OBJECTIVE:The COVID-19 pandemic may have affected the care of patients with influenza. We investigated influenza antiviral use and associated factors in children hospitalized with influenza before and during the late COVID-19 pandemic. METHODS:We conducted active surveillance among US children with acute respiratory illness at 7 sites in the New Vaccine Surveillance Network before the COVID-19 pandemic (December 1, 2016 to March 31, 2020) and during the late pandemic period (July 1, 2021 to June 30, 2023). We included children hospitalized within 10 days of symptom onset who had positive test results for influenza by clinical or research testing. Research swabs were collected from all enrolled children; clinical testing was provider-directed. We used mixed-effects Poisson regression to compare incidence proportions of influenza antiviral use in the late pandemic with those of the prepandemic period. We determined factors associated with antiviral use during the late pandemic period using a mixed-effects logistic regression model. RESULTS:Among 1560 children hospitalized with influenza, antiviral use ranged between 48.3% and 56.8% prepandemic but declined to 38.1% in 2021 to 2022 and 46.1% in 2022 to 2023. The estimated antiviral use was 23% lower in the late pandemic (incidence proportion ratio, 0.77; 95% CI, 0.68-0.87) compared with the prepandemic period. During the late pandemic, factors associated with higher odds of antiviral use included an underlying medical condition presence, current season influenza vaccination, clinical influenza testing, intensive care unit admission, and site. CONCLUSIONS:Influenza antiviral use in children hospitalized with influenza remained suboptimal following the COVID-19 pandemic. Our study highlights the need to improve antiviral use in children hospitalized with influenza.

INTRODUCTION:Infants are at risk of severe respiratory syncytial virus (RSV) infection. We characterized the humoral immune response of infants with primary RSV infection. METHODS:Term infants hospitalized for RSV-acute respiratory infection (ARI) or non-RSV-ARI (controls) were enrolled from November 2018 through March 2020 at 5 pediatric medical institutions. Adult controls were women aged 18-45 years without acute RSV infection. Acute and convalescent sera were tested for homologous and heterologous neutralizing antibodies (NtAbs), competitive antibodies (CA) to sites Ø, II, IV and I on the fusion (F) glycoprotein, and anti-postF and 27 amino acid peptide (p27) IgG. Geometric mean titer or CA concentration of acute and convalescent sera were compared between and within groups. RESULTS:Sixty-six infants (49 RSV infected and 17 controls) were enrolled. Median age was 76 (IQR 45-179) and 151 (IQR 72-207) days for RSV and control groups, respectively. NtAbs and CA at hospitalization were low among infant groups. Post-infection, RSV/A induced robust homologous and heterologous NtAb responses while RSV/B caused a robust NtAb response only to RSV/B. RSV/A infection generated significant CA rise to sites IV and II, while RSV/B infection resulted in only site II CA rise. Rises in postF and p27 IgG were not detected. Post-infection RSV antibody levels in infants were markedly lower compared to control adult women. CONCLUSION:RSV-infected infants had low pre-infection levels of protective antibodies. Infants infected with RSV/A compared to RSV/B generated a more robust NtAb response, highlighted by a broader CA response to sites II and IV.

Background: Pediatric CNS infections (CNSi)—meningitis, encephalitis, and craniospinal abscess—are uncommon, high-morbidity conditions in which timely emergency department (ED) diagnosis is critical and challenging. This study aimed to characterize the epidemiology of potential missed diagnosis (PMD) of CNSi and assess its association with acute neurological complications. Methods: Cross-sectional analysis of 2018 to 2019 Healthcare Cost and Utilization Project State ED and Inpatient datasets from California, Florida, Maryland, New York, and Wisconsin. Children aged 0 to 17 years with an admission for CNSi were included; those missing the linkage variable, birth hospitalizations, and with pre-existing intracranial devices were excluded. PMD was defined as a prior 7-day ED visit with a high-risk diagnosis, defined using Symptom-Disease Pair Analysis of Diagnostic Error methodology. Descriptive statistics and multivariable logistic regression were used to assess predictors of PMD and neurological complications. Results: Among 2686 CNSi cases, 284 (10.6%) had PMD with a median revisit interval of 2 days (IQR 1 to 3). In children >90 days with PMD, over 75% had isolated ED diagnoses of flu-like symptoms (fever, headache, vomiting, or fatigue), while 6% had CNSi “red flags” of altered mental status or neck pain. Potential missed diagnosis was more common in all age groups >90 days of age (aOR range: 4.19 to 4.78) and patients who were Asian (aOR 1.83, 95% CI: 1.06-3.16), Black (aOR 1.87, 95% CI: 1.30-2.70), and Hispanic (aOR 1.53, 95% CI: 1.1-2.13) relative to White children. In addition, patients initially presenting to lower annual pediatric volume quartile EDs (aOR 3.7, 95% CI: 2.6-5.3) and minor (aOR 1.49, 95% CI: 1.11-1.98) or nonteaching hospitals (aOR 2.08, 95% CI: 1.27-3.41) had higher risk of PMD. Among the subset of bacterial CNSi cases, PMD was associated with increased risk of neurological complications (aOR 2.49, 95% CI: 1.41-4.39). Conclusions: One in 10 children with CNSi had a potential missed diagnosis, most often after an initial ED visit for nonspecific flu-like symptoms. Risk of PMD was greater in children >90 days of age and those seen at lower-pediatric volume and nonacademic EDs. In addition, PMD in bacterial CNSi was associated with increased risk of severe neurological complications. These findings highlight the need for targeted diagnostic support tools to improve timely recognition of pediatric CNS infections, particularly in older infants and children.

The 2024-2025 influenza season was a high severity season for infants and children that resulted in the most pediatric deaths since the 2009 H1N1 pandemic. Maternal influenza vaccination during pregnancy is effective at preventing influenza illness in pregnant women and infants, has a strong safety record, and is recommended at any time during pregnancy. We assessed U.S. maternal influenza vaccine effectiveness (VE) against influenza illness among infants < 6 months, for whom there is no licensed influenza vaccine. We used a test-negative design to assess maternal influenza VE against laboratory-confirmed influenza illness among infants < 6 months with acute respiratory illness enrolled at seven pediatric medical institutions from 2016-2025. Influenza testing included molecular research and clinical testing results. Vaccination status was collected via state immunization information systems, providers, or self-report. VE was estimated by comparing the odds of maternal influenza vaccination ≥ 14 days prior to birth in case infants with influenza compared to control infants with non-influenza illness. VE was estimated overall, by medical setting, infant age, and timing of vaccination in pregnancy. We included 7236 infants; 414 cases and 6822 controls, of which 37% and 47% were born to mothers vaccinated during pregnancy, respectively (Table 1). VE was 34% (95% confidence interval, CI: 19-47%) overall and 42% (95% CI: 21%-57%) against hospitalization (Figure 1).VE was significant for infants born to mothers vaccinated ≥ 20 weeks gestation aged 0-2 (48%; 95% CI: 27%-63%) and 3-5 months (35%; 95% CI: 3%-57%) at encounter. VE was not significant for infants born to mothers vaccinated < 20 weeks gestation aged 0-2 and 3-5 months. Maternal influenza vaccination overall significantly reduced the odds of influenza illness among infants < 6 months of age, including in the high severity 2024-2025 season. Despite this, maternal influenza vaccination has recently declined, including in our study with less than half of infants born to mothers vaccinated during pregnancy. Efforts are needed to increase influenza vaccination uptake and better understand the optimal timing of influenza vaccination in pregnancy for both mom and baby. All Authors: No reported disclosures

BACKGROUND/OBJECTIVES:The Advisory Committee on Immunization Practices recommends the first dose of rotavirus vaccine (RVV) be delivered by a maximum age of 14 weeks, 6 days and that the vaccine not be delivered until time of discharge from the neonatal intensive care unit (NICU). We hypothesized that these guidelines limit the number of children who can be vaccinated with RVV. METHODS:Children born on or after January 1, 2007, enrolled in the New Vaccine Surveillance Network from December 2014 to August 2024 aged at least 15 weeks with rotavirus-negative acute gastroenteritis or as a healthy control, and with known vaccination status were included. We identified factors associated with not initiating or completing the RVV series and missed opportunities for vaccination. Odds ratios (ORs) and 95% CIs were calculated using univariate logistic regression. RESULTS:A total of 24 755 children met the inclusion criteria. The risk factors most strongly associated with not initiating RVV were receiving the diphtheria, tetanus, and pertussis vaccine at greater than or equal to age 15 weeks (OR, 30.0; 95% CI, 26.8-33.7), extremely preterm birth (OR, 14.6; 95% CI, 11.2-20.0), being born soon after RVV introduction (2007-2009) (OR, 3.3; 95% CI, 2.9-3.8), and having no health insurance (OR, 2.2; 95% CI, 1.8-2.7). More than 50% of extremely preterm infants in the NICU were not discharged until greater than or equal to age 15 weeks. CONCLUSIONS:Re-evaluation of the vaccine guidelines to allow RVV administration in the NICU may remove barriers to vaccination and help improve RVV coverage.

Abstract Background Human Adenovirus (HAdV) is frequently identified as a cause of acute respiratory infections (ARIs) in children and often co-detected with other common respiratory viruses. However, the effect of co-detection on disease severity is not well understood. This study aimed to describe the spectrum and frequency of other respiratory viruses co-detected with HAdV and define the impact of co-detection on HAdV disease severity. Methods Children admitted to the hospital or seen in the emergency department with fever and/or respiratory symptoms <14 days duration were enrolled at 7 sites across the US, from 12/01/2016 through 08/31/2023, as part of the CDC-sponsored New Vaccine Surveillance Network (NVSN). Respiratory specimens were systematically obtained and tested for HAdV and other common viral etiologies of ARI. Demographics, clinical characteristics, and disease severity (hospitalization and in-hospital oxygen use) were compared among children with HAdV single detection, HAdV co-detection with other respiratory viral pathogens, and single detection of a non-HAdV virus. Results Of 68,004 children enrolled with a respiratory specimen tested, 4,292 (6.3%) were positive for HAdV; 1,779 (41.4%) of these were HAdV single detections. Human rhinovirus/enterovirus (HRV/EV) (43.1%), respiratory syncytial virus (RSV) (14.7%), and parainfluenza virus (PIV) (7.6%) were the most common viruses co-detected with HAdV and selected for further analysis. HAdV co-detection with these 3 viruses was associated with increased odds of hospitalization and in-hospital oxygen use when compared to HAdV single detection. However, the odds of hospitalization and in-hospital oxygen use with HRV/EV, RSV, and PIV single detection were also increased compared to HAdV single detection. Conclusion HAdV co-detection with HRV/EV, RSV, or PIV was associated with increased disease severity when compared to HAdV single detection. However, HRV/EV, RSV, and PIV single detections were also associated with increased severity in comparison to HAdV single detection with these pathogens. Additionally, the increased odds of severe disease seen in HRV/EV, RSV, and PIV single detections was often greater than the increase seen with HAdV co-detection with HRV/EV, RSV, or PIV. This could suggest that the overall severity of these ARIs is being driven primarily by the co-detected viruses, HRV/EV, RSV, and PIV. These results could help guide interpretation of viral testing by clinicians, when multiple viruses are detected. Further research involving asymptomatic and mild HAdV ARI cases, as well as longitudinal studies to determine timing of co-infections, are needed to fully understand the role of HAdV in pediatric ARI of mixed viral etiology.

BACKGROUND:Risk factors for severe respiratory syncytial virus (RSV) illness include early infancy, premature birth, and underlying medical conditions. However, the clinical significance of respiratory viral co-detection is unclear. We compared the clinical outcomes of young children with RSV-only detection and those with RSV viral co-detection. METHODS:We conducted active, population-based surveillance of children with medically attended fever or respiratory symptoms at 7 US medical centers (1 December 2016-31 March 2020). Demographic and clinical data were collected through parental interviews and chart abstractions. Nasal swabs, with or without throat swabs, were systematically tested for RSV and 6 other common respiratory virus groups. We compared clinical outcomes, including hospitalization, and among those hospitalized, length of stay, intensive care unit admission, supplemental oxygen use, and intubation, between children aged <2 years with RSV-only detection and those with RSV co-detection. RESULTS:We enrolled 18 008 children aged <2 years. Of 17 841 (99.1%) tested for RSV, 5099 (28.6%) were positive. RSV was singly detected in 3927 children (77.0%) and co-detected in 1172 (23.0%). RSV co-detection with parainfluenza virus or adenovirus was associated with significantly lower odds of hospitalization (adjusted odds ratio, 0.56; 95% confidence interval [CI]: .33-.95; P = .031) and supplemental oxygen use (adjusted odds ratio, 0.66; 95% CI: .46-.95; P = .026), respectively, than RSV-only detection. For all other comparisons, we did not identify a significant association between RSV co-detection and worse clinical outcomes. CONCLUSIONS:Co-detection of RSV with another respiratory virus was not significantly associated with worse clinical outcomes compared with RSV-only detection.

Few studies compare long-term outcomes in children hospitalized for multisystem inflammatory syndrome in children (MIS-C) with children hospitalized for acute COVID-19. To inform clinical care and resource allocation, we compared patient characteristics and new post-hospitalization symptoms and diagnoses.Table 1.Clinical and demographic characteristics of children hospitalized for MIS-C or acute COVID-19 at time of hospitalizationTable 2.Number of children with new symptoms or diagnoses documented by ICD-10 code in the two years post-hospitalization for MIS-C or acute COVID-19 Children ≤18 years hospitalized April 2020-April 2022 for MIS-C or COVID-19 at 7 medical centers in the New Vaccine Surveillance Network (NVSN) were included. All children with MIS-C were identified from medical records; children with COVID-19 were limited to those previously enrolled in NVSN. Record abstraction and electronic data extraction were used to collect hospitalization data, and ICD-10 codes of interest within the hospital system in the 2 years before and after hospitalization. “New” symptoms and diagnoses were defined as those with ICD-10 codes not present pre-hospitalization and present post-hospitalization. We used Pearson’s chi-squared, Fisher's exact, and Wilcoxon rank sum tests to assess differences in characteristics and outcomes between MIS-C and COVID-19 patients. Among 736 children with MIS-C and 503 with COVID-19, children with MIS-C were older (median age 9.0 vs 4.1 years), lived in areas with lower median social vulnerability index scores (0.51 vs 0.60), and more often had no underlying medical conditions (76% vs 47%) (p< 0.001 for all; Table 1). Children with MIS-C more often required ICU admission (35% vs 15%; p< 0.001). After hospitalization, 55% in each group had ≥ 1 new diagnosis or symptom. Children with MIS-C more frequently had cardiac dysfunction (5% vs 1%) or other cardiovascular conditions (22% vs 7%) (p< 0.001 for each; Table 2). Children with COVID-19 more frequently had new diagnoses of asthma (13% vs 5%, p< 0.001), cardiorespiratory symptoms (23% vs 16%, p=0.002), gastrointestinal conditions (22% vs 17%, p=0.033), and sleep disturbances (8% vs 2%, p< 0.001; Table 2). Children hospitalized for MIS-C and COVID-19 differed by several characteristics including age, underlying conditions, and illness severity. After hospitalization, children with MIS-C more frequently had cardiac conditions; children with COVID-19 more frequently had respiratory, gastrointestinal, and sleep-related symptoms or diagnoses. Brian R. Lee, PhD, MPH, Merck: Grant/Research Support Elizabeth P. Schlaudecker, MD, MPH, Gilead: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Marian G. Michaels, MD, MPH, Merck: Grant/Research Support Danielle M. Zerr, MD MPH, AlloVir: Advisor/Consultant|Merck (Any division): Grant/Research Support Geoffrey A. Weinberg, MD, Inhalon Biopharma: Advisor/Consultant|Merck & Co: Honoraria Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|National Institutes of Health: Grant/Research Support|Up-To-Date: Royalties Rangaraj Selvarangan, PhD, Altona: Grant/Research Support|Biomerieux: Advisor/Consultant|Biomerieux: Grant/Research Support|Biomerieux: Honoraria|Cepheid: Grant/Research Support|Hologic: Grant/Research Support|Hologic: Honoraria|Meridian: Grant/Research Support|Qiagen: Grant/Research Support Natasha B. Halasa, MD, CSL-Seqirus: Advisor/Consultant|Merck: Grant/Research Support Janet A. Englund, MD, AstraZeneca: Board Member|AstraZeneca: Grant/Research Support|Cidarra: Member Data Safety Monitoring Board|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Tiphanie Vogel, MD, PhD, AstraZeneca: Grant/Research Support|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|SOBI: Advisor/Consultant|SOBI: Board Member|Takeda: Honoraria

Human adenovirus (HAdV) is a common cause of acute respiratory illness (ARI) in children and is frequently detected with other viruses (co-detection). The effect of co-detection on HAdV ARIs is incompletely understood, and recently the COVID-19 pandemic has disrupted the seasonality of many respiratory viruses. We aimed to characterize the demographics of children with HAdV ARI and co-detection patterns from 2016 through 2023.Table 1.Demographic characteristics of children with HAdV, stratified by detection status: single HAdV detection vs. HAdV co-detected with one or more respiratory virus(es), December 2016 to August 2023, New Vaccine Surveillance Network.1: The 2017 year includes cases from 12/01/2016 to 12/31/2017. The 2023 year includes cases from 01/01/2023 to 08/31/2023. We performed comparisons using Pearson’s χ2 test for categorical variables and the independent-samples t-test with unequal variances for continuous variables.Table 2.Single HAdV detection and HAdV co-detected with one or more respiratory virus(es), stratified by year, December 2016 to August 2023, New Vaccine Surveillance Network.Abbreviations: HAdV, human adenovirus; ccCoV, common cold coronaviruses; Flu, influenza; HMPV, human metapneumovirus; PIV, parainfluenza virus; HRV/RV, human rhinovirus/enterovirus; RSV, respiratory syncytial virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. 1Cells labeled NA indicate p-value could not be calculated due to zero cell counts. We performed comparisons using Pearson’s χ2 test for categorical variables and the independent-samples t-test with unequal variances for continuous variables. The New Vaccine Surveillance Network is an active, prospective, population-based ARI surveillance system at 7 US sites. Children < 18 years old with fever and/or ARI symptoms for < 14 days were enrolled if they were seen in the emergency department or admitted to the hospital. Nasal and/or oropharyngeal swabs were tested for respiratory viruses, and demographic information was collected. Demographics were compared between HAdV single detection and co-detections with other respiratory viruses, and the proportions of HAdV co-detections were compared between years.Figure 1.Seasonality of HAdV single detections and HAdV with other frequently co-detected viruses by percent of tested specimens, December 2016 to August 2023, New Vaccine Surveillance Network.Red line indicates when non pharmacologic interventions against SARS-CoV2 started in the US, March 2020 From Dec 2016 through Aug 2023, 4,292 of 66,662 (6.4%) children with ARI were positive for HAdV. 1,811 (42.2%) were single detections and 2,481 (57.8%) co-detections. Children with HAdV alone were older, had different racial/ethnic demographics, and were less likely to be privately insured, live with other children, or have an underlying respiratory condition (Table 1). The annual proportion of HAdV co-detections ranged from 43.5% to 66.8% (Table 2). The proportion of co-detections with specific viruses differed year to year for influenza, rhino/enterovirus, and respiratory syncytial virus, but not for common cold coronaviruses, human metapneumovirus, or parainfluenza virus. The variation and seasonality of HAdV-positivity and select co-detected virus fraction is shown in Figure 1. Most children with HAdV ARI had co-detection with another respiratory virus, with yearly variation in the proportion of co-detections and specific co-detected viruses. The demographics of children with HAdV single infection differed compared to those with co-detections, potentially representing varied exposure histories among different populations of children. These patterns could be relevant to HAdV ARI severity and inform management of HAdV infections. Rangaraj Selvarangan, PhD, Altona: Grant/Research Support|Biomerieux: Advisor/Consultant|Biomerieux: Grant/Research Support|Biomerieux: Honoraria|Cepheid: Grant/Research Support|Hologic: Grant/Research Support|Hologic: Honoraria|Meridian: Grant/Research Support|Qiagen: Grant/Research Support Marian G. Michaels, MD, MPH, Merck: Grant/Research Support Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|National Institutes of Health: Grant/Research Support|Up-To-Date: Royalties Elizabeth P. Schlaudecker, MD, MPH, Gilead: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Geoffrey A. Weinberg, MD, Inhalon Biopharma: Advisor/Consultant|Merck & Co: Honoraria Janet A. Englund, MD, AstraZeneca: Board Member|AstraZeneca: Grant/Research Support|Cidarra: Member Data Safety Monitoring Board|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support James Chappell, MD, PhD, Merck: Grant support for etiologic studies of acute respiratory illness in hospitalized children, Amman, Jordan Natasha B. Halasa, MD, CSL-Seqirus: Advisor/Consultant|Merck: Grant/Research Support

Background Procedural sedation is routinely provided for children in the emergency care setting. However, there are still significant gaps in knowledge regarding the optimal provision of sedation for children who are undergoing painful and/or distressing procedures. We aimed to develop a prioritised research agenda that identifies key questions for paediatric procedural sedation in the emergency care setting that will guide future research and optimise care for children.Methods We used a modified Delphi approach to achieve consensus among a multidisciplinary and geographically diverse expert advisory group. An initial list of 42 research questions was identified, with successive rounds of questionnaires conducted until there was a convergence of opinion or a point of diminishing returns was reached. The list was iteratively refined each round by advisory group members who ranked research questions and were given the opportunity to provide suggestions for potential additional questions and provide feedback regarding questions considered.Results 54 advisory group members participated in the modified Delphi approach. Over the course of two rounds, we identified 10 research questions as the highest priority for future investigation. These questions included topics addressing short- and long-term outcomes related to inadequate assessment and provision of sedation, patient-centered and family-centered outcomes, validity and reliability of clinically important outcome measures, most effective sedative regimens for children undergoing painful procedures, most effective sedative regimens for children undergoing non-painful procedures, most effective sedatives for minimal sedation/anxiolysis, effectiveness of novel sedation approaches, eliminating health disparities, clinician education and competency and the use of simulation to improve sedation outcomes.Conclusions The 10 research questions identified as highest priority can inform future work by researchers, funders, policymakers and other key decision makers who aim to meaningfully advance the provision of procedural sedation for children cared for in the emergency care setting.

During the 2023-2024 respiratory syncytial virus (RSV) season, two new RSV prevention products were recommended to protect US infants in their first RSV season, maternal RSV vaccine and nirsevimab. Using data from a 7-site respiratory virus surveillance network, we examined effectiveness of these products against medically attended RSV. Infants with outpatient, emergency department, and inpatient visits for acute respiratory illness were enrolled during the 2023-24 and 2024-25 RSV seasons. All children had molecular testing for RSV and clinical and demographic data collected from caregiver interviews, medical records, and immunization registries. A test-negative design was used to estimate maternal RSV vaccine effectiveness (VE) in children < 6 months in both seasons and nirsevimab effectiveness in infants in their first RSV season in 2024-25. Cases and controls were infants who tested positive and negative for RSV, respectively. Maternal RSV vaccination was receipt >14 days before infant birth. Nirsevimab receipt was administration >7 days before symptom onset. Among 1248 infants < 6 months without nirsevimab receipt, 27/344 (8%) case and 144/895 (16%) control patients had maternal RSV vaccination; median infant age was 44 days (IQR 23-84). Maternal RSV VE was 63% (95% CI 40-77%) against medically attended RSV and 74% (95% CI 54-86%) against RSV hospitalization. Among 1362 infants in their first RSV season without maternal RSV vaccination, 60/452 (13%) case and 372/910 (41%) control patients received nirsevimab. Nirsevimab effectiveness was 78% (95% CI 69-84%) against medically attended RSV (median interval from receipt=62 days, IQR 35-96) and 82% (95% CI 72-89%) against RSV hospitalization; effectiveness was similar by RSV type and prematurity status. Nirsevimab effectiveness varied by time since receipt from 92% (95% CI 80-97%) in infants < 30 days from receipt (median interval=21 days, IQR 15-24) to 69% (95% CI 48-82%) in infants 90-164 days from receipt (median interval=111 days, IQR 102-126). Under real-world conditions, both maternal RSV vaccine and nirsevimab effectively prevented medically attended RSV among infants in their first RSV season, with evidence of sustained nirsevimab protection through at least 5 months from receipt. All Authors: No reported disclosures

OBJECTIVES:Understanding the protection from influenza vaccines could help inform vaccine counseling, which might improve pediatric influenza vaccination uptake. We estimated vaccine effectiveness (VE) against influenza-associated hospitalization and outpatient visits during 3 influenza seasons (2021-2024). METHODS:We used data from 7 US pediatric medical centers within the New Vaccine Surveillance Network. We included children aged 6 months to 17 years who were hospitalized or received outpatient care for acute respiratory illness (ARI). We estimated VE against influenza-associated hospitalizations and outpatient visits with subgroup analyses for each season, stratifying by health care setting, age, and influenza virus type/subtype/genetic clade. RESULTS:Among 19 917 children with ARI, 2831 (14%) were positive and 17 086 (86%) were negative for influenza; 8523 (43%) were vaccinated, and 11 394 (57%) were unvaccinated. Vaccination uptake among children testing negative for influenza ranged from 44% to 51% by season. VE overall ranged from 34% to 60% across seasons, with the lowest VE estimates during 2021 to 2022. Effectiveness was 53% against influenza A/H1N1, 43% against A/H3N2, and 69% against B, with further variation by clade. CONCLUSIONS:From 2021 to 2024, pediatric influenza VE ranged from 34% to 60%, and overall was effective at preventing influenza-associated hospitalizations and outpatient visits. Effectiveness was higher against influenza B and lower during the 2021 to 2022 season. Vaccine uptake was low among children, with only half or fewer receiving the influenza vaccine each season. Influenza vaccination is the best way to reduce the risk of influenza for children. Improved pediatric influenza vaccination uptake would prevent additional influenza-associated hospitalizations and outpatient visits.

OBJECTIVE:Children with certain underlying conditions are at higher risk for severe influenza-related complications. In the United States, annual influenza vaccination is recommended for all children aged 6 months and older, yet vaccine effectiveness (VE) in children with underlying conditions remains less understood. We assessed VE against laboratory-confirmed influenza in children with and without underlying conditions presenting to emergency departments or admitted to hospitals. METHODS:We enrolled US children aged 6 months to 17 years at 7 pediatric medical centers within the New Vaccine Surveillance Network during 5 influenza seasons (2015-2020). Influenza status was confirmed by molecular testing and vaccination status was verified using state immunization registries or from health care clinicians. Underlying conditions were abstracted from medical records or self-reported by parents/guardians. VE was estimated by comparing the odds of vaccination among influenza-positive cases vs controls, adjusting for age, site, and calendar time. RESULTS:Of the 15 875 children included, 2821 (18%) tested positive for influenza. Overall, VE against influenza-associated emergency department visits or hospitalizations was 43% (95% CI: 35%-50%) for children with underlying conditions and 53% (95% CI: 47%-59%) for those without, and there was significant effect measure modification by the presence of underlying conditions (P = .04). VE was lowest among children with respiratory conditions (31%, 95% CI: 19%-42%). CONCLUSION:Influenza vaccination provided protection in both children with and children without underlying conditions. Efforts to improve influenza vaccination coverage and to initiate early treatment for influenza, particularly in populations at increased risk for severe influenza, are essential to reducing influenza-associated complications.

BACKGROUND:In 1999, the Centers for Disease Control and Prevention (CDC) established the New Vaccine Surveillance Network (NVSN) as a multi-site pediatric infectious diseases active surveillance system. METHODS:NVSN prospectively collects population-based clinical, epidemiologic, and laboratory information on children who seek medical care at hospitals, emergency departments, urgent care centers, and outpatient clinics with symptoms of acute respiratory infections (ARI) and acute gastroenteritis (AGE) in the United States. RESULTS:These efforts have clearly established the significant burden of both ARI and AGE in US children, demonstrated the effectiveness of licensed pediatric vaccines, and helped guide their use. The surveillance platform also measures the real-world impact of preventive measures intended to avoid or ameliorate adverse child health outcomes within the US healthcare system. Furthermore, NVSN provides a platform for detecting and evaluating emerging infections (e.g. enterovirus D-68, SARS-CoV-2) and unexpected sequelae in children. CONCLUSIONS:For 25 years NVSN has provided an evidence-based foundation for pediatric infectious disease policy decision-making through objective, empirical data. Sustained investment in disease surveillance guides the scientific principles and public health practices that prevent suffering and premature death, prepares us for new and existent pathogen threats, and enables wise economic decisions that improve the health of Americans.

BACKGROUND:Prematurity may place young children at increased risk for severe respiratory syncytial virus (RSV) disease because of differences in lung development. We describe characteristics of children aged less than 2 years hospitalized with RSV by prematurity and bronchopulmonary dysplasia (BPD) status and examine both as risk factors for severe in-hospital outcomes. METHODS:During 2016-2023, population-based surveillance was conducted at 7 medical centers for hospitalizations with RSV-associated acute respiratory illness in children. Poisson regression with robust variance was used to estimate adjusted relative risks (aRRs) of prolonged hospitalization (≥3 days), intensive care unit (ICU) admission, and assisted ventilation by age in children with prematurity without and with BPD compared with term children after adjustment for surveillance site and palivizumab receipt. RESULTS:Among 5844 children, 4626 (79.2%) were term and 1218 (20.8%) were premature, including 1138 (93.4%) without BPD and 80 (6.6%) with BPD. Compared with term children, all premature children had greater risks for prolonged hospitalization (aRR = 1.3; 95% CI, 1.2-1.5), ICU admission (aRR = 1.4; 95% CI, 1.2-1.6), and assisted ventilation (aRR = 2.0; 95% CI, 1.4-2.8) at chronological age less than 6 months. Premature children with BPD also had greater risk for prolonged hospitalization at all ages through 23 months. CONCLUSIONS:Premature children accounted for 1 in 5 hospitalizations among children aged less than 2 years hospitalized with RSV. Compared with term children, all premature children had increased risk for severe in-hospital outcomes in early infancy, and those with BPD remained at increased risk of prolonged hospitalization through age 23 months.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among US infants. The 2024-2025 season was the first full season with widely available RSV prevention products, (nirsevimab and maternal RSV vaccination) recommended for all infants aged < 8 months. To assess the impact of these products on RSV-associated hospitalizations, we compared RSV-associated hospitalization rates in infants aged < 6 months from 2017-2020 to 2024-2025.Table 1.Incidence rates of RSV-associated hospitalizations per 1,000 infants by site among infants <6 months of age, New Vaccine Surveillance Network, October-March 2017-2020 and 2024-2025 (N=1,299)Figure 1.Incidence rates of RSV-associated hospitalizations per 1,000 infants by site among infants <6 months of age, New Vaccine Surveillance Network, October-March 2017-2020 and 2024-2025 (N=1,299) Infants < 6 months of age hospitalized with acute respiratory illness (ARI) were systematically enrolled at 7 US medical centers. Nasal swabs were tested for RSV by reverse transcription polymerase chain reaction. RSV circulation was determined by the percent of RSV positives among all enrolled children from September-March 2024-2025. RSV-associated hospitalizations per 1,000 infants were calculated by site during October-March 2017-2020 and 2024-2025 using US census population denominators. 95% confidence intervals (CI) were estimated by bootstrap percentiles based on 1,000 bootstrap samples. Rates were adjusted for enrollment rates, surveillance days per week, test sensitivity, and hospital market share. The relative rate reduction (RRR) was calculated as (1 – rate ratio)*100%.Figure 2.Respiratory syncytial virus (RSV) circulation by site, New Vaccine Surveillance Network, September-March 2024-2025 Among 1,299 infants aged < 6 months, RSV-associated hospitalization rates decreased from 18.5 (95% CI 17.6 - 19.4) in 2017-2020 to 11.5 (95% CI 10.0 - 13.2) in 2024-2025, a 38% reduction (RR 0.62, 95% CI 0.54 - 0.72). The magnitude of reduction varied by site, ranging from 16% in Houston, TX (RR 0.84, 95% CI 0.70 - 1.01) to 75% in Rochester, NY (RR 0.25, 95% CI 0.13 - 0.37). Kansas City, MO (RR 0.34 95% CI 0.22 - 0.48), Pittsburgh, PA (RR 0.44, 95% CI 0.30 - 0.58), and Cincinnati, OH (RR 0.46, 95% CI 0.27 - 0.68) also had greater than 50% reductions. RSV circulation varied, beginning in September in Houston, TX and October/November in all other sites. RSV-associated hospitalizations decreased 38% among infants < 6 months of age, with reductions varying by location. The magnitude of impact was reduced in sites with earlier RSV season onset, highlighting the importance of timing local product uptake relative to the RSV season in optimizing reduction of RSV-associated hospitalizations across the US. All Authors: No reported disclosures

Human astroviruses are a common cause of viral gastroenteritis and are often underdiagnosed. While infections are typically mild or asymptomatic in immunocompetent hosts, astrovirus can cause prolonged and severe disease in immunocompromised individuals. Here, we conducted a case-control study to evaluate the clinical presentation of astrovirus infections in paediatric oncology patients. Our findings were compared to two groups: (1) norovirus infections in the same immunocompromised cohort, and (2) a cohort of immunocompetent children with and without diarrheal symptoms. Astrovirus was detected in 9.8% of immunocompromised patients, with prolonged shedding seen in multiple cases. Astrovirus infection was associated with an increased odds of diarrhoea, although this association weakened when adjusting for co-infections. In contrast, norovirus was not significantly associated with diarrhoea in immunocompromised patients, despite prolonged shedding in 24% of the cohort. High rates of co-infection with adenovirus and Clostridium difficile may have influenced symptom patterns. In the immunocompetent cohort, astrovirus was not associated with diarrhoea, while norovirus showed a strong association with symptoms. These findings indicate that astrovirus infections are more likely to cause diarrhoea in immunocompromised paediatric patients, while often asymptomatic in immunocompetent children. Norovirus showed the opposite trend, highlighting distinct roles of host immune status in shaping clinical outcomes. These findings highlight the importance of considering astrovirus as a potential contributor to gastrointestinal symptoms in immunocompromised children and call for broader diagnostic testing and further research on viral co-infections and persistence.

Children undergoing hematopoietic stem cell transplantation (HSCT) are at elevated risk for severe acute respiratory infections (ARI). We compared clinical outcomes between HSCT recipients and immunocompetent children with medically attended ARI using CDC’s New Vaccine Surveillance Network data. Comparison of Hematopoietic Stem Cell Transplant (HSCT) Recipients vs. Immunocompetent Children with Medically Attended Acute Respiratory Illness, New Vaccine Surveillance Network (NVSN), Dec 2016 – Sep 2020 Abbreviations: IQR = Interquartile range, LOS = Length of Stay Comparisons were made using Chi-squared tests for categorical variables and Wilcoxon rank-sum tests for continuous age and length of stay Viruses Identified Among HSCT Pediatric Cases, December 2016- September 2020 This prospective, multicenter study enrolled children < 18 years with ARI across seven U.S. health systems (2016–2020). Children were enrolled if seen in the ED or hospitalized. Respiratory specimens were tested by RT-PCR for common viruses on mid-turbinate nasal swabs. Exclusion criteria included illness >14 days, non-respiratory diagnoses, recent prior hospitalization, neonates never discharged home, and neutropenic fever (ANC < 500). Children were immunocompetent if they lacked HSCT, transplant, malignancy, sickle cell disease, or other immunosuppression. Comparisons used Chi-squared and Wilcoxon rank-sum tests. Viruses Identified Among Immunocompetent Pediatric Cases, December 2016- September 2020 A total of 60 HSCT and 35,037 immunocompetent children were enrolled. Median age was higher in HSCT recipients (9.5 vs. 1.9 years; p< 0.01). HSCT patients were more often hospitalized (91.7% vs. 49.0%; p < 0.01). Among 55 HSCT and 17,158 immunocompetent hospitalized patients, ICU admission (14.6% vs. 17.3%; p=0.86) and intubation (1.6% vs. 3.4%; p=0.80) rates were similar. However, mortality was higher in HSCT (1.7% vs. 0.1%; p< 0.01). Median LOS was longer in HSCT (3 vs. 2 days), with fewer discharged in 0–1 day (30.9% vs. 45.3%) and more hospitalized ≥ 5 days (25.5% vs. 13.1%; p< 0.01). Among influenza-positive patients, oseltamivir use was higher in HSCT (90.9% vs. 34.3%; p< 0.01). HSCT recipients with ARI were older, more frequently hospitalized, stayed longer, and had higher mortality, underscoring the need for enhanced preventive strategies in this population. All Authors: No reported disclosures

BACKGROUND:Comprehensive data are needed to guide the use and interpretation of molecular respiratory viral testing in evaluating infants 0 to ≤90 days old for invasive bacterial infections (IBIs). We aimed to describe the frequency and severity of respiratory viral infections in febrile and nonfebrile infants 0 to ≤90 days of age with emergency department visits or hospitalizations for acute respiratory illness and to quantify the occurrence of IBI (bacteremia and bacterial meningitis) in these groups. METHODS:The New Vaccine Surveillance Network conducts acute respiratory illness surveillance at 7 US pediatric medical institutions in the United States. We conducted a cross-sectional analysis of febrile and nonfebrile infants 0 to ≤90 days of age enrolled in the emergency department or inpatient hospital settings. Respiratory viral detection from research respiratory samples in the context of clinical severity and IBI was examined. RESULTS:Three thousand seven hundred and eighty febrile and nonfebrile infants 0 to ≤90 days of age enrolled from December 1, 2016, to March 31, 2020. Respiratory syncytial virus was the most common virus detected regardless of febrile status. IBIs were significantly more frequent in febrile infants without a respiratory virus compared with those with a respiratory virus detected (4.9% vs. 1.3%; P < 0.001). IBIs were not detected in infants with respiratory syncytial virus (n = 259), parainfluenza virus (n = 66), human metapneumovirus (n = 13), influenza virus (n = 67), or adenovirus (n = 11) alone. IBI and respiratory viral coinfections were found in infants with endemic coronaviruses (5.8%, 3/52), rhinovirus/enterovirus (2.2%, 7/324) and viral coinfections (2.0%, 2/99). CONCLUSIONS:These data suggest that febrile infants 0 to ≤90 days old with certain respiratory viruses are at lower risk of IBI.