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Objective: To study the impact of nonpharmaceutical interventions implemented during the COVID-19 pandemic on the monthly incidence of sudden unexpected death in infancy (SUDI) cases overall and those with a viral or bacterial identification., Study Design: We conducted an interrupted time-series analysis using seasonally adjusted Poisson regression models from the French national prospective and multicenter SUDI registry, that included all SUDI cases below the age of 1 year who died from 2016 to 2021 in mainland France., Results: Of 998 SUDI cases analyzed, 750 were recorded during the prepandemic period (January 2016 through March 2020) and 248 during the NPI period (April 2020 through December 2021). We found a significant seasonal pattern of overall monthly SUDI incidence, with a peak observed periodically from November to February. The monthly SUDI incidence decreased significantly from the prepandemic to NPI periods (adjusted incidence rate ratio 0.83 [95% CI 0.72-0.96]). In particular, the monthly incidence of SUDI cases with a viral or bacterial identification decreased significantly, while no significant difference was found for SUDI cases without a viral or bacterial identification., Conclusions: Nonpharmaceutical interventions were associated with a significant change in the incidence of SUDI cases with a viral or bacterial identification. Further investigations are needed to analyze the pathophysiologic role of viruses and bacteria in the SUDI., Competing Interests: Declaration of Competing Interest The French SUDI registry receives main funding from AXA, France; MSDAvenir, France; Sanofi Pasteur-MSD, France; the French national public health agency (Santé Publique France), France; the National Institute of Health and Medical Research (Inserm), France; and 3 French parent associations (SA VIE, Naitre et Vivre, and Les Rires d'Anna); it also received gifts from private organizations and companies. This particular work was supported by the Fondation de France (Alliance “Tous unis contre le virus”, grant n°APHP220322). Funders were not involved in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. No support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work, and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to describe cases of acute bacterial meningitis (ABM) without cerebrospinal fluid (CSF) pleocytosis and the clinical and biological characteristics of affected children., Methods: We analyzed results of a nation-wide population-based prospective surveillance study of acute ABM in children aged 3 months to 15 years in France. Absence of CSF pleocytosis was defined as CSF leukocyte count ≤5/mm 3 ., Results: We included 4754 cases of acute ABM from 2001 to 2022: 173 patients (3.6%) did not have CSF pleocytosis. ABM cases without CSF pleocytosis were mainly related to meningococcus (70% vs 44% with CSF pleocytosis, P <0.001). When performed in CSF with normal leukocyte count, Gram staining results were positive for 33%, culture for 80%, polymerase chain reaction results for 41%, and antigen detection for 20% of cases. Case fatality rate was higher for cases without than those with CSF pleocytosis (18% vs 6%, P <0.001). On multivariate analysis, absence of CSF pleocytosis was associated only with seizures before hospital arrival (adjusted odds ratio 2.3, 95% confidence interval 1.2-4.6, P <0.01)., Conclusions: ABM without CSF pleocytosis is infrequent but not exceptional, particularly in children with seizures before hospital arrival. Extended vaccination against meningococcus could prevent this clinical form with a high case fatality rate., Competing Interests: Declarations of competing interest Corinne Levy received grants from Pfizer during the conduct of the study, personal fees from Pfizer and MSD, and nonfinancial support from Pfizer outside the submitted work. Emmanuelle Varon received grants from the French Public Health Agency during the conduct of the study, and from Pfizer and MSD outside the submitted work. Muhamed Kheir Taha performs contract work for the Institut Pasteur funded by GSK, Pfizer, and Sanofi Pasteur, and has a patent with GSK (“Vaccines for serogroup X meningococcus”; NZ630133A Patent). Naïm Ouldali received grants from Pfizer to his institution during the conduct of the study and travel grants from Pfizer, Sanofi, and GlaxoSmithKline outside the submitted work. François Angoulvant received personal fees from MSD, Sanofi, and AstraZeneca outside the submitted work. Robert Cohen received personal fees from Sanofi, Pfizer, MSD, Viatris, and GSK; travel grants from Sanofi, Pfizer, and MSD; and grants from Sanofi, Pfizer, MSD, and GSK outside the submitted work. Alexis Rybak received personal fees from MSD and Pfizer outside the submitted work and nonfinancial support from Pfizer and AstraZeneca. The remaining authors report no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: Mental disorders among the pediatric population are a major area of public health concern. Little is known regarding changes in pediatric hospital resource use related to mental health (MH) long after the onset of the COVID-19 pandemic in March 2020., Objective: To assess rates and trends of hospitalizations and emergency department (ED) visits related to MH and self-harm (SH) among children before and during the 3 years following the pandemic onset., Design, Setting, and Participants: This cross-sectional study used national hospital data. The study sample included all MH- and SH-related hospitalizations and ED visits among children aged 6 to 17 years in France between January 1, 2016, to May 31, 2023., Main Outcomes and Measures: Interrupted time-series analysis of monthly rates of MH- and SH-related hospitalizations and ED visits per 100 000 children was conducted to assess changes before and every year after the pandemic onset. Rate ratios (RRs) between estimated and expected rates were calculated., Results: Overall, 583 244 hospitalizations (81.4% for MH and 18.6% for SH) and 432 725 ED visits (79.9% for MH and 20.1% for SH) were analyzed. The mean (SD) age of the children was 13.7 (2.9) and 14.8 (1.7) years for MH-related and SH-related hospitalizations, respectively, and 14.2 (2.6) and 14.6 (2.1) years for MH-related and SH-related ED visits, respectively. For MH-related hospitalizations, 52.6% were female and 47.4% were male; for SH-related hospitalizations, 83.1% were female and 16.9% were male. For MH-related ED visits, 62.8% were female and 37.2% were male; for SH-related ED visits, 77.4% were female and 22.6% were male. Before the pandemic, an increasing trend in all monthly rates, except that of MH-related hospitalizations, was observed. After an immediate decrease in hospitalization and ED visit rates during the initial pandemic period (March 1 to May 31, 2020), trends increased in the first 2 years following the pandemic onset and decreased thereafter. Overall, rates of MH-related hospitalizations and ED visits exceeded expected rates in only the second year after the pandemic onset, with increases of 6.0% (RR, 1.06 [95% CI, 1.05-1.06]) and 5.0% (RR, 1.05 [95% CI, 1.04-1.05]), respectively. However, rates of hospitalizations and ED visits for behavioral syndromes (mainly eating and sleeping disorders) persistently exceeded expected rates, with increases of 29.0% (RR, 1.29 [95% CI, 1.25-1.34]) and 26.0% (RR, 1.26 [95% CI, 1.21-1.31]) in the third year, respectively. Likewise, rates of SH-related hospitalizations and ED visits persistently rose above expected rates, with increases of 29.0% (RR, 1.29 [95% CI, 1.26-1.32]) and 43.0% (RR, 1.43 [95% CI, 1.40-1.47]) in the third year, respectively., Conclusions and Relevance: In this cross-sectional study, persistent increases in the use of hospital resources to treat eating and sleeping disorders and intentional SH among pediatric patients were observed long after the onset of the COVID-19 pandemic. These findings warrant future research to identify persistent stress factors in children.

Competing Interests: JP reports research grants from Merck and MedImmune and personal fees from AstraZeneca and Merck. NO is funded by the 2023 ATIP–Avenir partnership between the French National Institute for Health and Medical Research and the French National Center for Scientific Research and reports travel grants from GlaxoSmithKline, Pfizer, MSD, and Sanofi. ZA declares no competing interests.

The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-reactive CD3 + CD4 + CD154 + T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4 + T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4 + T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2-reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.

Background: Respiratory syncytial virus (RSV) is the leading cause of lower-respiratory-tract infection in children. Nirsevimab, a monoclonal antibody against RSV, was implemented in a few countries in September 2023. However, its post-license effectiveness in ambulatory care settings is unknown. We aimed to assess the effectiveness of nirsevimab against RSV-bronchiolitis in outpatients aged <12 months., Methods: We conducted a test-negative case-control study based on a national ambulatory surveillance system. We included all infants aged <12 months who had bronchiolitis and results of an RSV rapid antigen test performed, visiting a network of 107 ambulatory paediatricians from September 15, 2023, to February 1, 2024. Case patients were infants with bronchiolitis and a rapid antigen test positive for RSV. Control patients were infants with bronchiolitis and a rapid antigen test negative for RSV. Effectiveness was assessed by a logistic regression model adjusted for potential confounders. A range of sensitivity analyses were conducted to assess the robustness of the findings., Findings: We included 883 outpatients who had bronchiolitis and results of an RSV rapid antigen test (453 were case patients, and 430 were control patients). Overall, 62/453 (13.7%) case patients and 177/430 (41.2%) control patients had been previously immunised for nirsevimab. The adjusted effectiveness of nirsevimab against RSV-bronchiolitis was 79.7% (95% CI 67.7-87.3). Sensitivity analyses gave similar results., Interpretation: This post-license study indicates that nirsevimab was effective in preventing RSV-bronchiolitis in ambulatory care settings., Funding: The study was supported by Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), French Pediatrician Ambulatory Association (AFPA) and unrestricted grants from GSK, MSD, Pfizer and Sanofi., Competing Interests: YL has no conflicts of interest to disclose. RB declares receiving fees from Sanofi and MSD for medical conferences or scientific meetings. CL declares receiving travel grants from MSD, Pfizer and fees from MSD and Pfizer for scientific meetings and expert board participation. AW declares receiving fees from Sanofi, GSK and MSD for medical conferences or scientific meetings. FCS declares receiving fees from Sanofi for expert board participation. CB declares receiving fees from Sanofi, GSK and MSD for medical conferences or scientific meetings. RC reports personal fees and non-financial support from Pfizer and personal fees from GSK, Merck, Pfizer, Sanofi, Viatris outside the submitted work. NO declares receiving travel grants from MSD, Pfizer, Sanofi, and GSK., (© 2024 The Authors.)

Background: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear., Methods: We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed., Results: The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%])., Conclusions: In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.)., (Copyright © 2024 Massachusetts Medical Society.)

Using multiple national surveillance systems, we found an increase in the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage., Competing Interests: Potential conflicts of interest . A. R. reports nonfinancial support from Pfizer and AstraZeneca; consulting fees from Sanofi (board paid by Sanofi); and payment or honoraria for presentations paid by MSD. C. L. reports grants from Pfizer during the conduct of the study; personal fees from Pfizer and MSD; nonfinancial support from Pfizer; grants or contracts from GlaxoSmithKline (GSK), MSD, Pfizer, and Sanofi (payment to ACTIV); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD; participation on a data safety monitoring board or advisory board for MSD and support for attending meetings and/or travel from Pfizer, outside the submitted work. S. Béchet reports grants or contracts from GSK, MSD, Pfizer, and Sanofi paid to ACTIV, outside the submitted work. A. Werner reports all of the following from Sanofi, MSD, GSK, and Pfizer: consulting fees, paid to the author and institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, to the author and institution; payment for expert testimony, to the author and institution; support for attending meetings and/or travel, to the author; and participation on a data safety monitoring board or advisory board. F. A. reports receiving personal fees from MSD, Sanofi, and AstraZeneca and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sanofi, paid to the institution Centre hospitalier universitaire vaudois (CHUV), and from MSD and Pfizer, paid to the author, outside the submitted work. R. C. reports receiving personal fees from Sanofi, Pfizer, MSD, Viatris and GSK; travel grants from Pfizer and MSD; grants from Sanofi, Pfizer, MSD, and GSK; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, paid to the author; participation on a data safety monitoring board or advisory board for Pfizer, Sanofi, MSD, and GSK; and payment for expert testimony from Pfizer and MSD, outside the submitted work. E. V. reports grants from the French public health agency, paid to the institution; grants from Pfizer and from MSD; payment for expert testimony from Pfizer and MSD, paid to the institution; and support for attending meetings and/or travel from Pfizer, outside the submitted work. N. O. reports receiving grants from Pfizer to his institution during the conduct of the study and travel grants from Pfizer, Sanofi, and GSK, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis., Methods: This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis., Results: Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity., Conclusion: Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Multisystem inflammatory syndrome in children (MIS-C or PIMS-TS) is a severe disease. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used for positive and differential diagnosis, diagnosis of complications and severity, and cardiogenic shock prediction. However, contrasting cut-offs have been suggested. The aims of the present study were to compare NT-proBNP values depending on the time of measurement and to describe the NT-proBNP course during the MIS-C episode. The data from a single-centre cohort observational study on the impact of time to diagnosis, defined as the time from first symptom to diagnosis of MIS-C, were used for the purpose of this study, with an extended period of inclusion from May 2020 to April 2023. The timing and level of all NT-proBNP samples available for each patient were retrospectively collected. Thirty-seven children (18 (49%) females, median age 8.8 years, 14 (38%) with shock) were included. Until diagnosis, NT-proBNP increased with time and was significantly higher at 6 days from first symptoms than at 3 days (median (interquartile range) 32,933 (7773-61,592) versus 1994 (1291-4190) pg/mL, respectively, p = 0.031). From diagnosis, NT-proBNP decreased by at least 50% after 3.0 (2.1-5.3) days (n = 12) when NT-proBNP at diagnosis was low ≤ 11,000 pg/mL versus 1.8 (0.7-3.4) days (n = 16) when NT-proBNP at diagnosis was high (p = 0.040), and after 3.6 (2.4-5.9) days (n = 7) when fever persisted after 48 h versus 1.8 (0.8-3.0) days (n = 21) when fever resolved before 48 h (p = 0.004).  Conclusions: During the MIS-C episode, NT-proBNP increased over time until diagnosis and treatment. It dropped faster thereafter in children with high NT-proBNP at diagnosis > 11,000 pg/mL and slower in case of persistent fever. What is Known: • NT-proBNP is useful in MIS-C for positive and differential diagnosis, diagnosis of complications and severity, and cardiogenic shock prediction. • Contrasting cut-offs for differential diagnosis and severity assessment have been suggested. What is New: • Before diagnosis, NT-proBNP increases with time and is significantly higher at 6 days from first symptoms than at 3 days suggesting different cut-offs depending on the timing of measurement. • From diagnosis and treatment initiation, the 50% NT-proBNP drop occurs earlier in children with high NT-proBNP at diagnosis > 11,000 pg/mL and later in children with persistent fever., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Numerous studies have provided evidence for the negative associations of the COVID-19 pandemic with mental health, but data on the use of psychotropic medication in children and adolescents after the onset of the COVID-19 pandemic are lacking., Objective: To assess the rates and trends of psychotropic medication prescribing before and over the 2 years after the onset of the COVID-19 pandemic in children and adolescents in France., Design, Setting, and Participants: This cross-sectional study used nationwide interrupted time-series analysis of outpatient drug dispensing data from the IQVIA X-ponent database. All 8 839 143 psychotropic medication prescriptions dispensed to children (6 to 11 years of age) and adolescents (12 to 17 years of age) between January 2016 and May 2022 in France were retrieved and analyzed., Exposure: Onset of COVID-19 pandemic., Main Outcomes and Measures: Monthly rates of psychotropic medication prescriptions per 1000 children and adolescents were analyzed using a quasi-Poisson regression before and after the pandemic onset (March 2020), and percentage changes in rates and trends were assessed. After the pandemic onset, rate ratios (RRs) were calculated between estimated and expected monthly prescription rates. Analyses were stratified by psychotropic medication class (antipsychotic, anxiolytic, hypnotic and sedative, antidepressant, and psychostimulant) and age group (children, adolescents)., Results: In total, 8 839 143 psychotropic medication prescriptions were analyzed, 5 884 819 [66.6%] for adolescents and 2 954 324 [33.4%] for children. In January 2016, the estimated rate of monthly psychotropic medication prescriptions was 9.9 per 1000 children and adolescents, with the prepandemic rate increasing by 0.4% per month (95% CI, 0.3%-0.4%). In March 2020, the monthly prescription rate dropped by 11.5% (95% CI, -17.7% to -4.9%). During the 2 years following the pandemic onset, the trend changed significantly, and the prescription rate increased by 1.3% per month (95% CI, 1.2%-1.5%), reaching 16.1 per 1000 children and adolescents in May 2022. Monthly rates of psychotropic medication prescriptions exceeded the expected rates by 11% (RR, 1.11 [95% CI, 1.08-1.14]). Increases in prescribing trends were observed for all psychotropic medication classes after the pandemic onset but were substantial for anxiolytics, hypnotics and sedatives, and antidepressants. Prescription rates rose above those expected for all psychotropic medication classes except psychostimulants (RR, 1.12 [95% CI, 1.09-1.15] in adolescents and 1.06 [95% CI, 1.05-1.07] in children for antipsychotics; RR, 1.30 [95% CI, 1.25-1.35] in adolescents and 1.11 [95% CI, 1.09-1.12] in children for anxiolytics; RR, 2.50 [95% CI, 2.23-2.77] in adolescents and 1.40 [95% CI, 1.30-1.50] in children for hypnotics and sedatives; RR, 1.38 [95% CI, 1.29-1.47] in adolescents and 1.23 [95% CI, 1.20-1.25] in children for antidepressants; and RR, 0.97 [95% CI, 0.95-0.98] in adolescents and 1.02 [95% CI, 1.00-1.04] in children for psychostimulants). Changes were more pronounced among adolescents than children., Conclusions and Relevance: These findings suggest that prescribing of psychotropic medications for children and adolescents in France significantly and persistently increased after the COVID-19 pandemic onset. Future research should identify underlying determinants to improve psychological trajectories in young people.

Importance: Henoch-Schönlein purpura (HSP) is the most common type of vasculitis in children. The factors that trigger the disease are poorly understood. Although several viruses and seasonal bacterial infections have been associated with HSP, differentiating the specific associations of these pathogens with the onset of HSP remains a challenge due to their overlapping seasonal patterns., Objective: To analyze the role of seasonal pathogens in the epidemiology of HSP., Design, Setting, and Participants: This cohort study comprised an interrupted time-series analysis of patient records from a comprehensive national hospital-based surveillance system. Children younger than 18 years hospitalized for HSP in France between January 1, 2015, and March 31, 2023, were included., Exposure: Implementation and relaxation of nonpharmaceutical interventions (NPIs) for the COVID-19 pandemic, such as social distancing and mask wearing., Main Outcomes and Measures: The main outcomes were the monthly incidence of HSP per 100 000 children, analyzed via a quasi-Poisson regression model, and the estimated percentage of HSP incidence potentially associated with 14 selected common seasonal pathogens over the same period., Results: The study included 9790 children with HSP (median age, 5 years [IQR, 4-8 years]; 5538 boys [56.4%]) and 757 110 children with the infectious diseases included in the study (median age, 0.7 years [IQR, 0.2-2 years]; 393 697 boys [52.0%]). The incidence of HSP decreased significantly after implementation of NPIs in March 2020 (-53.6%; 95% CI, -66.6% to -40.6%; P < .001) and increased significantly after the relaxation of NPIs in April 2021 (37.2%; 95% CI, 28.0%-46.3%; P < .001). The percentage of HSP incidence potentially associated with Streptococcus pneumoniae was 37.3% (95% CI, 22.3%-52.3%; P < .001), the percentage of cases associated with Streptococcus pyogenes was 25.6% (95% CI, 16.7%-34.4%; P < .001), and the percentage of cases associated with human rhino enterovirus was 17.1% (95% CI, 3.8%-30.4%; P = .01). Three sensitivity analyses found similar results., Conclusions and Relevance: This study found that significant changes in the incidence of HSP simultaneously with major shifts in circulating pathogens after NPIs for the COVID-19 pandemic indicated that approximately 60% of HSP incidence was potentially associated with pneumococcus and group A streptococcus. This finding suggests that preventive measures against these pathogens could reduce the incidence of pediatric HSP.

Background: In France, vaccination has been implemented against Hi serotype b (Hib), pneumococcus with pneumococcal conjugate vaccines (PCV), and Neisseria meningitidis serogroup C (MenC). These interventions with different coverage and uptake have disrupted the epidemiology of vaccine-preventable acute bacterial meningitis (ABM)., Methods: We analyzed data from a French prospective surveillance network of ABM in children ≤15 years old enrolled by 259 pediatric wards (estimated national coverage: 61%). From 2001 to 2020, the effect of vaccine implementation was estimated with segmented linear regression., Results: We analyzed 7,186 cases, mainly due to meningococcus (35.0%), pneumococcus (29.8%), and Hi (3.7%). MenC ABM incidence decreased (-0.12%/month, 95% CI: -0.17 to -0.07, P < 0.001) with no change for the overall meningococcal ABM when comparing the pre-MenC vaccination and the post-MenC vaccination trends. Despite a decreasing MenB ABM incidence without a vaccination program (-0.43%/month, 95% CI: -0.53 to -0.34, P < 0.001), 68.3% of meningococcal ABM involved MenB. No change in pneumococcal ABM incidence was observed after the PCV7 recommendation. By contrast, this incidence significantly decreased after the switch to PCV13 (-0.9%/month, 95% CI: -1.6 to -0.2%, P = 0.01). After May 2014, a rebound occurred (0.5%/month, 95% CI: 0.3-0.8%, P < 0.001), with 89.5% of non-PCV13 vaccine serotypes. Hib ABM incidence increased after June 2017., Conclusions: PCV7 and MenC vaccine introduction in France, with slow vaccine uptake and low coverage, had no to little impact as compared to the switch from PCV7 to PCV13, which occurred when coverage was optimal. Our data suggest that MenB and next-generation PCVs could prevent a large part of the ABM incidence in France., Competing Interests: A.R. reports personal fees from MSD outside the submitted work and nonfinancial support from Pfizer and AstraZeneca. N.O. reported receiving grants from Pfizer to his institution during the conduct of the study and travel grants from Pfizer, Sanofi, and GlaxoSmithKline outside the submitted work. E.V. reports grants from a French public health agency, during the conduct of the study, grants from Pfizer and from MSD, outside the submitted work. M.K.T. performs contract work for the Institut Pasteur funded by GSK, Pfizer and Sanofi Pasteur. M.K.T. has a patent NZ630133A Patent with GSK “Vaccines for serogroup X meningococcus” issued. F.A. reports receiving personal fees from MSD, Sanofi, and AstraZeneca outside the submitted work. R.C. reported receiving personal fees from Sanofi, Pfizer, MSD, and GSK; travel grants from Pfizer and MSD, and grants from Sanofi, Pfizer, MSD, and GSK outside the submitted work. C.L. reported receiving grants from Pfizer during the conduct of the study, personal fees from Pfizer and MSD, and nonfinancial support from Pfizer outside the submitted work. The other authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs)., Research Question: What is the respective role of respiratory pathogens in ACS epidemiology?, Study Design and Methods: This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All children aged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen., Results: Among the 55,941 hospitalizations of children with SCD, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed in ACS incidence after NPI implementation in March 2020 (-29.5%; 95% CI, -46.8 to -12.2; P = .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95% CI, 7.2 to 41.6; P = .007). Using population-level incidence of several respiratory pathogens, Streptococcus pneumoniae accounted for 30.9% (95% CI, 4.9 to 56.9; P = .02) of ACS incidence over the study period and influenza 6.8% (95% CI, 2.3 to 11.3; P = .004); other respiratory pathogens had only a minor role., Interpretation: NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: N. O. reports travel grants from GlaxoSmithKline, Pfizer, and Sanofi. A. R. reports travel grants from Pfizer and AstraZeneca and personal fees from MSD outside the submitted work. A. V. reports personal fees from Sanofi, Moderna, GlaxoSmithKline, and MSD. R. C. reports speaking and lecture fees from Pfizer, Sanofi, GlaxoSmithKline, and MSD; and funding and travel grants from Pfizer. E. V. reports grants from Santé Publique France, Pfizer, and MSD. F. A. reports honoraria from Pfizer, GlaxoSmithKline, MSD, and Sanofi outside the submitted work. None declared (Z. A., Z. V., F. K., A. L., L.-L. P., L. L., A. F., M. C., C. L., F. G., B. K.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The value of formative objective structured clinical examinations (OSCEs) during the pre-clinical years of medical education remains unclear. We aimed to assess the effectiveness of a formative OSCE program for medical students in their pre-clinical years on subsequent performance in summative OSCE., Methods: We conducted a non-randomized controlled prospective pilot study that included all medical students from the last year of the pre-clinical cycle of the Université Paris-Cité Medical School, France, in 2021. The intervention group received the formative OSCE program, which consisted of four OSCE sessions, followed by debriefing and feedback, whereas the control group received the standard teaching program. The main objective of this formative OSCE program was to develop skills in taking a structured medical history and communication. All participants took a final summative OSCE. The primary endpoint was the summative OSCE mark in each group. A questionnaire was also administered to the intervention-group students to collect their feedback. A qualitative analysis, using a convenience sample, was conducted by gathering data pertaining to the process through on-site participative observation of the formative OSCE program., Results: Twenty students were included in the intervention group; 776 in the control group. We observed a significant improvement with each successive formative OSCE session in communication skills and in taking a structured medical history (p<0.0001 for both skills). Students from the intervention group performed better in a summative OSCE that assessed the structuring of a medical history (median mark 16/20, IQR [15; 17] versus 14/20, [13; 16], respectively, p = 0.012). Adjusted analyses gave similar results. The students from the intervention group reported a feeling of improved competence and a reduced level of stress at the time of the evaluation, supported by the qualitative data showing the benefits of the formative sessions., Conclusion: Our findings suggest that an early formative OSCE program is suitable for the pre-clinical years of medical education and is associated with improved student performance in domains targeted by the program., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ouldali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To examine whether the COVID-19 pandemic was associated with an increased incidence of uveitis in children., Study Design: We performed a time-series analysis of patient records from a national, hospital-based, French surveillance system. All children hospitalized for uveitis in France between January 2012 and March 2022 were included. The incidence of newly diagnosed uveitis per 100 000 children per trimester in France was analyzed by a quasi-Poisson regression. A cohort of children diagnosed with uveitis at Robert-Debré Hospital was used to compare the characteristics of uveitis after and before the onset of the pandemic., Results: During the study period, 2492 children were hospitalized for uveitis in France. The COVID-19 pandemic, which started in March 2020, was associated with a significant increase in the occurrence of uveitis (estimated cumulative change, 44.9%; 95% CI 11.4-78.4; P < .001). The increase in the incidence of pediatric uveitis started in October 2020, while the national immunization program targeting children aged less than 18 years began in June 2021. This increase involved all forms of uveitis, regardless of location, and clincial characteristics were similar to those diagnosed before the pandemic., Conclusions: Our study evidenced a significant increase in the incidence of pediatric uveitis following the COVID-19 pandemic. This increase occurred 6 months before the implementation of the national COVID-19 vaccination program for children, suggesting that the resurgence of this rare disease is independent of COVID-19 vaccination., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Haemophilus influenzae (Hi) is one of the leading bacteria implicated in childhood acute otitis media (AOM). Recent concerns have been raised about the emergence of Hi-resistant strains. We aimed to analyze the evolution of β-lactam resistance to Hi among strains isolated from nasopharyngeal carriage in children with AOM and in mild ear fluid (MEF) after the spontaneous perforation of the tympanic membrane (SPTM) in France. In this national ambulatory-based cohort study over 16 years, we analyzed the rate of Hi nasopharyngeal carriage and the proportion of β-lactam-resistant Hi strains over time using a segmented linear regression model. Among the 13,865 children (median [IQR] age, 12.7 [9.3-17.3] months; 7400 [53.4%] male) with AOM included from November 2006 to July 2022, Hi was isolated in 7311 (52.7%) children by nasopharyngeal sampling. The proportion of β-lactamase-producing and β-lactamase-negative, ampicillin-resistant (BLNAR) Hi strains in nasopharyngeal carriage remained stable during the study period. Among the 783 children (median [IQR] age, 20 [12.3-37.8] months; 409 [52.2%] male) with SPTM included from October 2015 to July 2022, Hi was isolated in 177 (22.6%) cases by MEF sampling. The proportions of β-lactamase-producing and BLNAR Hi strains did not significantly differ between nasopharyngeal (17.6% and 8.8%, respectively) and MEF (12.6% and 7.4%) samples. Accordingly, amoxicillin remains a valid recommendation as the first-line drug for AOM in France.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Knowledge of infectious diseases and their treatments is constantly evolving. New infectious agents are regularly discovered, mainly due 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, 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 only be prescribed by infectious diseases 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, for each clinical situation, the bacterial target(s) of antibiotic treatment, the preferred antibiotic choice, and the therapeutic alternatives will be specified. Comments on the diagnosis and treatment of the infection will be added if necessary., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Kawasaki disease is an acute, febrile, systemic vasculitis of children that primarily affects medium-sized blood vessels with a tropism for the coronary arteries. Although the etiological factors remain unknown, infections have been suggested as the trigger of Kawasaki disease. We sought to calculate the fraction of Kawasaki disease potentially attributable to seasonal infections., Methods: This cohort study used a population-based time series analysis from the French hospitalisation database (Programme de Médicalisation des Systèmes d'Information), which includes all inpatients admitted to any public or private hospital in France. We included all children aged 0-17 years hospitalised for Kawasaki disease in France over 13 years. The monthly incidence of Kawasaki disease per 10,000 children over time was analysed by a quasi-Poisson regression model. The model accounted for seasonality by using harmonic terms (a pair of sines and cosines with 12-month periods). The circulation of eight common seasonal pathogens (adenovirus, influenza, metapneumovirus, Mycoplasma pneumoniae , norovirus, rhinovirus, rotavirus, respiratory syncytial virus, and Streptococcus pneumonia ) over the same period was included in the model to analyse the fraction of Kawasaki disease potentially attributable to each pathogen. Infections were identified on the basis of polymerase chain reaction or rapid antigen testing in hospital laboratories., Findings: Between Jan 1, 2007, and Dec 31, 2019, we included 10,337 children with Kawasaki disease and 442,762 children with the selected infectious diseases. In the Kawasaki disease cohort, the median age [IQR] was 2 [0-4] years, 6164 [59.6%] were boys. Adenovirus infection was potentially responsible for 24.4% [21.5-27.8] (p < 0.001) of Kawasaki diseases, Norovirus for 6.7% [1.3-11.2] (p = 0.002), and RSV 4.6% [1.2-7.8] (p = 0.022). Sensitivity analyses found similar results., Interpretation: This cohort study of data from a comprehensive national hospitalisation database indicated that approximately 35% of Kawasaki diseases was potentially attributable to seasonal infections., Funding: None., Competing Interests: We declare no competing interests., (© 2023 The Authors.)

Context: Studies comparing initial therapy for multisystem inflammatory syndrome in children (MIS-C) provided conflicting results., Objective: To compare outcomes in MIS-C patients treated with intravenous immunoglobulin (IVIG), glucocorticoids, or the combination thereof., Data Sources: Medline, Embase, CENTRAL and WOS, from January 2020 to February 2022., Study Selection: Randomized or observational comparative studies including MIS-C patients <21 years., Data Extraction: Two reviewers independently selected studies and obtained individual participant data. The main outcome was cardiovascular dysfunction (CD), defined as left ventricular ejection fraction < 55% or vasopressor requirement ≥ day 2 of initial therapy, analyzed with a propensity score-matched analysis., Results: Of 2635 studies identified, 3 nonrandomized cohorts were included. The meta-analysis included 958 children. IVIG plus glucocorticoids group as compared with IVIG alone had improved CD (odds ratio [OR] 0.62 [0.42-0.91]). Glucocorticoids alone group as compared with IVIG alone did not have improved CD (OR 0.57 [0.31-1.05]). Glucocorticoids alone group as compared with IVIG plus glucocorticoids did not have improved CD (OR 0.67 [0.24-1.86]). Secondary analyses found better outcomes associated with IVIG plus glucocorticoids compared with glucocorticoids alone (fever ≥ day 2, need for secondary therapies) and better outcomes associated with glucocorticoids alone compared with IVIG alone (left ventricular ejection fraction < 55% ≥ day 2)., Limitations: Nonrandomized nature of included studies., Conclusions: In a meta-analysis of MIS-C patients, IVIG plus glucocorticoids was associated with improved CD compared with IVIG alone. Glucocorticoids alone was not associated with improved CD compared with IVIG alone or IVIG plus glucocorticoids.

Epidemiological surveillance of nasopharyngeal pneumococcal carriage is important for monitoring serotype distribution and antibiotic resistance, particularly before and after the implementation of pneumococcal conjugate vaccines (PCVs). With a prospective surveillance study in France, we aimed to analyze the dynamics of pneumococcal carriage, antibiotic susceptibility and serotype distribution in children aged 6 to 24 months who had acute otitis media between 2001 and 2022 with a focus on the late PCV13 period from May 2014 to July 2022. Trends were analyzed with segmented linear regression with autoregressive error. For the 17,136 children enrolled, overall pneumococcal carriage was stable during the study. During the late PCV13 period, the five most frequent serotypes were all non-PCV13 serotypes: 15B/C (14.3%), 23B (11.0%), 11A (9.6%), 15A (7.4%) and 35B (6.5%). During the same period, we observed a rebound of penicillin non-susceptibility (+0.15% per month, 95% confidence interval, +0.08 to 0.22, p < 0.001). Five serotypes accounted for 64.4% of the penicillin non-susceptible strains: 11A (17.5%), 35B (14.9%), 15A (13.9%), 15B/C (9.9%) and 19F (8.2%); non-PCV13/PCV15 accounted for <1%, and non-PCV15/PCV20 accounted for 28%. The next generation PCVs, particularly PCV20, may disrupt nasopharyngeal carriage and contribute to decreasing the rate of antibiotic resistance among pneumococci.

In a 15-year pediatric time-series analysis, we showed a rise of invasive Group A streptococcal (iGAS) infections since October 2022, mainly involving pleural empyema, simultaneously to a respiratory virus outbreak. Physicians should be aware of this increased risk of pediatric iGAS infections, especially in settings with intense respiratory viruses' circulation., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic autoimmune disease affecting multiple organs. Ranging from minor features, such as headache or mild cognitive impairment, to serious and life-threatening presentations, j-neuropsychiatric SLE (j-NPSLE) is a therapeutic challenge. Thus, the diagnosis of NPSLE remains difficult, especially in pediatrics, with no specific biomarker of the disease yet validated., Objectives: To identify central nervous system (CNS) disease biomarkers of j-NPSLE., Methods: A 5-year retrospective tertiary reference monocentric j-SLE study. A combination of standardized diagnostic criteria and multidisciplinary pediatric clinical expertise was combined to attribute NP involvement in the context of j-SLE. Neopterin and interferon-alpha (IFN-α) protein levels in cerebrospinal fluid (CSF) were assessed, together with routine biological and radiological investigations., Results: Among 51 patients with j-SLE included, 39% presented with j-NPSLE. J-NPSLE was diagnosed at onset of j-SLE in 65% of patients. No specific routine biological or radiological marker of j-NPSLE was identified. However, CSF neopterin levels were significantly higher in active j-NPSLE with CNS involvement than in j-SLE alone (p = 0.0008). Neopterin and IFN-α protein levels in CSF were significantly higher at diagnosis of j-NPSLE with CNS involvement than after resolution of NP features (respectively p = 0.0015 and p = 0.0010) upon immunosuppressive treatment in all patients tested (n = 10). Both biomarkers correlated strongly with each other (R s  = 0.832, p < 0.0001, n = 23 paired samples)., Conclusion: CSF IFN-α and neopterin constitute promising biomarkers useful in the diagnosis and monitoring of activity in j-NPSLE., (© 2022. The Author(s).)

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., Competing Interests: Conflict of interest: N. Ouldali reports travel grants from Pfizer, GSK and Sanofi. No other authors have conflicts of interest to disclose., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections., Methods: We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021-2022 was estimated., Findings: A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in <5-year-old children in October 2021, exceeding the pre-NPI trend (+62%). This was temporally associated with an unusual surge in RSV cases (+53% versus pre-NPI trend). During this 2021-22 surge, the fraction of IPD attributable to RSV dynamics in children was 77% (95% CI [33-100]). By contrast, the IPD incidence in older age-groups remained low, and was temporally associated with influenza dynamics., Interpretation: These results provide new evidence on the role of respiratory viruses in driving IPD dynamics, with possible differences between children and adults. In the coming future, the potential benefit of interventions targeting RSV, such as vaccines, for IPD prevention should be considered., Funding: The study was supported by a grant from the Quebec Ministry of Health and Social Services (' ministère de la Santé et des Services sociaux du Québec' ). Publication was supported by a grant from "Fondation de l'Assistance Publique - Hôpitaux de Paris et de l'Alliance « Tous Unis contre le Virus » (Fondation de France/Institut Pasteur/APHP)". N.O. was supported by the ESPID (European Society of Pediatric Infectious Diseases) 2021-2023 Fellowship Award and the 2022 ISPPD (International Symposium on Pneumococci and Pneumococcal Diseases) Robert Austrian Research award., Competing Interests: N.O. reports travel grants from Pfizer, Sanofi, and GSK, outside the present work. B.L. received research grants from Pfizer. All other authors report no potential conflicts., (© 2023 The Authors.)

Competing Interests: Competing interests: None declared.

Competing Interests: Conflicts of interest None disclosed.