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Studies have shown egg-adaptive mutations in influenza vaccine strains that might have impaired protection against circulating A(H3N2) influenza viruses during the 2016–2017 and 2017–2018 seasons. We used the test-negative design and multivariable models to assess vaccine effectiveness against influenza-associated hospitalization and emergency department visits among children (<18 years old) during the 2016–2017 and 2017–2018 seasons. Effectiveness was 71% (95% confidence interval, 59%–79%), 46% (35%–55%), and 45% (33%–55%) against A(H1N1)pdm09, A(H3N2), and B viruses respectively, across both seasons. During high-severity seasons with concerns for vaccine mismatch, vaccination offered substantial protection against severe influenza outcomes requiring hospitalization or emergency department visits among children. [ABSTRACT FROM AUTHOR]

Background: Antiviral treatment is recommended for all hospitalized children with suspected or confirmed influenza, regardless of their risk profile. Few data exist on adherence to these recommendations, so we sought to determine factors associated with influenza testing and antiviral treatment in children. Methods: Hospitalized children <18 years of age with acute respiratory illness (ARI) were enrolled through active surveillance at pediatric medical centers in seven cities between 11/1/2015 and 6/30/2016; clinical information was obtained from parent interview and chart review. We used generalized linear mixed‐effects models to identify factors associated with influenza testing and antiviral treatment. Results: Of the 2299 hospitalized children with ARI enrolled during one influenza season, 51% (n = 1183) were tested clinically for influenza. Clinicians provided antiviral treatment for 61 of 117 (52%) patients with a positive influenza test versus 66 of 1066 (6%) with a negative or unknown test result. In multivariable analyses, factors associated with testing included neuromuscular disease (aOR = 5.35, 95% CI [3.58–8.01]), immunocompromised status (aOR = 2.88, 95% CI [1.66–5.01]), age (aOR = 0.93, 95% CI [0.91–0.96]), private only versus public only insurance (aOR = 0.78, 95% CI [0.63–0.98]), and chronic lung disease (aOR = 0.64, 95% CI [0.51–0.81]). Factors associated with antiviral treatment included neuromuscular disease (aOR = 1.86, 95% CI [1.04, 3.31]), immunocompromised state (aOR = 2.63, 95% CI [1.38, 4.99]), duration of illness (aOR = 0.92, 95% CI [0.84, 0.99]), and chronic lung disease (aOR = 0.60, 95% CI [0.38, 0.95]). Conclusion: Approximately half of children hospitalized with influenza during the 2015–2016 influenza season were treated with antivirals. Because antiviral treatment for influenza is associated with better health outcomes, further studies of subsequent seasons would help evaluate current use of antivirals among children and better understand barriers for treatment. [ABSTRACT FROM AUTHOR]

At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections (ARIs) in hospitalized children. Although prematurity and underlying medical conditions are known risk factors, most of these children are healthy, and factors including RSV load and subgroups may contribute to severity. Therefore, we aimed to evaluate the role of RSV in ARI severity and determine factors associated with increased RSV-ARI severity in young children. Methods Children aged <5 years with fever and/or ARI symptoms were recruited from the emergency department (ED) or inpatient settings at Vanderbilt Children's Hospital. Nasal and/or throat swabs were tested using quantitative reverse-transcription polymerase chain reaction for common respiratory viruses, including RSV. A severity score was calculated for RSV-positive children. Results From November 2015 through July 2016, 898 participants were enrolled, and 681 (76%) had at least 1 virus detected, with 191 (28%) testing positive for RSV. RSV-positive children were more likely to be hospitalized, require intensive care unit admission, and receive oxygen compared with children positive for other viruses. Higher viral load, White race, younger age, and higher severity score were independently associated with hospitalization in RSV-positive children. No differences in disease severity were noted between RSV A and RSV B. Conclusions RSV was associated with increased ARI severity in young children enrolled from the ED and inpatient settings, but no differences in disease severity were noted between RSV A and RSV B. These findings emphasize the need for antiviral therapy and/or preventive measures such as vaccines against RSV in young children. [ABSTRACT FROM AUTHOR]

Background. Norovirus is a leading cause of epidemic acute gastroenteritis (AGE), with most outbreaks occurring during winter. The majority of outbreaks are caused by GII.4 noroviruses; however, data to support whether this is true for sporadic medically attended AGE are limited. Therefore, we sought to compare the clinical characteristics and seasonality of GII.4 vs non-GII.4 viruses. Methods. Children aged 15 days -17 years with AGE symptoms were recruited from the outpatient, emergency department, and inpatient settings at Vanderbilt Children’s Hospital, Davidson County, Nashville, Tennessee, from December 2012 -November 2015. Stool specimens were tested using qRT-PCR for GI and GII noroviruses and subsequently genotyped by sequencing a partial region of the capsid gene. Results. A total of 3705 patients were enrolled, and stool specimens were collected and tested from 2885 (78%) enrollees. Overall, 636 (22%) samples were norovirus-positive, of which 567 (89%) were GII. Of the 460 (81%) genotyped GII-positive samples, 233 (51%) were typed as GII.4 and 227 (49%) as non-GII.4. Compared with children with non-GII.4 infections, children with GII.4 infections were younger, more likely to have diarrhea, and more likely to receive oral rehydration fluids. Norovirus was detected year-round and peaked during winter. Conclusions. Approximately 40% of sporadic pediatric norovirus AGE cases were caused by GII.4 norovirus. Children infected with GII.4 had more severe symptoms that required more medical care. Seasonal variations were noticed among different genotypes. These data highlight the importance of continuous norovirus surveillance and provide important information on which strains pediatric norovirus vaccines should protect against. [ABSTRACT FROM AUTHOR]

Background The 2019–2020 influenza season was characterized by early onset with B/Victoria followed by A(H1N1)pdm09 viruses. Emergence of new B/Victoria viruses raised concerns about possible vaccine mismatch. We estimated vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department (ED) visits among children in the United States. Methods We assessed VE among children aged 6 months–17 years with acute respiratory illness and ≤10 days of symptoms enrolled at 7 pediatric medical centers in the New Vaccine Surveillance Network. Combined midturbinate/throat swabs were tested for influenza virus using molecular assays. Vaccination history was collected from parental report, state immunization information systems, and/or provider records. We estimated VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive vs negative for influenza. Results Among 2029 inpatients, 335 (17%) were influenza positive: 37% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval [CI], 52%–71%) for influenza-related hospitalizations, 54% (95% CI, 33%–69%) for B/Victoria viruses, and 64% (95% CI, 49%–75%) for A(H1N1)pdm09. Among 2102 ED patients, 671 (32%) were influenza positive: 47% with influenza B/Victoria alone and 42% with influenza A(H1N1)pdm09 alone. VE was 56% (95% CI, 46%–65%) for an influenza-related ED visit, 55% (95% CI, 40%–66%) for B/Victoria viruses, and 53% (95% CI, 37%–65%) for A(H1N1)pdm09. Conclusions Influenza vaccination provided significant protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the 2 predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus subclade. [ABSTRACT FROM AUTHOR]

Background Parent-reported influenza vaccination history may be valuable clinically and in influenza vaccine effectiveness (VE) studies. Few studies have assessed the validity of parental report among hospitalized children. Methods Parents of 2597 hospitalized children 6 months–17 years old were interviewed from November 1, 2015 to June 30, 2016, regarding their child's sociodemographic and influenza vaccination history. Parent-reported 2015–2016 influenza vaccination history was compared with documented vaccination records (considered the gold standard for analysis) obtained from medical records, immunization information systems, and providers. Multivariable logistic regression analyses were conducted to determine potential factors associated with discordance between the 2 sources of vaccination history. Using a test-negative design, we estimated VE using vaccination history obtained through parental report and documented records. Results According to parental report, 1718 (66%) children received the 2015–2016 influenza vaccine, and of those, 1432 (83%) had documentation of vaccine receipt. Percent agreement was 87%, with a sensitivity of 96% (95% confidence interval [CI], 95%–97%) and a specificity of 74% (95% CI, 72%–77%). In the multivariable logistic regression, study site and child's age 5–8 years were significant predictors of discordance. Adjusted VE among children who received ≥1 dose of the 2015–2016 influenza vaccine per parental report was 61% (95% CI, 43%–74%), whereas VE using documented records was 55% (95% CI, 33%–69%). Conclusions Parental report of influenza vaccination was sensitive but not as specific compared with documented records. However, VE against influenza-associated hospitalizations using either source of vaccination history did not differ substantially. Parental report is valuable for timely influenza VE studies. [ABSTRACT FROM AUTHOR]

Background Acute gastroenteritis (AGE) is a common reason for children to receive medical care. However, the viral etiology of AGE illness is not well described in the post–rotavirus vaccine era, particularly in the outpatient (OP) setting. Methods Between 2012 and 2015, children 15 days through 17 years old presenting to Vanderbilt Children's Hospital, Nashville, Tennessee, with AGE were enrolled prospectively from the inpatient, emergency department, and OP settings, and stool specimens were collected. Healthy controls (HCs) were enrolled and frequency matched for period, age group, race, and ethnicity. Stool specimens were tested by means of reverse-transcription real-time quantitative polymerase chain reaction for norovirus, sapovirus, and astrovirus RNA and by Rotaclone enzyme immunoassay for rotavirus antigen, followed by polymerase chain reaction verification of antigen detection. Results A total of 3705 AGE case patients and 1563 HCs were enrolled, among whom 2885 case patients (78%) and 1110 HCs (71%) provided stool specimens that were tested. All 4 viruses were more frequently detected in AGE case patients than in HCs (norovirus, 22% vs 8%, respectively; rotavirus, 10% vs 1%; sapovirus, 10% vs 5%; and astrovirus, 5% vs 2%; P  < .001 for each virus). In the OP setting, rates of AGE due to norovirus were higher than rate for the other 3 viruses. Children <5 years old had higher OP AGE rates than older children for all viruses. Conclusions Norovirus remains the most common virus detected in all settings, occurring nearly twice as frequently as the next most common pathogens, sapovirus and rotavirus. Combined, norovirus, sapovirus, rotavirus, and astrovirus were associated with almost half of all AGE visits and therefore are an important reason for children to receive medical care. [ABSTRACT FROM AUTHOR]

Background In the United States, surveillance of norovirus gastroenteritis is largely restricted to outbreaks, limiting our knowledge of the contribution of sporadic illness to the overall impact on reported outbreaks. Understanding norovirus transmission dynamics is vital for improving preventive measures, including norovirus vaccine development. Methods We analyzed seasonal patterns and genotypic distribution between sporadic pediatric norovirus cases and reported norovirus outbreaks in middle Tennessee. Sporadic cases were ascertained via the New Vaccine Surveillance Network in a single county, while reported norovirus outbreaks from 7 middle Tennessee counties were included in the study. We investigated the predictive value of sporadic cases on outbreaks using a 2-state discrete Markov model. Results Between December 2012 and June 2016, there were 755 pediatric sporadic norovirus cases and 45 reported outbreaks. Almost half (42.2%) of outbreaks occurred in long-term care facilities. Most sporadic cases (74.9%) and reported outbreaks (86.8%) occurred between November and April. Peak sporadic norovirus activity was often contemporaneous with outbreak occurrence. Among both sporadic cases and outbreaks, GII genogroup noroviruses were most prevalent (90.1% and 83.3%), with GII.4 being the dominant genotype (39.0% and 52.8%). The predictive model suggested that the 3-day moving average of sporadic cases was positively associated with the probability of an outbreak occurring. Conclusions Despite the demographic differences between the surveillance populations, the seasonal and genotypic associations between sporadic cases and outbreaks are suggestive of contemporaneous community transmission. Public health agencies may use this knowledge to expand surveillance and identify target populations for interventions, including future vaccines. [ABSTRACT FROM AUTHOR]

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection. Both influenza vaccination and early initiation of antiviral treatment can reduce complications of influenza. Using data from two U.S. influenza surveillance networks for children and adolescents aged <18 years with medically attended, laboratory-confirmed influenza for whom antiviral treatment is recommended, the percentage who received treatment was calculated. Trends in antiviral treatment of children and adolescents hospitalized with influenza from the 2017-18 to the 2023-2024 influenza seasons were also examined. Since 2017-18, when 70%-86% of hospitalized children and adolescents with influenza received antiviral treatment, the proportion receiving treatment notably declined. Among children and adolescents with influenza during the 2023-24 season, 52%-59% of those hospitalized received antiviral treatment. During the 2023-24 season, 31% of those at higher risk for influenza complications seen in the outpatient setting in one network were prescribed antiviral treatment. These findings demonstrate that influenza antiviral treatment is underutilized among children and adolescents who could benefit from treatment. All hospitalized children and adolescents, and those at higher risk for influenza complications in the outpatient setting, should receive antiviral treatment as soon as possible for suspected or confirmed influenza., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Janet A. Englund reports institutional support from AstraZeneca, Pfizer, Moderna, and GlaxoSmithKline; receipt of consulting fees from AstraZeneca, GlaxoSmithKline, Merck, Meissa Vaccines, Moderna, Pfizer, and Sanofi Pasteur; and receipt of honoraria from Pfizer. Natasha B. Halasa reports institutional support from Merck, and receipt of an honorarium from CSL Seqirus for service on an advisory board. Sue Kim reports grants from the Michigan Department of Health and Human Services. Ruth Lynfield reports receipt of a fee for serving as an Associate Editor for the American Academy of Pediatrics Redbook, which was then donated to the Minnesota Department of Health. Leila C. Sahni reports travel support from the Gates Foundation. Elizabeth P. Schlaudecker reports institutional support from Pfizer; receipt of an honorarium from Sanofi Pasteur for service on an advisory board; and travel support for meeting attendance from the World Society for Pediatric Infectious Diseases, the European Society for Paediatric Infectious Diseases, and Pediatric Infectious Diseases Society; uncompensated membership of a National Institutes of Health Data Safety Monitoring Board; and membership on the board of the World Society for Pediatric Infectious Diseases. Jennifer E. Schuster reports institutional support from the National Institutes of Health, the Food and Drug Administration and the State of Missouri; receipt of a consulting fee from the Association of Professionals in Infection Control and Epidemiology and a speaking honorarium from the Missouri Chapter of the American Academy of Pediatrics; membership on the Association of American medical Colleges advisory board. Rangaraj Selvarangan reports institutional support from Abbot, Cepheid, Biomerieux, Hologic, BioRad, Qiagen, Diasorin, and Merck; receipt of payment from GlaxoSmithKline, Baebies Biomerieux and Abbot; and travel support from Biomerieux and Hologic. Mary A. Staat reports institutional support from the National Institutes of Health, Cepheid, and Merck; royalties from UpToDate; and consulting fees from Merck. Dawud Ujamaa reports consulting fees from Goldbelt, Inc. Geoffrey A. Weinberg reports institutional support from the New York State Department of Health; consulting fees from the New York State Department of Health, Inhalon Biopharma, and ReViral; honorarium from Merck; and participation on an Emory University Data Safety Monitoring Board. No other potential conflicts of interest were disclosed.

Background: Previous investigations into clinical signs and symptoms associated with influenza types and subtypes have not definitively established differences in the clinical presentation or severity of influenza disease., Methods: The study population included children 0 through 17 years old enrolled at 8 New Vaccine Surveillance Network sites between 2015 and 2020 who tested positive for influenza virus by molecular testing. Demographic and clinical data were collected for study participants via parent/guardian interview and medical chart review. Descriptive statistics were used to summarize demographic and clinical characteristics by influenza subtype. Multivariable logistic regression and Cox proportional hazard models were used to assess effects of age, sex, influenza subtype, and history of asthma on severity, including hospital admission, need for supplemental oxygen, and length of stay., Results: Retractions, cyanosis, and need for supplemental oxygen were more frequently observed among patients with influenza A(H1N1)pdm09. Headaches and sore throat were more commonly reported among patients with influenza B. Children with influenza A(H1N1)pdm09 and children with asthma had significantly increased odds of hospital admission (adjusted odds ratio (AOR): 1.39, 95% CI: 1.14-1.69 and AOR: 2.14, 95% CI: 1.72-2.67, respectively). During admission, children with influenza A(H1N1)pdm09 had significantly increased use of supplemental oxygen compared to children with A(H3N2) (AOR: 0.60, 95% CI: 0.44-0.82) or B (AOR: 0.56, 95% CI: 0.41-0.76)., Conclusions: Among children presenting to the emergency department and admitted to the hospital, influenza A(H1N1)pdm09 caused more severe disease compared to influenza A(H3N2) and influenza B. Asthma also contributed to severe influenza disease regardless of subtype., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Pediatric hematopoietic cell transplant (HCT) recipients are at high-risk for morbidity from influenza virus infection. We demonstrated in a primary phase II randomized controlled trial that two post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given four weeks apart were more immunogenic than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen., Methods: A subcohort of study participants re-enrolled and had hemagglutinin inhibition (HAI) titers measured at baseline and four weeks after each vaccine dose in year two. We estimated geometric mean fold rise (GMFR) in HAI titer from baseline for each group and used linear mixed effects models to estimate adjusted geometric mean ratios (aGMR, comparing HD-TIV to SD-QIV) for each antigen at each time point. We described systemic and injection-site reactions., Results: A total of 65 subcohort patients participated (33 SD-QIV, 32 HD-TIV). Post-vaccine GMFR and aGMR estimates were higher for both groups following a single influenza vaccine dose in year two compared to two doses of the same formulation in year one. Both groups had similar frequencies of injection-site and systemic reactions., Conclusions: A single dose of HD-TIV or SD-QIV was more immunogenic in year two than two doses of the same formulation in year one. Reactogenicity was comparable between groups. One dose of influenza vaccine may be sufficient after a two-dose schedule in the prior year post-HCT., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants aged <8 months to protect against RSV-associated lower respiratory tract infection during their first RSV season and for children aged 8-19 months at increased risk for severe RSV disease. In phase 3 clinical trials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%-90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023-February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, 59 (8%) received nirsevimab ≥7 days before symptom onset. Nirsevimab effectiveness was 90% (95% CI = 75%-96%) against RSV-associated hospitalization with a median time from receipt to symptom onset of 45 days (IQR = 19-76 days). The number of infants who received nirsevimab was too low to stratify by duration from receipt; however, nirsevimab effectiveness is expected to decrease with increasing time after receipt because of antibody decay. Although nirsevimab uptake and the interval from receipt of nirsevimab were limited in this analysis, this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. John V. Williams reports institutional support from the National Institutes of Health (NIH); compensation for service on Quidel’s scientific advisory board through 2022 and service on GSK Independent Data Monitoring Committee; honorarium for Infectious Diseases of Children conference lecture; payments for participation on Independent Data Monitoring Committee, GSK, Data Safety Monitoring Board, and National Institute of Allergy and Infectious Diseases IMPAACT study. Janet A. Englund reports institutional support from GSK, and consulting fees from AstraZeneca, Meissa Vaccines, Moderna, and Sanofi Pasteur. Natasha B. Halasa reports grants from Sanofi and Quidel and consulting fees from Genetech. Mary Allen Staat reports institutional support from NIH and receipt of royalties from UpToDate. Geoffrey A. Weinberg reports institutional support from the New York State Department of Health AIDS Institute and honoraria from Merck & Co. for writing and editing textbook chapters in the Merck & Co. Merck Manual. Rangaraj Selvarangan reports grants from Hologic, BioFire, Becton Dickinson, Luminex, and Cepheid and honoraria for serving on a GSK advisory board. Marian G. Michaels reports support from NIH. Elizabeth P. Schlaudecker reports institutional support from Pfizer-BioNTech, support for attending a Pediatric Infectious Diseases Society meeting, uncompensated service on NIH Data Safety Monitoring Board and Division of Microbiology and Infectious Diseases Data Safety Monitoring Board, honorarium from Sanofi Pasteur, uncompensated membership in the World Society of Pediatric Infectious Diseases, and uncompensated service as committee chair for the Pediatric Infectious Diseases Society. Jennifer E. Schuster reports institutional support from NIH, Food and Drug Administration, and State of Missouri; speaking honoraria from the Missouri American Academy of Pediatrics; and payment for participation on the board of the Association of American Medical Colleges Advisory (AAMC) for a grant awarded to AAMC for vaccine confidence. Pedro A. Piedra reports grants or contracts from Icosavax, Mapp Biologics, Merck, Sanofi-Pasteur, GSK, Blue Lake Biotechnology, Shionogi, and IgM Biosciences; and reports consulting fees from Takada, Pfizer, Moderna, Merck, and Sanofi-Pasteur. No other potential conflicts of interest were disclosed.

Background: Respiratory syncytial virus (RSV) is the leading cause of hospitalization in US infants. Accurate estimates of severe RSV disease inform policy decisions for RSV prevention., Methods: We conducted prospective surveillance for children <5 years old with acute respiratory illness from 2016 to 2020 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested midturbinate nasal ± throat swabs by reverse transcription polymerase chain reaction for RSV and other respiratory viruses. We describe characteristics of children hospitalized with RSV, risk factors for ICU admission, and estimate RSV-associated hospitalization rates., Results: Among 13 524 acute respiratory illness inpatients <5 years old, 4243 (31.4%) were RSV-positive; 2751 (64.8%) of RSV-positive children had no underlying condition or history of prematurity. The average annual RSV-associated hospitalization rate was 4.0 (95% confidence interval [CI]: 3.8-4.1) per 1000 children <5 years, was highest among children 0 to 2 months old (23.8 [95% CI: 22.5-25.2] per 1000) and decreased with increasing age. Higher RSV-associated hospitalization rates were found in premature versus term children (rate ratio = 1.95 [95% CI: 1.76-2.11]). Risk factors for ICU admission among RSV-positive inpatients included: age 0 to 2 and 3 to 5 months (adjusted odds ratio [aOR] = 1.97 [95% CI: 1.54-2.52] and aOR = 1.56 [95% CI: 1.18-2.06], respectively, compared with 24-59 months), prematurity (aOR = 1.32 [95% CI: 1.08-1.60]) and comorbid conditions (aOR = 1.35 [95% CI: 1.10-1.66])., Conclusions: Younger infants and premature children experienced the highest rates of RSV-associated hospitalization and had increased risk of ICU admission. RSV prevention products are needed to reduce RSV-associated morbidity in young infants., (Copyright © 2024 by the American Academy of Pediatrics.)

SARS-CoV-2 infection in young children is often mild or asymptomatic; however, some children are at risk for severe disease. Data describing the protective effectiveness of COVID-19 mRNA vaccines against COVID-19-associated emergency department (ED) visits and hospitalization in this population are limited. Data from the New Vaccine Surveillance Network, a prospective population-based surveillance system, were used to estimate vaccine effectiveness using a test-negative, case-control design and describe the epidemiology of SARS-CoV-2 in infants and children aged 6 months-4 years during July 1, 2022-September 30, 2023. Among 7,434 children included, 5% received a positive SARS-CoV-2 test result, and 95% received a negative test result; 86% were unvaccinated, 4% had received 1 dose of any vaccine product, and 10% had received ≥2 doses. When compared with receipt of no vaccines among children, receipt of ≥2 COVID-19 mRNA vaccine doses was 40% effective (95% CI = 8%-60%) in preventing ED visits and hospitalization. These findings support existing recommendations for COVID-19 vaccination of young children to reduce COVID-19-associated ED visits and hospitalization., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Janet A. Englund reports institutional support from AstraZeneca, GSK, Pfizer-BioNTech, and Merck & Co. and consulting fees from Abbvie, AstraZeneca, Ark Biopharma, Meissa Vaccines, Moderna, Sanofi Pasteur, Shinogi, GSK, and Pfizer-BioNTech. John V. Williams reports institutional support from the National Institutes of Health (NIH) and compensation for service on Quidel’s Scientific Advisory Board through 2022 and on GSK’s Independent Data Monitoring Committee. Marian G. Michaels reports support from the National Institute of Allergy and Infectious Diseases, NIH, and Merck & Co.; receipt of lecture honoraria from the Transplant Alliance; support for meeting attendance from NIH, the Infectious Diseases Society of America, the Transplant Alliance, the American Society of Transplantation, and the International Transplant Nurses Association; participation on a National Institute of Allergy and Infectious Diseases Data Safety Monitoring Board; and services as Chair of the Infectious Diseases Committee of the International Pediatric Transplant Association. Geoffrey A. Weinberg reports institutional support from the New York State Department of Health AIDS Institute and honoraria from Merck & Co. for writing and editing textbook chapters in the Merck & Co. Manual. Natasha B. Halasa reports grants from Sanofi, Quidel, and Merck & Co. Elizabeth P. Schlaudecker reports institutional support from NIH and Pfizer-BioNTech, support for attending a Pediatric Infectious Diseases Society meeting, uncompensated service on NIH Data Safety Monitoring Board, honorarium for service on Sanofi Pasteur advisory board, uncompensated membership in the World Society of Pediatric Infectious Diseases, and uncompensated service as committee chair for the Pediatric Infectious Diseases Society. Mary Allen Staat reports institutional support from NIH, Merck & Co., Cepheid, and Pfizer-BioNTech and receipt of royalties from UpToDate. Peter G. Szilagyi reports a grant to the University of Rochester (subcontract to University of California at Los Angeles) No other potential conflicts of interest were disclosed.

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years † with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Janet A. Englund reports support from AstraZeneca, GSK (GlaxoSmithKline), and Pfizer, Inc., and consulting fees from Sanofi Pasteur, Meissa Vaccines, and AstraZeneca. Natasha B. Halasa reports grant support from Sanofi Pasteur and Quidel and an education grant from Genetech. Christopher J. Harrison reports institutional support from GSK, Merck, and Pfizer, Inc., and honoraria from Pediatric News. Rangaraj Selvarangan reports grants from Hologic, BioFire Diagnostics, Becton Dickinson, Luminex, and Cepheid and serves on the GSK advisory board. Geoffrey A. Weinberg reports consulting fees from ReViral and honoraria from Merck for writing textbook chapters in the Merck Manual. John V. Williams reports grant support from the National Institutes of Health (for work unrelated to the report), consulting fees from Quidel’s scientific advisory board, and honorarium from the Infectious Disease of Children for a conference presentation, participation on a GSK independent data monitoring committee and on a data safety monitoring board for the National Institute of Allergy and Infectious Diseases IMPAACT Study. No other potential conflicts of interest were disclosed.

Background: Predominance of 2 antigenically drifted influenza viruses during the 2019-2020 season offered an opportunity to assess vaccine effectiveness against life-threatening pediatric influenza disease from vaccine-mismatched viruses in the United States., Methods: We enrolled children aged <18 years admitted to the intensive care unit with acute respiratory infection across 17 hospitals. Respiratory specimens were tested using reverse-transcription polymerase chain reaction for influenza viruses and sequenced. Using a test-negative design, we estimated vaccine effectiveness comparing odds of vaccination in test-positive case patients vs test-negative controls, stratifying by age, virus type, and severity. Life-threating influenza included death or invasive mechanical ventilation, vasopressors, cardiopulmonary resuscitation, dialysis, or extracorporeal membrane oxygenation., Results: We enrolled 159 critically ill influenza case-patients (70% ≤8 years; 51% A/H1N1pdm09 and 25% B-Victoria viruses) and 132 controls (69% were aged ≤8 years). Among 56 sequenced A/H1N1pdm09 viruses, 29 (52%) were vaccine-mismatched (A/H1N1pdm09/5A+156K) and 23 (41%) were vaccine-matched (A/H1N1pdm09/5A+187A,189E). Among sequenced B-lineage viruses, majority (30 of 31) were vaccine-mismatched. Effectiveness against critical influenza was 63% (95% confidence interval [CI], 38% to 78%) and similar by age. Effectiveness was 75% (95% CI, 49% to 88%) against life-threatening influenza vs 57% (95% CI, 24% to 76%) against non-life-threating influenza. Effectiveness was 78% (95% CI, 41% to 92%) against matched A(H1N1)pdm09 viruses, 47% (95% CI, -21% to 77%) against mismatched A(H1N1)pdm09 viruses, and 75% (95% CI, 37% to 90%) against mismatched B-Victoria viruses., Conclusions: During a season when vaccine-mismatched influenza viruses predominated, vaccination was associated with a reduced risk of critical and life-threatening influenza illness in children., Competing Interests: Potential conflicts of interest. J. R. B. reports CDC program funds outside of the submitted work. B. M. C. reports payments to their institution from the National Institutes of Health (NIH), National Heart, Lung, and Blood Institutes, American Thoracic Society, and American Lung Association outside of the submitted work. M. W. H. reports royalties or licenses from Kiadis and participation on a data safety monitoring board or advisory board for La Jolla Pharmaceuticals. M. K. reports grants or contracts made to their institution from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01). R. A. N. reports funding to their institution as a subaward from the CDC and NIH. A. G. R. reports royalties or licenses from UpToDate for section editor pediatric critical care; payment for expert testimony for a sepsis-related case; unpaid role as a council member of the International Sepsis Forum; and unpaid role as medical board member of Families Fighting Flu. J. E. S. reports money paid to their institution from Merck and the NIH outside of the submitted work. N. J. T. reports payments to Penn State from the CDC outside of the submitted work. S. L. W. reports funds made to their institution from the NIH and Pennsylvania Department of Health outside of the submitted work and being a Data and Safety Monitoring Board (DSMB) member for the Oxy-PICU Clinical Trial. N. B. H. reports grants or contracts to their institution from Sanofi and Quidel; an educational grant funded by genetech; and healthcare-associated infections and vaccine donation from Sanofi for a vaccine study. J. R. H. reports DSMB for institutional study at the University of Minnesota (“Magnesium sulfate as adjuvant analgesia and its effect on opiate use by post-operative transplant patients in the pediatric ICU”) for magnesium sulfate as an investigational new drug per the US Food and Drug Administration with no financial reimbursements. 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., (Published by Oxford University Press for the Infectious Diseases Society of America 2022.)

In the fall of 2014, an outbreak of enterovirus D68 (EV-D68)-associated acute respiratory illness (ARI) occurred in the United States (1,2); before 2014, EV-D68 was rarely reported to CDC (2,3). In the United States, reported EV-D68 detections typically peak during late summer and early fall (3). EV-D68 epidemiology is not fully understood because testing in clinical settings seldom has been available and detections are not notifiable to CDC. To better understand EV-D68 epidemiology, CDC recently established active, prospective EV-D68 surveillance among pediatric patients at seven U.S. medical centers through the New Vaccine Surveillance Network (NVSN) (4). This report details a preliminary characterization of EV-D68 testing and detections among emergency department (ED) and hospitalized patients with ARI at all NVSN sites during July 1-October 31, 2017, and the same period in 2018. Among patients with ARI who were tested, EV-D68 was detected in two patients (0.8%) in 2017 and 358 (13.9%) in 2018. Continued active, prospective surveillance of EV-D68-associated ARI is needed to better understand EV-D68 epidemiology in the United States., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. W. Allan Nix reports a CDC employee invention report filing with CDC’s Technology Transfer Office for the pan EV-D68 real time reverse transcription–polymerase chain reaction assay and U.S. Patent Numbers 7247457, 7714122, and 8048630. W. Allan Nix and M. Steven Oberste report issuance of U.S. patent number 9,938,588 (Compositions and methods for detecting enterovirus D68). John Williams reports personal fees from Quidel and from GlaxoSmithKline, outside the submitted work. No other potential conflicts of interest were disclosed.