Treatment of Resistant Gram-negative bacilli in children.

Resistance of Gram-negative bacteria to the most widely used antibiotics, particularly ß-lactams, is now considered as major public health problem. The main resistance mechanisms to ß-lactams in Enterobacterales are the production of extended spectrum ß-lactamases (ESBL) or carbapenemases, which hydrolyze virtually all ß-lactams. However, a substantial proportion of carbapenem-resistant Gram-negative bacilli do not produce carbapenemase but combine overproduction of a cephalosporinase and/or ESBL with very low penem hydrolysis and reduced outer membrane permeability. The arrival of new antibacterial agents active on some of these multidrug-resistant strains, such as new ß-lactam inhibitors, has marked a turning point in treatment and represents real progress. In-depth knowledge of resistance mechanisms is crucial to the choice of the most effective molecule, and their prescription requires close collaboration between microbiologists, infectious disease specialists and intensive care physicians. While these compounds are significantly more active against resistant strains than those previously available, their spectrum of activity does not cover all resistance mechanisms in Gram-negatives, nor in other bacterial species potentially involved in polymicrobial infections. The use of these new compounds does not alter antibiotic regimens in terms of duration and indication of combined antibiotic therapy, which remain very limited.

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 skin and soft tissue infections.

Bacterial skin infections are common in children, and frequently do not require systemic antibiotic therapy, particularly for superficial forms. In these cases, washing (with soap and water) and careful rinsing of the lesion are the key points of treatment. A semiotic analysis must precede any therapeutic decision to assess the appropriateness of antibiotic therapy, need for drainage (which may be spontaneous or surgical) and possible existence of symptoms related to toxin production, which are frequent signs of severity. The bacterial species most frequently implicated in children are Staphylococcus aureus and Streptococcus pyogenes. Given the low incidence of methicillin-resistant S. aureus in France (<10%), the first-line antibiotic treatment is amoxicillin-clavulanate, to which an anti-toxin treatment such as clindamycin may be added for patients with overt toxin signs.

[Epidemiology and the burden of RSV]. / Épidémiologie et fardeau du VRS.

RSV is an almost obligatory virus responsible for upper (rhinitis and otitis) and lower (bronchiolitis and asthma attack) respiratory infections in children under 5 years of age. Reinfections are frequent at all ages because immunity is only partial and does not last long. Young children under the age of 1 are the most affected. The majority of these children are healthy. Having a risk factor (premature birth, heart disease, bronchopulmonary dysplasia, but also passive smoking) increases the severity of RSV pathology. Very few children currently benefit from prevention by anti-RSV monoclonal antibodies. The annual cost of care, the various socio-economic costs are a public health reality in three care sectors: out-patient, pediatric emergencies, hospitalization. Subsequent consequences: repeated wheezing and asthma, should also be taken into consideration and integrated into public health decisions. Progress in recognizing this pathology is desirable: distribution of diagnostic tests in the city; providing parents with information.

Le VRS est un virus quasi obligatoire responsable d'infections respiratoires hautes (rhinite et otite) et basses (bronchiolite et crise d'asthme) chez l'enfant de moins de 5 ans. Les réinfections sont fréquentes du fait d'une immunité partielle, peu durable, à tous les âges de la vie. Les jeunes enfants de moins de 1 an sont les plus touchés. La majorité de ces enfants sont bien portants. Avoir un facteur de risque (prématurité, cardiopathie, dysplasie bronchopulmonaire mais aussi tabagisme passif) majore la sévérité de la pathologie à VRS. Très peu d'enfants bénéficient actuellement d'une prévention par les anticorps monoclonaux anti-VRS. La charge annuelle en soins, les coûts socioéconomiques variés constituent une réalité de santé publique portant sur les trois secteurs de soins : ambulatoire, urgences pédiatriques, hospitalisation.Les conséquences ultérieures : répétition de wheezing, asthme, devraient aussi être pris en considération et intégrés dans les décisions de santé publique.Des progrès dans la reconnaissance de cette pathologie sont souhaitables : diffusion des tests diagnostiques en ville ; information aux parents.

Procalcitonin at 12-36 hours of fever for prediction of invasive bacterial infections in hospitalized febrile neonates.

Aim: We aimed to investigate the performance of procalcitonin (PCT) assay between 12 and 36 h after onset of fever (PCT H12-H36) to predict invasive bacterial infection (IBI) (ie, meningitis and/or bacteremia) in febrile neonates. Methods: We retrospectively included all febrile neonates hospitalized in the general pediatric department in a teaching hospital from January 2013 to December 2019. PCT assay ≤ 0.6 ng/ml was defined as negative. The primary outcome was to study the performance of PCT H12-H36 to predict IBI. Results: Out of 385 included neonates, IBI was ascertainable for 357 neonates (92.7%). We found 16 IBI: 3 meningitis and 13 bacteremia. Sensitivity and specificity of PCT H12-H36 in the identification of IBI were, respectively, 100% [95% CI 82.9-100%] and 71.8% [95% CI 66.8-76.6%], with positive and negative predictive values of 14.3% [95% CI 8.4-22.2%] and 100% [95% CI 98.8-100%] respectively. Of the 259 neonates who had a PCT assay within the first 12 h of fever (< H12) and a PCT assay after H12-H36, 8 had IBI. Two of these 8 neonates had a negative < H12 PCT but a positive H12-H36 PCT. Conclusions: PCT H12-H36 did not miss any IBI whereas < H12 PCT could missed IBI diagnoses. PCT H12-H36 might be included in clinical decision rule to help physicians to stop early antibiotics in febrile neonates.

Retrospective observational study of the influence of the COVID-19 outbreak on infants' hospitalisation for acute bronchiolitis.

OBJECTIVES: Acute bronchiolitis is a major public health issue with high number of infants hospitalised worldwide each year. In France, hospitalisations mostly occur between October and March and peak in December. A reduction of emergency visits for bronchiolitis has been observed at onset of the COVID-19 outbreak. We aimed to assess the pandemic effects on the hospitalisations for bronchiolitis during the 2020-2021 winter (COVID-19 period) compared with three previous winters (pre-COVID-19). DESIGN: Retrospective, observational and cross-sectional study. SETTING: Tertiary university paediatric hospital in Paris (France). PARTICIPANTS: All infants aged under 12 months who were hospitalised for acute bronchiolitis during the autumn/winter seasons (1 October to 31 March) from 2017 to 2021 were included. Clinical and laboratory data were collected using standardised forms. RESULTS: During the COVID-19 period was observed, a 54.3% reduction in hospitalisations for bronchiolitis associated with a delayed peak (February instead of November-December). Clinical characteristics and hospitalisation courses were substantially similar. The differences during the COVID-19 period were: smaller proportion of infants with comorbidities (8% vs 14% p=0.02), lower need for oxygen (45% vs 55%, p=0.01), higher proportions of metapneumovirus, parainfluenzae 3, bocavirus, coronavirus NL63 and OC43 (all p≤0.01) and no influenza. The three infants positive for SARS-CoV-2 were also positive for respiratory syncytial virus, suggesting that SARS-CoV-2 alone does not cause bronchiolitis, despite previous assumptions. CONCLUSION: The dramatic reduction in infants' hospitalisations for acute bronchiolitis is an opportunity to change our future habits such as advising the population to wear masks and apply additional hygiene measures in case of respiratory tract infections. This may change the worldwide bronchiolitis burden and improve children respiratory outcomes.

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.

Shift in Clinical Profile of Hospitalized Pneumonia in Children in the Non-pharmaceutical Interventions Period During the COVID-19 Pandemic: A Prospective Multicenter Study.

Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 were implemented in March 2020. These measures were followed by a major impact on viral and non-viral diseases. We aimed to assess the impact of NPI implementation in France on hospitalized community-acquired pneumonia (hCAP) frequency and the clinical and biological characteristics of the remaining cases in children. We performed a quasi-experimental interrupted time-series analysis. Between June 2014 and December 2020, eight pediatric emergency departments throughout France reported prospectively all cases of hCAP in children from age 1 month to 15 years. We estimated the impact on the monthly number of hCAP using segmented linear regression with autoregressive error model. We included 2,972 hCAP cases; 115 occurred during the NPI implementation period. We observed a sharp decrease in the monthly number of hCAP after NPI implementation [-63.0% (95 confidence interval, -86.8 to -39.2%); p < 0.001]. Children with hCAP were significantly older during than before the NPI period (median age, 3.9 vs. 2.3 years; p < 0.0001), and we observed a higher proportion of low inflammatory marker status (43.5 vs. 33.1%; p = 0.02). Furthermore, we observed a trend with a decrease in the proportion of cases with pleural effusion (5.3% during the NPI period vs. 10.9% before the NPI; p = 0.06). NPI implementation during the COVID-19 (coronavirus disease 2019) pandemic led not only to a strong decrease in the number of hCAP cases but also a modification in the clinical profile of children affected, which may reflect a change in pathogens involved.

Educational Setting and SARS-CoV-2 Transmission Among Children With Multisystem Inflammatory Syndrome: A French National Surveillance System.

Background: Multisystem inflammatory syndrome in children (MIS-C) is the most severe form associated with SARS-CoV-2 infection in children. To reduce the spread of SARS-CoV-2 at the population level, educational setting closure have been implemented in many countries. However, the direct benefit of school closure on the MIS-C burden remains to be explored. We aimed to assess the role of educational settings in SARS-CoV-2 transmission among children with MIS-C. Methods: We conducted a French national prospective surveillance of MIS-C, coordinated by Public Health France, from April 2020 to March 2021. During this period, we included all children with MIS-C fulfilling the WHO definition who were reported to Public Health France. For each child, we traced the source of SARS-CoV-2 transmission. The main outcome was the proportion of children with MIS-C, with educational setting-related SARS-CoV-2 infection, during the period of school opening. Results: We included 142 children fulfilling WHO criteria for MIS-C: 104 (70%) cases occurred during school opening periods. In total, 62/104 children (60%, 95%CI [50; 69]) had been contaminated by a household contact and 5/104 in educational settings (5%, 95%CI [2; 11]). Among children with MIS-C occurring during school closure periods, the proportion of household transmission remained similar (66%, 25/38). Conclusion: Children with MIS-C were mainly infected by SARS-CoV-2 within their family environment, and the educational setting played a marginal role in this transmission. This suggests that mitigating school attendance may not reduce substantially the burden of MIS-C.

A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. METHODS: To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. FINDINGS: The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. CONCLUSIONS: These results provide potential for a better understanding of disease pathophysiology. FUNDING: Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d'Excellence ''Milieu Intérieur," grant ANR-10-LABX-69-01; ANR-flash Covid19 "AIROCovid" and "CoVarImm"), Institut National de la Santé et de la Recherche Médicale (INSERM), and the "URGENCE COVID-19" fundraising campaign of Institut Pasteur.

Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020.

BackgroundChildren have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections.AimWe tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection.MethodsWe set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections.ResultsPrevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children.ConclusionPrior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

Acute monoarthritis in young children: comparing the characteristics of patients with juvenile idiopathic arthritis versus septic and undifferentiated arthritis.

Acute arthritis is a common cause of consultation in pediatric emergency wards. Arthritis can be caused by juvenile idiopathic arthritis (JIA), septic (SA) or remain undetermined (UA). In young children, SA is mainly caused by Kingella kingae (KK), a hard to grow bacteria leading generally to a mild clinical and biological form of SA. An early accurate diagnosis between KK-SA and early-onset JIA is essential to provide appropriate treatment and follow-up. The aim of this work was to compare clinical and biological characteristics, length of hospital stays, duration of intravenous (IV) antibiotics exposure and use of invasive surgical management of patients under 6 years of age hospitalized for acute monoarthritis with a final diagnosis of JIA, SA or UA. We retrospectively analyzed data from < 6-year-old children, hospitalized at a French tertiary center for acute mono-arthritis, who underwent a joint aspiration. Non-parametric tests were performed to compare children with JIA, SA or UA. Bonferroni correction for multiple comparisons was applied with threshold for significance at 0.025. Among the 196 included patients, 110 (56.1%) had SA, 20 (10.2%) had JIA and 66 (33.7%) had UA. Patients with JIA were older when compared to SA (2.7 years [1.8-3.6] versus 1.4 [1.1-2.1], p < 0.001). Presence of fever was not different between JIA and SA or UA. White blood cells in serum were lower in JIA (11.2 × 109/L [10-13.6]) when compared to SA (13.2 × 109/L [11-16.6]), p = 0.01. In synovial fluid leucocytes were higher in SA 105.5 × 103 cells/mm3 [46-211] compared to JIA and UA (42 × 103 cells/mm3 [6.4-59.2] and 7.29 × 103 cells/mm3 [2.1-72] respectively), p < 0.001. Intravenous antibiotics were administered to 95% of children with JIA, 100% of patients with SA, and 95.4% of UA. Arthrotomy-lavage was performed in 66.7% of patients with JIA, 79.6% of patients with SA, and 71.1% of patients with UA. In children less than 6 years of age with acute mono-arthritis, the clinical and biological parameters currently used do not reliably differentiate between JIA, AS and UA. JIA subgroups that present a diagnostic problem at the onset of monoarthritis before the age of 6 years, are oligoarticular JIA and systemic JIA with hip arthritis. The development of new biomarkers will be required to distinguish JIA and AS caused by Kingella kingae in these patients.

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.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

Factors Associated With Severe SARS-CoV-2 Infection.

BACKGROUND: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution. METHODS: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement. RESULTS: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children <90 days old accounted for 37% of cases (145 of 397), but only 4 (3%) had severe disease. Excluding children with multisystem inflammatory syndrome in children (n = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 (n = 62), 23 of 306 (11%) children had severe disease, including 6 deaths. Factors independently associated with severity were age ≥10 years (odds ratio [OR] = 3.4, 95% confidence interval: 1.1-10.3), hypoxemia (OR = 8.9 [2.6-29.7]), C-reactive protein level ≥80 mg/L (OR = 6.6 [1.4-27.5]). CONCLUSIONS: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution. This may help physicians to better identify risk of severe disease progression in children.

Multisystem inflammatory syndrome in children rose and fell with the first wave of the COVID-19 pandemic in France.

AIM: This study determined the influence of the COVID-19 pandemic on the occurrence of multisystem inflammatory syndrome in children (MIS-C) and compared the main characteristics of MIS-C and Kawasaki disease (KD). METHODS: We included patients aged up to 18 years of age who were diagnosed with MIS-C or KD in a paediatric university hospital in Paris from 1 January 2018 to 15 July 2020. Clinical, laboratory and imaging characteristics were compared, and new French COVID-19 cases were correlated with MIS-C cases in our hospital. RESULTS: There were seven children with MIS-C, from 6 months to 12 years of age, who were all positive for the virus that causes COVID-19, and 40 virus-negative children with KD. Their respective characteristics were as follows: under 5 years of age (14.3% vs. 85.0%), paediatric intensive care unit admission (100% vs. 10.0%), abdominal pain (71.4% vs. 12.5%), myocardial dysfunction (85.7% vs. 5.0%), shock syndrome (85.7% vs. 2.5%) and mean and standard deviation C-reactive protein (339 ± 131 vs. 153 ± 87). There was a strong lagged correlation between the rise and fall in MIS-C patients and COVID-19 cases. CONCLUSION: The rise and fall of COVID-19 first wave mirrored the MIS-C cases. There were important differences between MIS-C and KD.

International consensus validation of the POPI tool (Pediatrics: Omission of Prescriptions and Inappropriate prescriptions) to identify inappropriate prescribing in pediatrics.

INTRODUCTION: While drug prescription should be based on established recommendations stemming from clinical trials but in pediatrics, many drugs are used without marketing authorization. Consequently recommendations are often based on clinical experience and the risk of inappropriate prescription (IP) is high. A tool for detecting IP in pediatrics-called POPI (Pediatrics: Omission of Prescriptions and Inappropriate prescriptions)-has been developed in France. However the relevance of its use at an international level is not known. Our aim has been to adapt POPI for a worldwide use. MATERIAL AND METHOD: A two-round Delphi online questionnaire was completed and validated by international experts to identify consensual items. They were asked to rate the validity of each items taking into account the recommendations and practices in their countries. Only propositions obtaining a median score in the upper tertile with an agreement of more than 75% of the panel-for the first round-and 85%-for the second round-were retained. RESULTS: Our panel included 11 pharmacists (55%) and 9 physicians (45%). The panelists came from 12 different countries: England, Belgium, Brazil, Canada, China, Ivory Coast, Ireland, Malaysia, Portugal, Switzerland, Turkey and Vietnam. At the end of the first round, of the 105 items of the original POPI tool, 80 items were retained including 16 items reworded and 25 items were deleted. In the second round, 14 experts participated in the study. This final international POPI tool is composed of 73 IP and omissions of prescriptions in the fields of neuropsychiatry, dermatology, infectiology, pneumology, gastroenterology, pain and fever. DISCUSSION AND CONCLUSION: This study highlights international consensus on prescription practice in pediatrics. The use of this tool in everyday practice could reduce the risk of inappropriate prescription. The impact of the diffusion of POPI tool will be assessed in a prospective multicentric study.

Cardiac MRI in Children with Multisystem Inflammatory Syndrome Associated with COVID-19.

This case series examines cardiac MRI findings in four children and adolescents admitted to intensive care in April 2020 for multisystem inflammatory syndrome and Kawasaki disease-like features related to coronavirus disease 2019 (COVID-19). Acute myocarditis occurred less than 1 week after onset of fever and gastrointestinal symptoms. Physical examination showed rash and cheilitis or conjunctivitis. All patients recovered after intravenous immunoglobulin therapy. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction was negative in nasopharyngeal, stool, and respiratory samples and was positive on serology. Cardiac MRI showed diffuse myocardial edema on T2 short tau inversion-recovery sequences and native T1 mapping, with no evidence of late gadolinium enhancement suggestive of replacement fibrosis or focal necrosis. These findings favor postinfectious myocarditis in children and adolescents with COVID-19.