Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. METHODS: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness. RESULTS: Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock. CONCLUSION: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

Antibiotic therapy for osteoarticular infections in 2023: Proposals from the Pediatric Infectious Pathology Group (GPIP).

Most osteoarticular infections (OAI) occur via the hematogenous route, affect children under 5 years of age old, and include osteomyelitis, septic arthritis, osteoarthritis and spondylodiscitis. Early diagnosis and prompt treatment are needed to avoid complications. Children with suspected OAI should be hospitalized at the start of therapy. Surgical drainage is indicated in patients with septic arthritis or periosteal abscess. Staphylococcus aureus is implicated in OAI in children at all ages; Kingella kingae is a very common causative pathogen in children from 6 months to 4 years old. The French Pediatric Infectious Disease Group recommends empirical antibiotic therapy with appropriate coverage against methicillin-sensitive S. aureus (MSSA) with high doses (150 mg/kg/d) of intravenous cefazolin. In most children presenting uncomplicated OAI with favorable outcome (disappearance of fever and pain), short intravenous antibiotic therapy during 3 days can be followed by oral therapy. In the absence of bacteriological identification, oral relay is carried out with the amoxicillin/clavulanate combination (80 mg/kg/d of amoxicillin) or cefalexin (150 mg/kg/d). If the bacterial species is identified, antibiotic therapy will be adapted to antibiotic susceptibility. The minimum total duration of antibiotic therapy should be 14 days for septic arthritis, 3 weeks for osteomyelitis and 4-6 weeks for OAI of the pelvis, spondylodiscitis and more severe OAI, and those evolving slowly under treatment or with an underlying medical condition (neonate, infant under 3 months of old, immunocompromised patients). Treatment of spondylodiscitis and severe OAI requires systematic orthopedic advice.

Antimicrobial treatment of urinary tract infections in children.

Urinary tract infections are the most frequently proven bacterial infections in pediatrics. The treatment options proposed in this guide are based on recommendations published by the Groupe de Pathologie Infectieuse de Pédiatrique (GPIP-SFP). Except in rare situations (newborns, neutropenia, sepsis), a positive urine dipstick for leukocytes and/or nitrites should precede a urine culture examination and any antibiotic therapy. After rising steadily between 2000 and 2012, the proportion of Escherichia coli strains resistant to extended-spectrum ß-lactamases (E-ESBL) has remained stable over the last ten years (between 7% and 10% in pediatrics). However, in many cases no oral antibiotic is active on E-ESBL leading either to prolonged parenteral treatment, or to use of a non-orthodox combination such as cefixime + clavulanate. With the aim of avoiding penem antibiotics and encouraging outpatient management, this guide favors initial treatment of febrile urinary tract infections (suspected or actual E-ESBL infection), with amikacin. Amikacin remains active against the majority of E-ESBL strains. It could be prescribed as monotherapy for patients in pediatric emergency departments or otherwise hospitalized patients.

Quality indicators for appropriate antibiotic prescribing in urinary tract infections in children.

BACKGROUND: The aim of this study was to define a set of urinary tract infections (UTIs)-specific quality indicators for appropriate prescribing in children and evaluate clinical practices in a district general hospital in Greece. METHODS: The UTIs-specific quality indicators were informed by a review of the existing literature. Quality indicators were selected to describe the overall antibiotics use, prescribing patterns and UTIs clinical management regarding treatment and prophylaxis in a cohort of children admitted with a UTI. Microbiological, clinical and prescribing data about dosing, duration and route of administration were collected from the patients' electronic health records. RESULTS: Twelve quality indicators were adapted or developed for prescribing in childhood UTIs. A broad variety of antibiotics were prescribed for UTIs, with a drug utilization (DU) 90% rate of 6 and 9 different antibiotics for febrile and afebrile UTIs, respectively. Despite the low incidence of multi-drug resistant UTIs in the study period (9/261, 3.4%), broad-spectrum antibiotics were prescribed in 33.5% (164/490) of prescriptions. A total of 62.8% (164/261) of patients were started on empiric combined therapies, while opportunities to de-escalate were missed in 37.8% (62/164) of them. One quarter (67/261, 25.7%) of patients did not fulfil the criteria for receiving treatment, while nearly half of those prescribed prophylaxis (82/175, 46.9%) could have avoided having a prophylaxis prescription. CONCLUSIONS: Our study identified substantial gaps for improvement in antimicrobial prescribing for UTIs in children. The application of the proposed quality indicators could help to limit unnecessary antibiotics use in children with UTI.

A French study of cocaine intoxication/exposure in children (2010-2020).

BACKGROUND AND OBJECTIVE: In the European Union, the record of cocaine-related seizures indicates an expanding supply. The purity has also been increasing. The health impact of these trends remains poorly documented, in particular, the changes and clinical manifestations of intoxication in young children. We attempted to evaluate the trend in French pediatric admissions for cocaine intoxication/exposure over an 11-year period (2010-2020). METHODS: A retrospective, national, multicenter, study of a pediatric cohort. All children less than 15 years of age admitted to a tertiary-level pediatric emergency unit for proven cocaine intoxication (compatible symptoms and positive toxicological screening) during the reference period were included. RESULTS: Seventy-four children were included. Forty-six percent were less than 6 years old. Annual admissions increased by a factor of 8 over 11 years (+700%) and 57% of all cases were admitted in the last two years. The main clinical signs were neurologic (59%) followed by cardiovascular symptoms (34%). Twelve patients were transferred to the pediatric intensive care unit. Factors significantly associated with the risk of being transferred to the pediatric intensive care unit were initial admission to the pediatric resuscitation area (P < 0.001), respiratory impairment (P < 0.01), mydriasis (P < 0.01), cardiovascular symptoms (P = 0.014), age of less than 2 years (P = 0.014). Blood and/or urine toxicological screening isolated eighteen other substances besides cocaine in 46 children (66%). CONCLUSION: Children are collateral victims of the changing trends in cocaine availability, use and purity. Admissions of intoxicated children to pediatric emergency departments are more frequent and there is an increase in severe presentations. Therefore, this is a growing public health concern.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

Impact of lockdown on children with type-1 diabetes: returning to the community was associated with a decrease in HbA1c.

Background: In March 2020, a 2-month lockdown of the entire population has been declared in France to limit the spread of COVID-19. Sudden changes in daily life can impact the glycemic control of patients with type 1 diabetes (T1D), especially children and adolescents. We aimed to assess the impact of the lockdown on glycemic control in children and adolescents with T1D. Methods: Children with T1D were prospectively recruited in two pediatric centers from May 11 to August 1, 2020. At inclusion, patients and/or parents were asked to fill in a form assessing the patient's lifestyle during the lockdown and a medical case report form was filled in by clinician. The mean of the three last glycated hemoglobin (HbA1c) values obtained before lockdown (HbA1c_mean; before March 17, 2020) was compared to the first HbA1c value measured after the lockdown (HbA1c_after; from May 11 to August 1, 2020). Univariable and multivariable analyses were performed, as appropriate, to identify factors associated with glycemic changes during lockdown. Results: One-hundred-and-eighteen children and adolescents (median age was 14.1 years, 50% males) with T1D (median time from diagnosis was 4.1 years) were enrolled in the study. No significant difference was observed between medians of HbA1c_mean and HbA1c_after values (8.37% [7.88; 9.32%] vs. 8.50% [7.70; 9.50%], respectively; p = 0.391). Returning to the community was a protective factor [OR 0.31 (0.09-0.94); p = 0.045]. Patients having increased HbA1c were more frequently in contact with a suspected case of COVID-19 [OR 9.07 (2.15-53.66); p = 0.006], whereas patients having decreased HbA1c had the feeling of increase number of hypoglycemia [OR 0.19 (0.05-0.57); p = 0.006]. Conclusion: In our patients, HbA1c before and after the lockdown was stable. In subgroup analysis, returning to the community was a protective factor. In addition, feeling of hypoglycemia was more frequent in the patients with decreased HbA1c.

Performance Evaluation of Host Biomarker Combinations for the Diagnosis of Serious Bacterial Infection in Young Febrile Children: A Double-Blind, Multicentre, Observational Study.

The diagnosis of serious bacterial infection (SBI) in young febrile children remains challenging. This prospective, multicentre, observational study aimed to identify new protein marker combinations that can differentiate a bacterial infection from a viral infection in 983 children, aged 7 days-36 months, presenting with a suspected SBI at three French paediatric emergency departments. The blood levels of seven protein markers (CRP, PCT, IL-6, NGAL, MxA, TRAIL, IP-10) were measured at enrolment. The patients received the standard of care, blinded to the biomarker results. An independent adjudication committee assigned a bacterial vs. viral infection diagnosis based on clinical data, blinded to the biomarker results. Computational modelling was applied to the blood levels of the biomarkers using independent training and validation cohorts. Model performances (area under the curve (AUC), positive and negative likelihood ratios (LR+ and LR-)) were calculated and compared to those of the routine biomarkers CRP and PCT. The targeted performance for added value over CRP or PCT was LR+ ≥ 5.67 and LR- ≤ 0.5. Out of 652 analysed patients, several marker combinations outperformed CRP and PCT, although none achieved the targeted performance criteria in the 7 days-36 months population. The models seemed to perform better in younger (7-91 day-old) patients, with the CRP/MxA/TRAIL combination performing best (AUC 0.895, LR+ 10.46, LR- 0.16). Although computational modelling using combinations of bacterial- and viral-induced host-protein markers is promising, further optimisation is necessary to improve SBI diagnosis in young febrile children.

Saliva for molecular detection of SARS-CoV-2 in pre-school and school-age children.

SARS-CoV-2 diagnosis is a cornerstone for the management of coronavirus disease 2019 (COVID-19). Numerous studies have assessed saliva performance over nasopharyngeal sampling (NPS), but data in young children are still rare. We explored saliva performance for SARS-CoV-2 detection by RT-PCR according to the time interval from initial symptoms or patient serological status. We collected 509 NPS and saliva paired samples at initial diagnosis from 166 children under 12 years of age (including 57 children under 6), 106 between 12 and 17, and 237 adults. In children under 12, overall detection rate for SARS-CoV-2 was comparable in saliva and NPS, with an overall agreement of 89.8%. Saliva sensitivity was significantly lower than that of NPS (77.1% compared to 95.8%) in pre-school and school-age children but regained 96% when considering seronegative children only. This pattern was also observed to a lesser degree in adolescents but not in adults. Sensitivity of saliva was independent of symptoms, in contrary to NPS, whose sensitivity decreased significantly in asymptomatic subjects. Performance of saliva is excellent in children under 12 at early stages of infection. This reinforces saliva as a collection method for early and unbiased SARS-CoV-2 detection and a less invasive alternative for young children.

Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study.

BACKGROUND: During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. METHODS AND FINDINGS: Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. CONCLUSIONS: Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. TRIAL REGISTRATION: ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258.

Reassessing the Performance of the "Step-By-Step" Approach to Febrile Infants 90 Days of Age and Younger in the Context of the COVID-19 Pandemic: A Multicentric Retrospective Study.

BACKGROUND: Infants with COVID-19 can often present with fever without source, which is a challenging situation in infants <90 days old. The "step-by-step" algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm. METHODS: We performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the "step-by-step" algorithm to 4 clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk (ill-appearing, ≤21 days old, with leukocyturia or procalcitonin level ≥0.5 ng/mL). RESULTS: Among the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but 1 infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill-appearance (72%), an age ≤21 days (27%), or leukocyturia (19%). All these infants had procalcitonin values <0.5 ng/mL and only 1 had C-reactive protein level >20 mg/L. CONCLUSIONS: The "step-by-step" algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants <90 days old.

Neuroinflammatory Disease following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children.

OBJECTIVE: To describe neurologic, radiologic and laboratory features in children with central nervous system (CNS) inflammatory disease complicating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: We focused on CNS inflammatory diseases in children referred from 12 hospitals in the Paris area to Necker-Sick Children Reference Centre. RESULTS: We identified 19 children who had a history of SARS-CoV-2 infection and manifest a variety of CNS inflammatory diseases: encephalopathy, cerebellar ataxia, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, or optic neuritis. All patients had a history of SARS-CoV-2 exposure, and all tested positive for circulating antibodies against SARS-CoV-2. At the onset of the neurologic disease, SARS-CoV-2 PCR results (nasopharyngeal swabs) were positive in 8 children. Cerebrospinal fluid was abnormal in 58% (11/19) and magnetic resonance imaging was abnormal in 74% (14/19). We identified an autoantibody co-trigger in 4 children (myelin-oligodendrocyte and aquaporin 4 antibodies), representing 21% of the cases. No autoantibody was found in the 6 children whose CNS inflammation was accompanied by a multisystem inflammatory syndrome in children. Overall, 89% of patients (17/19) received anti-inflammatory treatment, primarily high-pulse methylprednisolone. All patients had a complete long-term recovery and, to date, no patient with autoantibodies presented with a relapse. CONCLUSIONS: SARS2-CoV-2 represents a new trigger of postinfectious CNS inflammatory diseases in children.

Kingella kingae and Viral Infections.

Kingella kingae (K. kingae) is an oropharyngeal commensal agent of toddlers and the primary cause of osteoarticular infections in 6-23-month-old children. Knowing that the oropharynx of young children is the reservoir and the portal of entry of K. kingae, these results suggested that a viral infection may promote K. kingae infection. In this narrative review, we report the current knowledge of the concomitance between K. kingae and viral infections. This hypothesis was first suggested because some authors described that symptoms of viral infections were frequently concomitant with K. kingae infection. Second, specific viral syndromes, such as hand, foot and mouth disease or stomatitis, have been described in children experiencing a K. kingae infection. Moreover, some clusters of K. kingae infection occurring in daycare centers were preceded by viral outbreaks. Third, the major viruses identified in patients during K. kingae infection were human rhinovirus or coxsackievirus, which both belong to the Picornaviridae family and are known to facilitate bacterial infections. Finally, a temporal association was observed between human rhinovirus circulation and K. kingae infection. Although highly probable, the role of viral infection in the K. kingae pathophysiology remains unclear and is based on case description or temporal association. Molecular studies are needed.

Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children mimicking Kawasaki disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been characterized by high transmission rates and high mortality in adults with predisposing factors, including age>70 years, obesity, diabetes, systemic hypertension and other underlying diseases. During the second week of viral pneumonia, acute respiratory distress syndrome can occur and carries high mortality. Unlike most common respiratory viruses, children seem to be less susceptible to SARS-CoV-2 infection, and generally develop mild disease with low mortality. However, clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes, vasopressors and volume loading have recently been described. Both the clinical symptoms (i.e. high and persistent fever, gastrointestinal disorders, skin rash, conjunctival injection and dry cracked lips) and the biological signs (e.g. elevated C-reactive protein/procalcitonin and high levels of ferritinaemia) mimicked Kawasaki disease. In most cases, intravenous immunoglobin therapy improved cardiac function and led to full recovery within a few days. Adjunctive steroid therapy and sometimes biotherapy (e.g. anti-interleukin 1Ra and anti-interleukin 6 monoclonal antibodies) were often necessary. Although almost all children fully recovered within a week, some of them later developed coronary artery dilation or aneurysm. Thus, a new "multisystem inflammatory syndrome in children" related to SARS-CoV-2 has recently been described. Similarities with Kawasaki disease and the physiopathology of this syndrome still need further exploration.

Rhinovirus: A Narrative Review on Its Genetic Characteristics, Pediatric Clinical Presentations, and Pathogenesis.

Human rhinoviruses (HRVs) are the leading cause of common colds. With the development of new molecular methods since the 2000s, HRVs have been increasingly involved among severe clinical infections. Recent knowledge of the HRV genetic characteristics has also improved the understanding of their pathogenesis. This narrative review aims to provide a current comprehensive knowledge about this virus in the pediatric community. HRVs represent a main cause of upper and lower respiratory tract infections in children. HRV is the second virus involved in bronchiolitis and pneumonia in children, and HRV bronchiolitis has a higher risk of recurrent wheezing episode or asthma. Some recent findings described HRVs in stools, blood, or cerebrospinal fluid, thanks to new molecular techniques such as polymerase chain reaction (PCR) by detecting HRVs with high sensibility. However, the high rate of asymptomatic carriage and the prolonged excretion in postsymptomatic patients complicate interpretation. No sufficient data exist to avoid antibiotic therapy in pediatric high-risk population with HRV detection. Severe clinical presentations due to HRVs can be more frequent in specific population with chronic pathology or genetic particularity. Inflammatory response is mediated by the nuclear factor (NF)-kappa B pathway and production of interferon (IFN)-beta and IFN-gamma, interleukin 8 (IL8), and IL1b. No specific treatment or antiviral therapy exists, although research is still ongoing. Nowadays, in addition to benign diseases, HRVs are recognized to be involved in some severe clinical presentations. Recent advances in genetic knowledge or specific inflammatory response may lead to specific treatment.

SARS-CoV-2 transmission among children and staff in daycare centres during a nationwide lockdown in France: a cross-sectional, multicentre, seroprevalence study.

BACKGROUND: The extent to which very young children contribute to the transmission of SARS-CoV-2 is unclear. We aimed to estimate the seroprevalence of antibodies against SARS-CoV-2 in daycare centres that remained open for key workers' children during a nationwide lockdown in France. METHODS: Children and staff who attended one of 22 daycare centres during a nationwide lockdown in France (between March 15 and May 9, 2020) were included in this cross-sectional, multicentre, seroprevalence study. Hospital staff not occupationally exposed to patients with COVID-19, or to children, were enrolled in a comparator group. The primary outcome was SARS-CoV-2 seroprevalence in children, daycare centre staff, and the comparator group. The presence of antibodies against SARS-CoV-2 in capillary whole blood was measured with a rapid chromatographic immunoassay. We computed raw prevalence as the percentage of individuals with a positive IgG or IgM test, and used Bayesian smoothing to account for imperfect sensitivity and specificity of the assay. This study is registered with ClinicalTrials.gov, NCT04413968. FINDINGS: Between June 4 and July 3, 2020, we enrolled 327 children (mean age 1·9 [SD 0·9] years; range 5 months to 4·4 years), 197 daycare centre staff (mean age 40 [12] years), and 164 adults in the comparator group (42 [12] years). Positive serological tests were observed for 14 children (raw seroprevalence 4·3%; 95% CI 2·6-7·1) and 14 daycare centre staff (7·7%; 4·2-11·6). After accounting for imperfect sensitivity and specificity of the assay, we estimated that 3·7% (95% credible interval [95% CrI] 1·3-6·8) of the children and 6·8% (3·2-11·5) of daycare centre staff had SARS-CoV-2 infection. The comparator group fared similarly to the daycare centre staff; nine participants had a positive serological test (raw seroprevalence 5·5%; 95% CI 2·9-10·1), leading to a seroprevalence of 5·0% (95% CrI 1·6-9·8) after accounting for assay characteristics. An exploratory analysis suggested that seropositive children were more likely than seronegative children to have been exposed to an adult household member with laboratory-confirmed COVID-19 (six [43%] of 14 vs 19 [6%] of 307; relative risk 7·1 [95% CI 2·2-22·4]). INTERPRETATION: According to serological test results, the proportion of young children in our sample with SARS-CoV-2 infection was low. Intrafamily transmission seemed more plausible than transmission within daycare centres. Further epidemiological studies are needed to confirm this exploratory hypothesis. FUNDING: Assistance Publique-Hôpitaux de Paris; Mairie de Paris, Conseil Départemental de Seine Saint Denis. TRANSLATIONS: For the French translation of the abstract see Supplementary Materials section.

Coronavirus Disease 2019 Pandemic: Impact Caused by School Closure and National Lockdown on Pediatric Visits and Admissions for Viral and Nonviral Infections-a Time Series Analysis.

A time series analysis of 871 543 pediatric emergency visits revealed that the coronavirus disease 2019 (COVID-19) lockdown and school closures were associated with a significant decrease in infectious diseases disseminated through airborne or fecal-oral transmission: common cold, gastroenteritis, bronchiolitis, and acute otitis. No change was found for urinary tract infections.

[Multisystemic inflammatory syndrome in children (MIS-C) associated with Covid]. / Syndrome inflammatoire multisystémique associé au Covid chez l'enfant.

Multisystemic inflammatory syndrome in children (mis-c) Asociated with covid Although children are less susceptible to sars-cov-2 and less symptomatic than adults with low mortality, clusters of Septic shock associated with elevated cardiac biomarkers and unusual vasoplegia have been recently described and Treated by inotropes, vasopressors, and fluid loading. Both clinical symptoms (i.e., high and persistent fever, gastrointestinal Disorders, skin rash, conjunctivitis and dry cracked lips) and biological signs (e.g., elevated crp/procalcitonin, high Levels of ferritinemia) resembled kawasaki disease. In most instances, intravenous immunoglobin therapy with glucosteroids Improved the cardiac function and led to full recovery within a few days. However, adjunctive biotherapy (e.g., Anti-il-1ra, anti-il-6 monoclonal antibodies) was sometimes necessary. Although almost all children fully recovered Within a few days, some of them developed late coronary artery dilation or aneurysm. Thus, a new "multisystem inflammatory Syndrome in children" (mis-c) associated with sars-cov-2 has been identified, and its pathophysiology better Understood.

Syndrome inflammatoire multisystémique associé au covid Chez l'enfant Si les enfants apparaissent moins susceptibles au sars-cov-2 et sont moins symptomatiques que les adultes, avec Une faible mortalité, des états de choc associés à une élévation des biomarqueurs cardiaques et à une vasoplégie Inhabituelle, nécessitant un traitement par inotropes, vasopresseurs et un remplissage vasculaire ont été décrits. Les Symptômes cliniques observés (fièvre élevée et durable, troubles digestifs, rash cutané, injection conjonctivale, chéilite) Et le profil biologique (crp/procalcitonine élevées, hyperferritinémie) peuvent parfois mimer un syndrome de kawasaki Atypique. Cette nouvelle entité répond le plus souvent à la perfusion intraveineuse d'immunoglobulines associée à Une corticothérapie, et nécessite parfois une biothérapie anti-il-1ra ou anti-il-6. La majorité des enfants guérit en Quelques jours, avec cependant une possible dilatation des artères coronaires. Ainsi, un nouveau syndrome inflammatoire Multisystémique associé au sars-cov-2 mimant un syndrome de kawasaki a récemment été identifié chez L'enfant et sa physiopathologie est mieux comprise.

Systematic Severe Acute Respiratory Syndrome Coronavirus 2 Screening at Hospital Admission in Children: A French Prospective Multicenter Study.

To assess the relevance of systematic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening of all children admitted to hospital, we conducted a prospective multicenter study including 438 consecutive hospitalized children. A symptom-based SARS-CoV-2 testing strategy failed to identify 45% (95% confidence interval, 24%-68%) of hospitalized children infected by SARS-CoV-2. To limit intrahospital transmission, a systematic screening of children admitted to hospital should be considered.

Changes in Reverse Transcription Polymerase Chain Reaction-positive Severe Acute Respiratory Syndrome Coronavirus 2 Rates in Adults and Children According to the Epidemic Stages.

From March 2, 2020, to April 26, 2020, 52,588 reverse transcription polymerase chain reaction (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were performed in France, 6490 in children and 46,098 in adults. The rate of RT-PCR-positive SARS-CoV-2 tests for children (5.9%) was always less than that for adults (20.3%) but vary according to the epidemic stage. The risk ratio of RT-PCR-positive SARS-CoV-2 tests for adults compared with children was 3.5 (95% confidence interval: 3.2-3.9) for the whole study period.