the impact of AAA1 on the inflammatory response and symptoms persistence. METHODS All serologies were assessed at one, three, six, and twelve months in 193 hospital employees with COVID-19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient-reported COVID-19 symptoms persistence at 12 months. Interferon (IFN)-α and-γ production by AAA1-stimulated human monocyte-derived macrophages (HMDM) was assessed in vitro. RESULTS AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID-19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti-SARS-COV2 serologies decreased, but remained significant. From the 3rd month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72-0.74; p

More than two years into the COVID-19 pandemic, most of the population has developed anti-SARS-CoV-2 antibodies from infection and/or vaccination. However, public health decision-making is hindered by the lack of up-to-date and precise characterization of the immune landscape in the population. Here, we estimated anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland.We conducted a population-based serosurvey between April 29 and June 9, 2022, recruiting children and adults of all ages from age-stratified random samples of the general population of Geneva, Switzerland. We tested for anti-SARS-CoV-2 antibodies using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein, and for antibody neutralization capacity against different SARS-CoV-2 variants using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. We estimated seroprevalence and neutralization capacity using a Bayesian modeling framework accounting for the demographics, vaccination, and infection statuses of the Geneva population.Among the 2521 individuals included in the analysis, the estimated total antibodies seroprevalence was 93.8% (95% CrI 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies in a representative subsample (N = 1160) ranged from 79.5% (77.1-81.8) against the Alpha variant to 46.7% (43.0-50.4) against the Omicron BA.4/BA.5 subvariants. Despite having high seroprevalence of infection-induced antibodies (76.7% [69.7-83.0] for ages 0-5 years, 90.5% [86.5-94.1] for ages 6-11 years), children aged12 years had substantially lower neutralizing activity than older participants, particularly against Omicron subvariants. Overall, vaccination was associated with higher neutralizing activity against pre-Omicron variants. Vaccine booster alongside recent infection was associated with higher neutralizing activity against Omicron subvariants.While most of the Geneva population has developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, less than half has neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection confers the greatest neutralization capacity, including against Omicron.General Directorate of Health in Geneva canton, Private Foundation of the Geneva University Hospitals, European Commission ("CoVICIS" grant), and a private foundation advised by CARIGEST SA.

Objectives International data on listeriosis during infancy from large populations are essential to guide evidence-based empiric antibiotic guidelines for sepsis in infancy. We aimed to determine the incidence, clinical manifestations, and outcome of listeriosis in infants Methods Prospective, active surveillance of listeriosis in infants Results In Canada, eight sporadic listeriosis cases were reported (incidence, 1.1/100,000 live births/year). In Switzerland, four cases were reported (incidence, 4.5/100,000 live births/year) of which three were part of a confirmed outbreak with an unclear source. In the two countries, eight of the 12 cases (66.6%) presented as early-onset disease (within the first 7 days of life) and none presented after 28 days life. Conclusions Neonatal listeriosis is rare. Infants presenting with sepsis, especially after 4 weeks of life, may not routinely require empiric antibiotic coverage for listeriosis. Outbreak-related cases still occur. Continued surveillance is important.

Immune compromised children are threatened by a higher risk of infections; some of these are preventable by vaccination. Primary care physicians play a fundamental role in optimising vaccination status. In this narrative review, we present the evidence on vaccine safety and immunogenicity in immune compromised children and discuss in which conditions live-attenuated vaccines can possibly be used. Vaccination schedules differ in some of these conditions, including the use of vaccines with higher antigenic contents (e.g. high-dose hepatitis B vaccine), additional vaccine doses (e.g. 2-dose schedule meningococcal vaccine), more frequent booster doses (e.g. life-long pneumococcal vaccine booster), supplementary vaccines (e.g. meningococcal B vaccine) and use of vaccines beyond the age of usual recommendation (e.g. Haemophilus influenza type b vaccine after 5 years of age). Serological monitoring is a useful tool for customizing vaccination schedule in immune compromised children, confirming adequate vaccine response and documenting seroprotection (especially against measles and varicella). Finally, verification of vaccination status of all household members can prevent them being vector of transmission of an infection to the immune compromised children. Conclusion: Intensified information strategies are needed to improve trust, rectify perceived risks and improve vaccine acceptability; primary physicians can play a critical role in the latter. What is Known:• Physician’s awareness is key to success, since it repeatedly correlates with higher vaccination rates What is New:• The vaccination status of immunocompromised children is rarely up-to-date• Knowing the latest vaccine recommendations is challenging, as they differ for each medical condition and change periodically• This review summarises the vaccine recommendations for children with compromised immune systems and highlights how paediatricians play a key role in coordinating their application

Background: Patients with inflammatory bowel disease (IBD) have a higher risk of infection and are frequently not up to date with their immunizations. Objectives: This study aims to review vaccination status and evaluate whether age, disease type, or treatment regimen could predict the absence of seroprotection against selected vaccine-preventable infection in adults with IBD. Methods: Cross-sectional study using questionnaire, immunization records review, and assessment of tetanus-specific, varicella-specific, and measles-specific immunoglobulin G concentrations. ClinicalTrials.gov: NCT01908283. Results: Among the 306 adults assessed (median age 42.7 years old, 70% with Crohn’s disease, 78% receiving immunosuppressive treatment), only 33% had an immunization record available. Absence of seroprotection against tetanus (6%) was associated with increasing age and absence of booster dose; absence of seroprotection against varicella (1%) or measles (3%) was exclusively observed in younger patients with Crohn’s disease. There was no statistically significant difference in immunoglobulin concentrations among treatment groups. Although vaccinations are strongly recommended in IBD patients, the frequencies of participants with at least 1 dose of vaccine recorded were low for nearly all antigens: tetanus 94%, diphtheria 87%, pertussis 54%, poliovirus 22%, measles-mumps-rubella 47%, varicella-zoster 0%, Streptococcus pneumoniae 5%, Neisseria meningitidis 12%, hepatitis A 41%, hepatitis B 48%, human papillomavirus 5%, and tick-borne encephalitis 6%. Conclusions: Although many guidelines recommend the vaccination of IBD patients, disease prevention through immunization is still often overlooked, including in Switzerland, increasing their risk of vaccine-preventable diseases. Serological testing should be standardized to monitor patients’ protection during follow-up as immunity may wane faster in this population.

Most children with fever without source (FWS) require diagnostic laboratory tests to exclude a serious bacterial infection (SBI), often followed by admission and empirical antibiotics. As febrile children with a viral infection are less likely to have a SBI, identifying patients with systemic viral infection could contribute to exclude SBI. We evaluated whether the presence of virus in the blood could be used as a biomarker to rule out SBI. Children p = 0.0225), compared to 5.5 for CRP ≥ 40 mg/l (p = 0.0009) and 3.7 for PCT ≥ 0.5 ng/mL (0.0093). This remained significant after adjusting for CRP and PCT (OR 5.6 and 5.9, respectively; p = 0.03 for both). Area under the ROC curve for CRP and PCT were 0.754 and 0.779, respectively, but increased to 0.803 and 0.832, respectively, when combined with viremia.Conclusion: The presence of viremia had a better performance than commonly used biomarkers to rule-out SBI and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS. Larger studies should evaluate the role of point-of-care testing of viruses by (revere-transcription) PCR in the plasma in management algorithms of children with FWS. What is Known:• Most children with FWS have a viral infection, but up to 15% have a SBI; most require laboratory tests, and many admission and empirical antibiotics.• Children with a viral infection are less likely to have a SBI. What is New:• Children with a systemic viral infection are less likely to have an SBI.• Viremia is a better predictor of absence of SBI than commonly used biomarkers and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS.

BackgroundVarious studies showed the negative impact of COVID-19-related lockdowns and school closures on the well-being of children and adolescents. However, the prevalence and consequences of occasional short-term school disruptions due to COVID-19-related quarantine or isolation remain unknown. This study evaluated their impact on the well-being and stress level of children and adolescents.MethodsIn June/July 2021, we conducted a survey selecting a representative sample of children and adolescents of a Swiss canton population. Parents of school-aged children reported information about them missing school because of COVID-19, from August 2020 to June 2021, as well as about their health-related quality of life (HRQoL) measured with the KINDL® scale and their stress level.ResultsAmong the 538 participants, 216/538 (40.1%) pupils missed school at least once for COVID-19-related causes, with a total of 272 absences. We observed no relationship between the frequency of COVID-19-related absences and the HRQoL or stress level, even when stratifying by the type of absence or socio-demographic factors.DiscussionOverall, these findings are reassuring in that quarantines and related school disruptions, which we know are a common and effective way of controlling SARS-CoV-2 transmission, did not seem to meaningfully impact children and adolescent’s wellbeing and stress. Finding the right balance between SARS-CoV-2 control and young populations’ well-being is challenging, and the current results provide additional information for decision makers.

In 208 children seeking medical care, the seropositivity rate of anti–SARS-CoV-2 IgG antibodies was 8.7%, suggesting an infection rate similar to that observed in adults but >100-fold the incidence of RT-PCR–confirmed pediatric cases. Compared with the gold-standard combined ELISA + immunofluorescence, the MEDsan IgG rapid diagnostic test performed accurately.

The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis.What is Known:•Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age.•Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture.What is New:•Vesicoureteric reflux (VUR) remains a risk factor for UTI butper seis neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended.•A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.

Background and AimsCOVID-19 vaccination has been in the spotlight for almost a year now, both within the scientific community and in the general population. The issue of healthcare workers' (HCWs) hesitancy is particularly salient, given that they are at the forefront of the fight against COVID-19. Not only could unvaccinated HCW spread the disease, but HCWs are also critical messengers in building confidence towards COVID-19 vaccines. The goal of this study was to examine the perception of COVID-19 risk and of its vaccine acceptance among employees (i.e., HCW plus administrative staff) in the Department of Paediatrics, Gynaecology and Obstetrics at the University Hospitals of Geneva, for the purpose of drawing lessons on the determinants of vaccination morale.MethodsWe conducted an anonymous online survey comparing vaccination attitudes among vaccinated and unvaccinated workers in June 2021. It included questions on perception of COVID-19 risks and COVID-19 vaccines. Vaccination was not mandatory in our institution but was strongly recommended.ResultsIn June 2021, 66% of the 1,800 employees of our department had received two doses of COVID-19 vaccine by the time of the survey. Among the employees, 776 participated (43%) to the survey, and among them 684 (88%) had chosen to be vaccinated. Participants working for longer in a hospital, with a chronic disease and a household contact with chronic disease were more likely to be vaccinated. Doctors were twice as likely to be vaccinated than nurses. Among unvaccinated hospital employees, 48 (52%) responded that they would not change their mind. Further, 35 (38%) were not feeling in danger of contracting severe COVID-19, and 32 (35%) had fears about possible side effects of COVID-19 vaccines that they wanted to discuss with a specialist.ConclusionOur study indicates that, while two-third of the employees had been vaccinated, quite many were still hesitant. The unvaccinated explained their choice by not feeling at risk of complicated COVID-19, and because of fear of possible side effects associated with the vaccine. Investments in COVID-19 vaccine education is a critical component for increasing vaccine acceptance among the unvaccinated.

COVID-19 vaccination has been successful in decreasing rates of SARS-CoV-2 infection in areas with high vaccine uptake. Cases of breakthrough SARS-CoV-2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID-19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID-19 vaccine formulations. Importantly, Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine studies have now included children as young as 5 years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5- to 11-year-old age group.Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID-19 vaccine data with focus on pediatric solid organ transplant (SOT)-specific issues.This review provides an overview of current COVID-19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge.Further studies of COVID-19 vaccination in pediatric SOT recipients are needed to better understand post-vaccine COVID-19 T-cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID-19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID-19 poses to pediatric solid organ transplant recipients.

BackgroundIt is now established that a significant proportion of adults experience persistent symptoms after SARS-CoV-2 infection. However, evidence for children and adolescents is still inconclusive. In this population-based study, we examine the proportion of children and adolescents reporting persistent symptoms after SARS-CoV-2 infection, as assessed by serological status, and compare this to a seronegative control group.MethodsWe conducted a serosurvey in June-July 2021, recruiting 660 children and adolescents from 391 households selected randomly from the Geneva population. We tested participants for anti-SARS-CoV-2 antibodies targeting the nucleocapsid (N) protein to determine previous infection. A parent filled a questionnaire including questions on COVID-19-related symptoms lasting at least 2 weeks.FindingsAmong children seropositive for anti-SARS-CoV-2 antibodies, the sex- and age-adjusted prevalence of symptoms lasting longer than two weeks was 18.3%, compared to 11.1% among seronegative children (prevalence difference (ΔaPrev)=7.2%, 95%CI:1.5-13.0). Main symptoms declared among seropositive children were fatigue (11.5%) and headache (11.1%). For 8.6% (aPrev, 95%CI: 4.7-12.5) of seropositives, these symptoms were declared to be highly limiting of daily activities. Adolescents aged 12-17 years had a higher adjusted prevalence of persistent symptoms (aPrev=29.1%, 95%CI:19.4-38.7) than younger children. Comparing seropositive and seronegative adolescents, the estimated prevalence of symptoms lasting over four weeks is 4.4% (ΔaPrev, 95%CI:-3.8-13.6).InterpretationA significant proportion of children aged 12 to 17 years had symptoms lasting over two weeks after SARS-CoV-2 infection, with an estimated prevalence of symptoms lasting over 4 weeks of 4.4% in this age group. This represents a large number of adolescents in absolute terms, and should raise concern in the context of unknown long-term evolution of symptoms. Younger children appear to experience long-lasting symptoms less frequently, as no difference was observed between the seropositive and seronegative sample. Further studies with larger samples sizes are needed.FundingSwiss Federal Office of Public Health, Geneva General Directorate of Health, HUG Private Foundation, SSPH+, Fondation des Grangettes.

We report a prospective epidemiological, virological and serological investigation of a SARS-CoV-2 outbreak in a primary school, as part of a longitudinal, prospective, primary school-based surveillance study. It involved repeated testing of pupils and teachers and household members of participants who tested positive, with rapid antigen tests and/or RT-PCR (Day 0-2 and Day 5-7), serologies on dried capillary blood samples (Day 0-2 and Day 30), contact tracing interviews and SARS-CoV-2 whole genome sequencing. This SARS-CoV-2 outbreak caused by the Alpha variant involved 20 children aged 4 to 6 years from 4 classes, 2 teachers and a total of 4 household members. Infection attack rates were between 11.8 and 62.0% among pupils from the 4 classes, 22.2% among teachers and 0% among non-teaching staff. Secondary attack rate among household members was 15.4%. Symptoms were reported by 63% of infected children, 100% of teachers and 50% of household members. All analysed sequences but one showed 100% identity. Serological tests detected 8 seroconversions unidentified by SARS-CoV-2 virological tests. This study confirmed child-to-child and child-to-adult transmission of the infection. Effective measures to limit transmission in schools have the potential to reduce the overall community circulation.

PurposeOur objective was to assess adolescent’s Health-Related Quality of Life (HRQoL) and psychological distress, from their own and their parents’ perspective, and to examine associated risk factors during the COVID-19 pandemic in Geneva, Switzerland.MethodsA random sample of adolescents, aged 14-17 years, and their families was invited to a serosurvey in November and December 2020. Adolescents’ HRQoL was evaluated using the validated adolescent-reported KIDSCREEN-10 and parent-reported KINDL® scales. Psychological distress was assessed with self-reported sadness and loneliness, and using the KINDL® emotional well-being scale. Risk factors for adolescents’ low HRQoL and psychological distress were identified using generalized estimating equations and both adolescents’ and their parents’ perceptions were compared.ResultsAmong 240 adolescents, 11% had a low HRQoL, 35% reported sadness and 23% reported loneliness. Based on parents’ perception, 12% of the adolescents had a low HRQoL and 16% a low emotional well-being. Being a girl (aOR=3.29; 95%CI: 1.64-6.57), increased time on social media (aOR=2.05; 95%CI: 1.08-3.88), parents’ average to poor mood (aOR=2.81; 95%CI: 1.21-6.56) and average to poor household financial situation (aOR=2.30; 95%CI: 1.00-5.29) were associated with an increased risk of sadness. Mismatches between adolescents’ and their parents’ perception of HRQoL were more likely for girls (aOR=2.88; 95%CI: 1.54-5.41) and in households with lower family well-being (aOR=0.91; 95%CI: 0.86-0.96).ConclusionA meaningful proportion of adolescents experienced low well-being during the second wave of COVID-19. Adolescents living in underprivileged or distressed families seemed particularly affected. Monitoring is necessary to evaluate the long-term effects of the pandemic on adolescents.Implications and ContributionThis study describes the psychological well-being of a population-based sample of adolescents in Geneva, Switzerland amid the COVID-19 pandemic, and identifies adolescents at risk of distress. This study provides further insight by comparing adolescents’ well-being as reported by themselves and their parents.

BackgroundUp-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape in the population and guide public health measures. We aimed to estimate the seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and six months into the vaccination campaign.MethodsWe conducted a population-based cross-sectional serosurvey between June 1 and July 7, 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins (Roche Elecsys immunoassays). We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies).ResultsWe included 3355 individuals, of which 1814 (54.1%) were women, 697 (20.8%) were aged ConclusionsMost adults have developed anti-SARS-CoV-2 antibodies, while most teenagers and children remain vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and socioeconomically disadvantaged groups, and to minimize spread among children.

BackgroundImprovement of paediatric healthcare is hampered by inefficient processes of generating new evidence. Clinical research often requires extra encounters with patients, is costly, takes place in an artificial situation with a biased selection of patients, and entails long delays until new evidence is implemented into health care. Electronic health records (EHR) contain detailed information on real patients and cover the entirety of patients. However, the use of EHR for research is limited because they are not standardized between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality.AimsSwissPedData aims to lay the foundation for a paediatric learning health system in Switzerland by facilitating EHR-based research. In this project, we aimed to assess the way routine clinical data are currently recorded in large paediatric clinics in Switzerland and to develop a national EHR-based common data model (CDM) that covers all processes of routine paediatric care in hospitals.MethodsA taskforce of paediatricians from large Swiss children’s hospitals reviewed the current status of routine data documentation in paediatric clinical care and the extent of digitalization. We then used a modified Delphi method to reach a broad consensus on a national EHR-based CDM.ResultsAll Swiss children’s hospitals use EHR to document some or all aspects of care. 119 paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national CDM that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 common data elements (CDEs): 76 in the main module on general paediatrics and between 11 and 59 CDEs per subspecialty module. Among these, 266 were classified as mandatory, 52 as recommended and 18 as optional.ConclusionSwissPedData is a CDM for information to be collected in EHR of Swiss children’s hospitals. It covers all care processes including clinical and paraclinical assessment, diagnosis, treatment, disposition and care site. All participating hospitals agreed to implement SwissPedData in their clinical routine and clinic information systems. This will pave the way for a national paediatric learning health system in Switzerland that enables fast and efficient answers to urgent clinical questions by facilitating high-quality nationwide retrospective and prospective observational studies and recruitment of patients for nested prospective studies and clinical trials.

La mononucleose infectieuse aigue est un probleme frequent en medecine de ville. Dans 90% des cas, la mononucleose est due au virus Epstein-Barr (EBV) – pour de nombreux medecins, «EBV» et «mononucleose» sont synonymes. Le diagnostic n’est pas toujours facile, et certaines personnes atteintes ne presentent pas d’autres symptomes que la fatigue.

Die akute infektiose Mononukleose, oft auch Pfeiffersches Drusenfieber genannt, ist ein haufiges Problem in der Praxis. In 90% wird die Mononukleose durch das Epstein-Barr-Virus (EBV) verursacht – fur viele Arztinnen und Arzte sind «EBV» und «Pfeiffer» synonym. Die Diagnose ist nicht immer ganz einfach, zum Teil haben die Betroffenen ausser Mudigkeit wenig andere Symptome, und die Serologie ist nicht immer eindeutig.

Background Population‐level COVID‐19 immunization will play a key role in slowing down the SARS‐CoV‐2 pandemic on a global scale and protect the most at‐risk individuals. Thanks to a formidable universal effort, several SARS‐CoV‐2 vaccines have been marketed less than a year since the first documented COVID‐19 case, with promising safety, efficacy, and immunogenicity results in adults. As children were not included in the initial trials, no vaccine is currently approved for individuals

To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19).We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay.Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2; p 0.001), and 6 (123.3 U/mL, 95%CI: 103.4-147.0; p 0.001) in the whole cohort. Anti-N antibodies were detectable in97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6; p 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4; p 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r 0.86, p 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics.Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.

The COVID‐19 pandemic has proven to be a challenge in regard to the clinical presentation, prevention, diagnosis, and management of SARS‐CoV‐2 infection among children who are candidates for and recipients of SOT. By providing scenarios and frequently asked questions encountered in routine clinical practice, this document provides expert opinion and summarizes the available data regarding the prevention, diagnosis, and management of SARS‐CoV‐2 infection among pediatric SOT candidates and recipients and highlights ongoing knowledge gaps requiring further study. Currently available data are still lacking in the pediatric SOT population, but data have emerged in both the adult SOT and general pediatric population regarding the approach to COVID‐19. The document provides expert opinion regarding prevention, diagnosis, and management of SARS‐CoV‐2 infection among pediatric SOT candidates and recipients.

Cholecalciferol (vitamin D3) is essentially known for its role in the phosphocalcic metabolism and its associated pathologies, such as rickets. In Switzerland, 35 to 50% of children are vitamin D deficient. Due to skin colour, poor nutrition, living conditions and cultural practices, migrant population is particularly at risk. Our aim is to attest the prevalence of hypovitaminosis D in children arriving in Switzerland. We retrospectively assessed 528 children’s vitamin D status and parathyroid hormone, phosphate and calcium levels between 2015 and 2018 by electrochemiluminescence and spectrophotometry. Cholecalciferol was considered insufficient under 50 nmol/L and severely deficient below 25 nmol/L. Seventy-three percent of children showed hypovitaminosis D and 28% had a severe deficiency. Highest prevalence of deficiency was found in children from Eastern Mediterranean (80%) and African regions (75%). Severe deficiency was more prevalent in the South East Asian (39%) and Eastern Mediterranean regions (33%) and more frequent in females. Deficiency was more frequent and more severe in winter. Hypovitaminosis D increased with age. Two children presented with all three biological manifestations associated to severe hypovitaminosis D (hyperparathyroidism, hypocalcaemia and hypophosphatemia).Conclusion: A majority of migrant children presented with hypovitaminosis D. They should be supplemented to prevent complications. A strategy could be to supplement all children at arrival and during wintertime without regular vitamin D level checks. What is Known:Hypovitaminosis D is frequent in children and can lead to bone-related complications.Migrant children are particularly at risk of deficiency. What is New:Three-quarters of migrant children evaluated at our migrant clinic in Geneva’s children hospital are deficient in vitamin D, one third severely.A strategy to correct the deficiency would be to supplement all migrant children at arrival and in winter.

The article “Swiss consensus recommendations on urinary tract infections in children”

Background Up-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape and to guide public health decisions. Aim We estimate seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and 6 months into the vaccination campaign. Methods We conducted a population-based cross-sectional serosurvey between 1 June and 7 July 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins using the Roche Elecsys immunoassays. We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies). Results Among 3,355 individuals (54.1% women; 20.8% aged Conclusion Most of the population has developed anti-SARS-CoV-2 antibodies, despite most teenagers and children remaining vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and to minimise spread among children.

Background. The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of underlying PID. We applied whole-exome sequencing (WES) to a national cohort of children with sepsis to identify rare, predicted pathogenic variants in PID genes., Methods. We conducted a multicenter, population-based, prospective study including previously healthy children aged >= 28 days and, Results. There were 176 children presenting with 185 sepsis episodes who underwent WES (median age, 52 months; interquartile range, 15.4-126.4). There were 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants that were previously reported to lead to PID. The variants occurred in PID genes across all 8 PID categories, as defined by the International Union of Immunological Societies. We did not observe a significant correlation between clinical or laboratory characteristics of patients and the presence or absence of PID variants., Conclusions. Applying WES to a population-based cohort of previously healthy children with bacterial sepsis detected variants of uncertain significance in PID genes in 1 out of 5 children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility.

Objectives: The contribution of intracellular and fastidious bacteria in Cystic fibrosis (CF) pulmonary exacerbations, and progressive lung function decline remains unknown. This project aimed to explore their impact on bacterial microbiota diversity over time in CF children. Methods: Sixty-one children enrolled in the MUCOVIB multicentre prospective cohort provided 746 samples, mostly nasopharyngeal swabs, throat swabs and sputa which were analysed using culture, specific real-time qPCRs and 16S rRNA amplicon metagenomics. Results: Chlamydia pneumoniae (n = 3) and Mycoplasma pneumoniae (n = 1) were prospectively documented in 6.6% of CF children. Microbiota alpha-diversity in children with a documented C. pneumoniae was highly variable, similarly to children infected with Staphylococcus aureus or Pseudomonas aeruginosa. The transition from routine follow-up visits to pulmonary exacerbation (n = 17) yielded variable changes in diversity indexes with some extreme loss of diversity. Conclusions: The high rate of C. pneumoniae detection supports the need for regular screenings in CF patients. A minor impact of C. pneumoniae on the microbial community structure was documented. Although detected in a single patient, M. pneumoniae should also be considered as a possible aetiology of lung infection in CF subjects., This study documented Chlamydia pneumoniae in 4.9% of children with cystic fibrosis, stressing the need for routine screening, and investigated its impact on airway microbiota by 16S amplicon-based metagenomics.

BACKGROUND: Varicella and measles infections can be life-threatening after solid organ transplantation (SOT) but may be preventable with live-attenuated vaccines (LAV). METHODS: This survey conducted in January 2019 among subscribers of the International Pediatric Transplantation Association listserv aimed to explore the current strategies to prevent and manage both infections in the pediatric SOT population, including recommending LAV after SOT. RESULTS: The answers given by 95 pediatric SOT healthcare workers show that these strategies are not yet optimal and call for further education. In particular, 59% of respondents are unnecessarily waiting for a SOT candidate to be >1 year of age to start administrating LAV before SOT. Interestingly, most respondents are willing to administer LAV after SOT (57%), and a fifth (21%) are already doing so, off-label. The survey queried the precautions taken to improve safety evaluations after LAV, and identified knowledge gaps and practitioners' concerns. CONCLUSION: The results of this survey could be used as a starting point for education and promotion of the safe administration of LAV in carefully selected SOT recipients; in turn, this would increase available data that would contribute to the development of evidence-based guidelines by the transplant societies and ultimately prevent these infections after SOT.

* Abbreviations: COVID-19 — : coronavirus disease HHC — : household contact IQR — : interquartile range SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Since the onset of coronavirus disease (COVID-19) pandemic, children have been less affected than adults in terms of severity1–3 and frequency, accounting for

BackgroundAssessing the burden of COVID-19 based on medically-attended case counts is suboptimal given its reliance on testing strategy, changing case definitions and the wide spectrum of disease presentation. Population-based serosurveys provide one avenue for estimating infection rates and monitoring the progression of the epidemic, overcoming many of these limitations.MethodsTaking advantage of a pool of adult participants from population-representative surveys conducted in Geneva, Switzerland, we implemented a study consisting of 8 weekly serosurveys among these participants and their household members older than 5 years. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available enzyme-linked immunosorbent assay (Euroimmun AG, Lübeck, Germany). We estimated seroprevalence using a Bayesian regression model taking into account test performance and adjusting for the age and sex of Geneva’s population.ResultsIn the first three weeks, we enrolled 1335 participants coming from 633 households, with 16% InterpretationAssuming that the presence of IgG antibodies is at least in the short-term associated with immunity, these results highlight that the epidemic is far from burning out simply due to herd immunity. Further, no differences in seroprevalence between children and middle age adults are observed. These results must be considered as Switzerland and the world look towards easing restrictions aimed at curbing transmission.

Background: Hepatitis A is endemic in many countries. Swiss guidelines recommend vaccinating patients native from endemic areas. In Geneva's Children's hospital, migrant children are screened and vaccinated if seronegative. Because hepatitis A's prevalence is decreasing worldwide, more children are seronegative at arrival, highlighting the need for immunization in medical centers and refugee camps and questioning the benefits of systematic serology. Other Swiss hospitals vaccinate regardless of serostatus. This study's aim is to assess migrant children's immunity according to origin and age, and the cost-effectiveness of different immunization strategies. Methods: We retrospectively analyzed 329 children's serostatus (1-16 years of age) between 2012 and 2015, using enzyme-linked fluorescent assay method. Serology and vaccine costs were based on local prices. Groups were compared with χ test and the age-seropositivity relationship was studied with linear regression. Results: The predominant regions were the Eastern Mediterranean and European Regions with mostly negative serologies (71% and 83%) and the African Region with mostly positive serologies (79%). Immunity varied depending on birth country. Regardless of region, seropositivity increased with age (P < 0.001). The most cost-effective vaccination strategy was an individualized approach based on age and origin, reducing costs by 2% compared with serology-guided immunization and by 17% compared with systematic vaccination. Conclusions: Many migrant children >5 years old are seronegative and at risk of clinical infection. They need to be immunized. New guidelines according to age and origin should be defined to reduce immunization costs. We recommend systematic vaccination for patients

Summary Background Assessing the burden of COVID-19 on the basis of medically attended case numbers is suboptimal given its reliance on testing strategy, changing case definitions, and disease presentation. Population-based serosurveys measuring anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies provide one method for estimating infection rates and monitoring the progression of the epidemic. Here, we estimate weekly seroprevalence of anti-SARS-CoV-2 antibodies in the population of Geneva, Switzerland, during the epidemic. Methods The SEROCoV-POP study is a population-based study of former participants of the Bus Santé study and their household members. We planned a series of 12 consecutive weekly serosurveys among randomly selected participants from a previous population-representative survey, and their household members aged 5 years and older. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. We estimated seroprevalence using a Bayesian logistic regression model taking into account test performance and adjusting for the age and sex of Geneva's population. Here we present results from the first 5 weeks of the study. Findings Between April 6 and May 9, 2020, we enrolled 2766 participants from 1339 households, with a demographic distribution similar to that of the canton of Geneva. In the first week, we estimated a seroprevalence of 4·8% (95% CI 2·4–8·0, n=341). The estimate increased to 8·5% (5·9–11·4, n=469) in the second week, to 10·9% (7·9–14·4, n=577) in the third week, 6·6% (4·3–9·4, n=604) in the fourth week, and 10·8% (8·2–13·9, n=775) in the fifth week. Individuals aged 5–9 years (relative risk [RR] 0·32 [95% CI 0·11–0·63]) and those older than 65 years (RR 0·50 [0·28–0·78]) had a significantly lower risk of being seropositive than those aged 20–49 years. After accounting for the time to seroconversion, we estimated that for every reported confirmed case, there were 11·6 infections in the community. Interpretation These results suggest that most of the population of Geneva remained uninfected during this wave of the pandemic, despite the high prevalence of COVID-19 in the region (5000 reported clinical cases over