Pulmonary function using impulse oscillometry system and clinical outcomes at age 4 years in children born extremely preterm with or without bronchopulmonary dysplasia.

This study aimed to describe the early assessment of lung function and respiratory morbidity in children born extremely preterm with or without bronchopulmonary dysplasia (BPD). METHODS: This was a prospective study including all the children born at gestational age ≤28 weeks who received treatment in the NICU of the Centre Intercommunal de Créteil in France, from January 2006 to March 2012. Lung function, using the impulse oscillometry system, respiratory morbidity and growth were assessed at age 4 years. Lung function and clinical course of children were compared in children with and without BPD. RESULTS: We included 136 extremely premature children; 26 (19 %) had BPD. Children with and without BPD did not significantly differ in resistance measurements at 5 Hz (R5) and 20 Hz (R20) and reactance (X5) measurements at age 4 years. A total of 104 (76 %) pre-term children had respiratory resistance R5 above the 95th percentile for the reference population (z-score >1.64), regardless of BPD status. The mean (SD) R5 z-score for all children was 2.1 (±0.7), whereas the mean (SD) R20 was in the normal range (z-score = 1.1 [±0.3]). After treatment with bronchodilators, all children showed no significant change in resistance. The prevalence of asthma symptoms at age 4 years was common and estimated at 30 % regardless of BPD status. CONCLUSION: Early assessment of lung function by the impulse oscillometry system revealed that most preschool children who were born extremely preterm had abnormal total airway resistance regardless of BPD status. The system is an essential tool for the early assessment of children born prematurely.

Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008-2019.

OBJECTIVES: Virulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates. METHODS: Symptomatic infants aged <6 months with a positive B. pertussis culture from 2008-2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 109/L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph. RESULTS: We included 361 infants with pertussis (median age 63 days [interquartile range, 39-86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76-7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06-16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02-19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02-13.83). DISCUSSION: PRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence.

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.

Antimicrobial treatment of lower respiratory tract infections in children.

Lower respiratory tract infections (LRTI) encompass a wide range of clinical syndromes, prominently including bronchiolitis, bronchitis and pneumonia. LRTIs are the second leading cause of antibiotic prescriptions. The vast majority of these infections are due to (or triggered by) viruses and are self-limited diseases. Pneumonia in children is responsible for significant morbidity and mortality worldwide. For clinicians, one of the main difficulties consists in diagnosing pneumonia in febrile children with (or without) cough. The diagnosis is given on the basis of anamnesis, clinical examination and (if necessary) complementary examinations, with chest X-ray or thoracic ultrasound; biological markers are particularly important. Over recent years, since the implementation of PCV13, the bacterial epidemiology of pneumonia and empyema has evolved; involvement in these diseases of pneumococcus has been reduced, and resistance to penicillin has lessened - and remained extremely low. In 2021, according to the National Pneumococcal Reference Center, only 6% of the strains isolated from blood cultures in children are resistant to amoxicillin. The therapeutic choices proposed in this article are in full compliance with the previously published official French recommendations.

The principles of curative antibiotic treatments.

Knowledge of infectious diseases and their treatments is constantly evolving. New infectious agents are regularly discovered, due mainly to improvement of identification techniques, especially the development of molecular biology and mass spectrometry. While changes in the epidemiology of infectious diseases are not always predictable or readily understood, several factors regularly enter into consideration, such as not only the natural history of diseases and the impact of vaccinations, but also the excessive and irrational use of antibiotics. Antibiotic resistance is now recognized as one of the major challenges for humanity, especially since few new molecules have been put on the market in recent years. These molecules are reserved for serious infections caused by bacteria resistant to other antibiotics and should be prescribed only by infectious disease specialists trained in their use. Rationalization of antibiotic therapy is therefore one of the keys to reducing antibiotic resistance and the spread of resistant bacteria. In this guide, with regard to each clinical situation, the bacterial target(s) of antibiotic treatment, the preferred antibiotic choice, and the therapeutic alternatives will be specified. Comments on diagnosis and treatment of the infection will be added if necessary.

Comparison of telerobotic and conventional ultrasonography in children: a crossover bicentric pilot study.

Background: The MELODY system allows for performing ultrasonography on a patient remotely and has been proposed to assess disease characteristics in the context of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this interventional crossover study was to address the feasibility of the system in children aged 1 to 10 years old. Methods: Children underwent ultrasonography with a telerobotic ultrasound system followed by a second conventional examination by a different sonographer. Results: In total, 38 children were enrolled, and 76 examinations were performed, with 76 scans analyzed. The mean [standard deviation (SD)] age of participants was 5.7 (2.7) years (range, 1-10 years). We found substantial agreement between telerobotic and conventional ultrasonography [κ=0.74 (95% CI: 0.53-0.94), P<0.005]. The mean (SD) duration was longer for telerobotic than conventional examinations [26.0 (2.5) vs. 13.9 (11.2) min, P<0.0001]. Abdominal organs and abnormalities were similarly visualized on telerobotic and conventional ultrasonography. Cardiac echocardiography provided reliable diagnoses, with non-significantly different measurements with both techniques, although the visualization score was significantly higher with conventional than telerobotic ultrasonography (P<0.05). On lung analysis, both examinations identified consolidations and pleural effusion, whereas visualization and total lung score were similar with the 2 techniques. Overall, 45% of parents reported that their children felt less pressure with the telerobotic system. Conclusions: Telerobotic ultrasonography may be effective, feasible, and well-tolerated in children.

Meningitis caused by extended-spectrum ß-lactamase-producing Escherichia coli in infants in France: a case series.

Objectives: We report the first case series focusing on clinical and biological characteristics of meningitis caused by ESBL-producing Escherichia coli in infants. Methods: Between 2001 and 2020, data on all cases of E. coli meningitis were prospectively collected from a network of 259 paediatric wards and 168 microbiology laboratories in France. We analysed the clinical and biological characteristics, short-term complications and long-term sequelae of ESBL-producing E. coli meningitis cases in patients <6 months old. Results: In total, 548 cases of E. coli paediatric meningitis were reported. ESBL-producing E. coli represented 12 (2.2%) cases. We included 10 patients aged <6 months old. Eight (80%) patients presented at least one sign of clinical severity: six needed mechanical ventilation, three presented signs of shock and one was in a coma. The overall short-term prognosis was good, with only one meningitis-attributed death in the first hours of care. All surviving children received carbapenems for a median of 21 days (range 9-28). Two relapses occurred, including one in a patient who received only 14 days of imipenem. We reported no long-term sequelae at a median follow-up of 20 months. Conclusions: Meropenem seems to be the treatment of choice for ESBL-producing E. coli meningitis in children and needs to be given as early as possible (<48 h) and for at least 21 days. Maternal colonization or infection with ESBL-producing Enterobacteriaceae needs to be reported to the neonatal or paediatric ICU team, in order to adapt the empirical antibiotic therapy.

Incidence, kinetics, and risk factors for intra- and extracranial cerebral arteriopathies in a newborn sickle cell disease cohort early assessed by transcranial and cervical color Doppler ultrasound.

The risk of stroke in children with sickle cell disease (SCD) is detected by abnormal intracranial arterial time-averaged mean of maximum velocities (TAMVs ≥200 cm/s). Recently, extracranial internal carotid artery (eICA) arteriopathy has been reported, and a cross-sectional study showed that eICA-TAMVs ≥160 cm/s are significantly associated with eICA kinkings and stenosis. The cumulative incidence of and predictive risk factors for intracranial arteriopathy are well described in sickle cell anemia (SCA=SS/Sß0) but are lacking for SC/Sß+ children, as is the cumulative incidence of eICA arteriopathy. We report a prospective longitudinal cohort study including 493 children with SCD (398 SCA, 95 SC/Sß+), all assessed by transcranial and cervical color Doppler ultrasound. Cerebral MRI/MRA data were available in 375 children with SCD and neck MRA in 365 children. eICA kinkings were defined as eICA tortuosities on neck MRA, with an internal acute angle between the two adjacent segments <90°. The median follow-up was 10.6 years. The cumulative incidence of kinkings was significantly lower in SC/Sß+ children than in children with SCA, and no SC/Sß+ child developed intra- or extracranial stenotic arteriopathy. The 10-year KM estimate of cumulative incidence (95% CI) for eICA-TAMVs ≥160 cm/s revealed its development in the 2nd year of life in children with SCA, reaching a plateau of 17.4% (13.2-21.6%) by about 10 years of age, while the plateau for eICA stenosis was 12.3% (8.3-16.3%). eICA assessment identified 13.5% (9.3-17.7%) patients at risk of stroke who were not detected by transcranial color Doppler ultrasound. We also show, for the first time, that in addition to a congenital origin, eICA kinkings sin patients with SCD can develop progressively with aging as a function of eICA-TAMVs, themselves related to anemia severity. Ongoing hydroxyurea treatment was significantly associated with a lower risk of abnormal intracranial arteriopathy and eICA kinkings. After adjustment with hydroxyurea, baseline low hemoglobin, high reticulocyte, and WBC counts remained independent risk factors for intracranial arteriopathy, while low hemoglobin and SEN ß-haplotype number were independent risk factors for extracranial arteriopathy. The association between extracranial arteriopathy and SEN ß-haplotype number suggested a genetic link between the ethnic origin and incidence of eICA kinkings. This prospective cohort study shows the importance of systematically assessing the eICA and of recording biological parameters during the 2nd year of life before any intensive therapy to predict the risk of cerebral arteriopathy and treat patients with severe baseline anemia.

Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France.

Importance: Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown. Objective: To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. Design, Setting, and Participants: This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included. Exposures: PCV13 implementation. Main Outcomes and Measures: Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes. Results: Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period. Conclusions and Relevance: PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

Comparative genomic analysis of ESBL-producing Escherichia coli from faecal carriage and febrile urinary tract infection in children: a prospective multicentre study.

Background: The reliability of ESBL-producing Escherichia coli (ESBL-Ec) faecal carriage monitoring to guide probabilistic treatment of febrile urinary tract infection (FUTI) in children remains unclear. Objectives: To compare the genomic characteristics of ESBL-Ec isolates from faecal carriage and FUTI to assess their correlation and identify a FUTI-associated virulence profile. Methods: We conducted a prospective multicentre hospital and ambulatory-based study. We analysed the genotypes and virulence factors of both faecal and FUTI ESBL-Ec by whole genome sequencing. Correlations were assessed by non-parametric Spearman coefficient and virulence factors were assessed by chi-squared tests with Bonferroni correction. Results: We included 218 ESBL-Ec causing FUTI and 154 ESBL-Ec faecal carriage isolates. The most frequent ST was ST131 (44%) in both collections. We found high correlation between carriage and ESBL-Ec FUTI regarding genes/alleles (rho = 0.88, P < 0.0001) and combinations of virulence genes, MLST and serotypes (rho = 0.90, P < 0.0001, rho = 0.99, P = 0.0003, rho = 0.97, P = 0.005 respectively). Beside this strong correlation, we found five genes that were significantly associated with FUTI (papC, papGII, hlyC, hek and traJ). The strongest association with FUTI was found with adhesin gene allele papGII (54% in FUTI versus 16% in carriage) and for papGII and gene traJ alone or in combination (63% versus 24%). Conclusions: The genomic profile of ESBL-Ec causing FUTI in children strongly correlates with faecal carriage isolates except for a few genes. The presence of papGII and/or traJ in a previously identified carriage strain could be used as a marker of uropathogenicity and may guide the empirical antimicrobial choice in subsequent FUTI.

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.

Relay oral therapy in febrile urinary tract infections caused by extended spectrum beta-lactamase-producing Enterobacteriaceae in children: A French multicenter study.

OBJECTIVES: We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL-producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used. MATERIALS AND METHODS: We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved. RESULTS: We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination. CONCLUSIONS: The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin.

Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections.

OBJECTIVES: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of ß-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. MATERIALS AND METHODS: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of ß-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. RESULTS: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant ß-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). CONCLUSIONS: Despite the frequent association of ESBL genes with inhibitor-resistant ß-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

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.

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.