Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness-associated outpatient visits and hospitalizations from four VE networks during the 2024-25 influenza season (October 2024-February 2025). Among children and adolescents aged <18 years, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization in two networks. Preliminary estimates indicate that receipt of the 2024-2025 influenza vaccine reduced the likelihood of medically attended influenza and influenza-associated hospitalization. CDC recommends annual receipt of an age-appropriate influenza vaccine by all eligible persons aged ≥6 months as long as influenza viruses continue to circulate locally.

During 2023, the Centers for Disease Control and Prevention (CDC) recommended the first respiratory syncytial virus (RSV) immunizations intended for widespread use in the United States to prevent severe RSV illness in infants and older adults. CDC, in collaboration with federal, public health, and academic partners, is conducting evaluations of real-world effectiveness of recommended RSV immunization products in the United States. Similar frameworks for evaluation are being applied to RSV vaccines and nirsevimab, a long-acting preventative monoclonal antibody, to estimate product effectiveness. The overall goal of CDC's RSV immunization effectiveness program is to generate timely and robust evidence through observational studies to inform immunization product policy decisions and other measures related to RSV prevention and control. CDC is evaluating effectiveness through high-quality, well-controlled observational studies leveraging a variety of platforms that provide robust data to inform policy decisions.

IMPORTANCE: Increasing the understanding of vaccine effectiveness (VE) against levels of severe influenza in children could help increase uptake of influenza vaccination and strengthen vaccine policies globally. OBJECTIVE: To investigate VE in children by severity of influenza illness. DESIGN, SETTING, AND PARTICIPANTS: This case-control study with a test-negative design used data from 8 participating medical centers located in geographically different US states in the New Vaccine Surveillance Network from November 6, 2015, through April 8, 2020. Participants included children 6 months through 17 years of age who were hospitalized or presented to an emergency department (ED) with acute respiratory illness. EXPOSURES: Receipt of at least 1 dose of the current season's influenza vaccine. MAIN OUTCOMES AND MEASURES: Demographic and clinical characteristics of patients presenting to the hospital or ED with or without influenza were recorded and grouped by influenza vaccination status. Estimated VE against severe influenza illness was calculated using multiple measures to capture illness severity. Data were analyzed between June 1, 2022, and September 30, 2023. RESULTS: Among 15 728 children presenting for care with acute respiratory illness (8708 [55.4%] male; 13 450 [85.5%] 6 months to 8 years of age and 2278 [14.5%] 9-17 years of age), 2710 (17.2%) had positive influenza tests and 13 018 (82.8%) had negative influenza tests (controls). Of the influenza test-positive cases, 1676 children (61.8%) had an ED visit, 896 children (33.1%) required hospitalization for noncritical influenza, and 138 children (5.1%) required hospitalization for critical influenza. About half (7779 [49.5%]) of the children (both influenza test positive and test negative) were vaccinated. Receiving at least 1 influenza vaccine dose was estimated to have a VE of 55.7% (95% CI, 51.6%-59.6%) for preventing influenza-associated ED visits or hospitalizations among children of all ages. The estimated VE was similar across severity levels: 52.8% (95% CI, 46.6%-58.3%) for ED visits, 52.3% (95% CI, 44.8%-58.8%) for noncritical hospitalization, and 50.4% (95% CI, 29.7%-65.3%) for critical hospitalization. CONCLUSIONS AND RELEVANCE: Findings from this case-control study with a test-negative design involving children with a spectrum of influenza severity suggest that influenza vaccination protects children against all levels of severe influenza illness.

BACKGROUND: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children. METHODS: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network. The cohort consisted of children hospitalized with influenza A or B confirmed by clinical or research testing. The primary outcome was frequency of antiviral receipt during hospitalization. We used logistic regression to obtain adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with antiviral receipt. RESULTS: A total of 1213 children with laboratory-confirmed influenza were included. Overall, 652 children (53.8%) received an antiviral. Roughly 63.0% of children received clinical influenza testing. Among those with clinical testing, 67.4% received an antiviral. Factors associated with higher odds of antiviral receipt included hematologic (aOR = 1.76; 95% CI = 1.03-3.02) or oncologic/immunocompromising (aOR = 2.41; 95% CI = 1.13-5.11) disorders, prehospitalization antiviral receipt (aOR = 2.34; 95% CI = 1.49-3.67), clinical influenza testing (aOR = 3.07; 95% CI = 2.28-4.14), and intensive care unit admission (aOR = 1.53; 95% CI = 1.02-2.29). Symptom duration >2 days was associated with lower odds of antiviral treatment (aOR = 0.40; 95% CI = .30-.52). Antiviral receipt varied by site with a 5-fold difference across sites. CONCLUSIONS: Almost half of children hospitalized with influenza did not receive antivirals. Additional efforts to understand barriers to guideline adherence are crucial for optimizing care in children hospitalized with influenza.

IMPORTANCE: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness. OBJECTIVE: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without nirsevimab receipt. DESIGN, SETTING, AND PARTICIPANTS: This study included a prospective population-based surveillance for medically attended ARI with systematic molecular testing for RSV and whole-genome sequencing of RSV positive samples, as well as a test-negative case-control design to estimate nirsevimab effectiveness. The study was conducted in 7 academic pediatric medical centers in the United States with data from RSV seasons (September 1 through April 30) in 2017 through 2024. Participants were children younger than 5 years with medically attended ARI. EXPOSURE: For the nirsevimab effectiveness analyses, nirsevimab receipt among infants younger than 8 months as of or born after October 1, 2023. MAIN OUTCOME AND MEASURE: Medically attended RSV-associated ARI. RESULTS: Overall, 28 689 children younger than 5 years with medically attended ARI were enrolled, including 9536 during September 1, 2023, through April 30, 2024, and 19 153 during the same calendar period of 2017-2020. Of these children, 16 196 (57%) were male, and 12 444 (43.4) were female; the median (IQR) age was 15 (6-29) months. During 2023-2024, the proportion of children with RSV was 23% (2199/9490) among all medically attended episodes, similar to 2017-2020. RSV-associated hospitalization rates in 2023-2024 were similar to average 2017-2020 seasonal rates with 5.0 (95% CI, 4.6-5.3) per 1000 among children younger than 5 years; the highest rates were among children aged 0 to 2 months (26.6; 95% CI, 23.0-30.2). Low maternal RSV vaccine uptake precluded assessment of effectiveness. Overall, 10 of 765 case patients (1%) who were RSV positive and 126 of 851 control patients (15%) who were RSV negative received nirsevimab. Nirsevimab effectiveness was 89% (95% CI, 79%-94%) against medically attended RSV-associated ARI and 93% (95% CI, 82%-97%) against RSV-associated hospitalization. Among 229 sequenced specimens, there were no differences in nirsevimab binding site mutations by infant nirsevimab receipt status. CONCLUSIONS AND RELEVANCE: This analysis documented the continued high burden of medically attended RSV-associated ARI among young children in the US. There is a potential for substantial public health impact with increased and equitable prevention product coverage in future seasons.

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.

BACKGROUND: The COVID-19 pandemic raised unprecedented challenges to vaccinating children. This multi-center study aimed to compare on-time vaccination of children before and during the COVID-19 pandemic and identify key factors associated with on-time vaccination. METHODS: This study was conducted among children aged 0-6 years enrolled in the New Vaccine Surveillance Network at seven geographically diverse U.S. academic medical centers. Children with acute respiratory illness or acute gastroenteritis were enrolled from emergency department and inpatient settings; healthy control subjects were enrolled from primary care practices. Vaccination data were collected and verified from patient medical records, immunization information systems, and/or provider documentation. On-time vaccination according to Advisory Committee on Immunization Practices recommendations was compared between pre-pandemic (December 2018-February 2020) and pandemic (March 2020-August 2021) periods using bivariate and multivariable analyses, adjusting for key demographic, clinical, and study characteristics. RESULTS: A total of 24,713 children were included in the analytic sample (non-Hispanic 73.4 %; White 51.0 %; publicly insured 69.0 %). On-time vaccination declined between the pre-pandemic (67.3 %) and pandemic (65.4 %) periods (Adjusted Odds Ratio 0.89, 95 % CI 0.84-0.95). The largest declines were observed among children who were < 12 months, male, Black, publicly insured, or whose mothers had a high school-equivalent education or less. The pandemic impact also varied by vaccine type and study site. CONCLUSIONS: This multi-center study revealed a relatively modest overall reduction in on-time vaccination, which may reflect multilevel efforts to address pandemic-associated challenges. However, some patient subgroups and sites experienced greater reductions in on-time vaccination, highlighting the importance of tailoring interventions to increase equitable vaccine delivery, access, and acceptance across populations and communities.

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.

BACKGROUND: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities. METHODS: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses. We estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 prepandemic seasons (2016-2020) to those hospitalized in 2021 or 2022. RESULTS: There was no difference in median age or age distribution between prepandemic and 2021 seasons. Median age of children hospitalized with RSV was higher in 2022 (9.6 months vs 6.0 months, P < .001). RSV-associated hospitalization rates were higher in 2021 and 2022 than the prepandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37-2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in prepandemic seasons (P < .001 and P = .003, respectively), but there was no difference in the proportion hypoxemic, mechanically ventilated, or admitted to intensive care. CONCLUSIONS: The atypical 2021 and 2022 RSV seasons resulted in higher hospitalization rates with similar disease severity to prepandemic seasons.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established. METHODS: During 2016-2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction. RESULTS: Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A-positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally. CONCLUSIONS: Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes.

IMPORTANCE: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown. OBJECTIVE: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings. DESIGN, SETTING, AND PARTICIPANTS: Children younger than 18 years presenting to the ED or inpatient settings with fever and/or respiratory symptoms at 7 US pediatric medical centers affiliated with the Centers for Disease Control and Prevention-sponsored New Vaccine Surveillance Network from December 1, 2016, to March 31, 2020, were included in this cohort study. Nasal and/or throat swabs were collected for research molecular testing for influenza, regardless of clinical testing. Data, including ICD-10 discharge diagnoses and clinical testing for influenza, were obtained through medical record review. Data analysis was performed in August 2023. MAIN OUTCOMES AND MEASURES: The accuracy of ICD-10-coded discharge diagnoses was characterized using molecular clinical or research laboratory test results as reference. Measures included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Estimates were stratified by setting (ED vs inpatient) and age (0-1, 2-4, and 5-17 years). RESULTS: A total of 16 867 children in the ED (median [IQR] age, 2.0 [0.0-4.0] years; 9304 boys [55.2%]) and 17 060 inpatients (median [IQR] age, 1.0 [0.0-4.0] years; 9798 boys [57.4%]) were included. In the ED, ICD-10 influenza diagnoses were highly specific (98.0%; 95% CI, 97.8%-98.3%), with high PPV (88.6%; 95% CI, 88.0%-89.2%) and high NPV (85.9%; 95% CI, 85.3%-86.6%), but sensitivity was lower (48.6%; 95% CI, 47.6%-49.5%). Among inpatients, specificity was 98.2% (95% CI, 98.0%-98.5%), PPV was 82.8% (95% CI, 82.1%-83.5%), sensitivity was 70.7% (95% CI, 69.8%-71.5%), and NPV was 96.5% (95% CI, 96.2%-96.9%). Accuracy of ICD-10 diagnoses varied by patient age, influenza season definition, time between disease onset and testing, and clinical setting. CONCLUSIONS AND RELEVANCE: In this large cohort study, influenza ICD-10 discharge diagnoses were highly specific but moderately sensitive in identifying laboratory-confirmed influenza; the accuracy of influenza diagnoses varied by clinical and epidemiological factors. In the ED and inpatient settings, an ICD-10 diagnosis likely represents a true-positive influenza case.

OBJECTIVE: To assess medical costs of hospitalizations and emergency department (ED) care associated with respiratory syncytial virus (RSV) disease in children enrolled in the New Vaccine Surveillance Network. STUDY DESIGN: We used accounting and prospective surveillance data from six pediatric health systems to assess direct medical costs from laboratory-confirmed RSV-associated hospitalizations (n=2,007) and ED visits (n=1,267) from 2016 through 2019 among children aged <5 years. We grouped costs into categories relevant to clinical care and administrative billing practices. We examined RSV-associated medical costs by care setting using descriptive and bivariate analyses. We assessed associations between known RSV risk factors and hospitalization costs and length of stay (LOS) using chi-square tests of association. RESULTS: The median cost was $7,100 (IQR: $4,006-$13,355) per hospitalized child and $503 (IQR: $387-$930) per ED visit. Eighty percent (n=2,628) of our final sample were children aged <2 years. Fewer weeks' gestational age (GA) was associated with higher median costs in hospitalized children [p<0.001, ≥37 weeks' GA: $6,840 ($3,905-$12,450); 29-36 weeks' GA: $7,721 ($4,362-$15,274); <29 w weeks' GA: $9,131 ($4,518-$19,924)]. Full-term infants accounted for 70% of the total expenditures in our sample. Almost three quarters of the healthcare dollars spent originated in children under 12 months of age; the primary age group targeted by recommended RSV prophylactics. CONCLUSIONS: Reducing the cost burden for RSV-associated medical care in young children will require prevention of RSV in all young children, not just high-risk infants. Newly available maternal vaccine and immunoprophylaxis products could substantially reduce RSV-associated medical costs.

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.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

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.

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.

On February 1, 2022, the U.S. Virgin Islands (USVI) Department of Health (VIDOH) was notified of a confirmed case of Legionnaires disease in an adult U.S. resident (Figure). The patient, a man aged 55 years, returned to his U.S. state of residence from leisure travel in USVI on January 22 and developed a cough, shortness of breath, and fatigue on January 23. On January 29, he was hospitalized for shortness of breath and received a positive SARS-CoV-2 test result at admission. The combination of the patient’s symptoms and recent travel history prompted administration of a urinary antigen test (UAT) for Legionnaires disease specific to Legionella pneumophila serogroup 1 (Lp1); a positive result was returned on January 31. Inpatient treatment administered for COVID-19 pneumonia and Legionnaires disease included remdesivir, oral levofloxacin, oral and intravenous steroid therapy, and as-needed use of a bronchodilator inhaler and an expectorant. Remdesivir was discontinued during inpatient treatment because of elevated liver enzymes. The patient recovered and was discharged on February 2.

BACKGROUND: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the COVID-19 pandemic in the United States are limited. METHODS: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as March 1-December 31, 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014-February 2020 trends. We conducted secondary analysis of a healthcare database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic. RESULTS: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated non-pharmaceutical-interventions (NPIs). Significant declines were observed across all age, race groups and surveillance sites for S pneumoniae and H influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years. CONCLUSIONS: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing.

More than 20 years have elapsed since the September 11, 2001 (9/11) terrorist attacks on the World Trade Center (WTC), Pentagon and at Shanksville, PA. Many persons continue to suffer a variety of physical and mental health conditions following their exposures to a mixture of incompletely characterized toxicants and psychological stressors at the terrorist attack sites. Primary care and specialized clinicians should ask patients who may have been present at any of the 9/11 sites about their 9/11 exposures, especially patients with cancer, respiratory symptoms, chronic rhinosinusitis, gastroesophageal reflux disease, psychiatric symptoms, and substance use disorders. Clinicians, especially those in the NY metropolitan area, should know how to evaluate, diagnose, and treat patients with conditions that could be associated with exposure to the 9/11 attacks and its aftermath. As such, this issue of Archives contains a series of updates to clinical best practices relevant to medical conditions whose treatment is covered by the WTC Health Program. This first paper in the 14-part series describes the purpose of this series, defines the WTC Health Program and its beneficiaries, and explains how relevant Clinical Practice Guidelines were identified. This paper also reminds readers that because physical and mental health conditions are often intertwined, a coordinated approach to care usually works best and referral to health centers affiliated with the WTC Health Program may be necessary, since all such Centers offer multidisciplinary care.

In December 2020, an interim recommendation for the use of Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years was made under Food and Drug Administration's Emergency Use Authorization. In preparation for Biologics License Application approval, we conducted a systematic review and meta-analysis to inform the U.S. Centers for Disease Control and Prevention's Advisory Committee for Immunization Practice's (ACIP) decision-making for a standard recommendation. We conducted a rapid systematic review and meta-analysis of Pfizer-BioNTech vaccine effectiveness (VE) against symptomatic COVID-19, hospitalization due to COVID-19, death due to COVID-19, and asymptomatic SARS-CoV-2 infection. We identified studies through August 20, 2021 from an ongoing systematic review conducted by the International Vaccine Access Center and the World Health Organization. We evaluated each study for risk of bias using the Newcastle-Ottawa Scale. Pooled estimates were calculated using meta-analysis. The body of evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We identified 80 articles, selected 35 for full-text review, and included 26. The pooled VE of Pfizer-BioNTech COVID-19 vaccine was 92.4% (95% CI: 87.5%-95.3%) against symptomatic COVID-19 with moderate evidence certainty (eight studies), 94.3% (95% CI: 87.9%-97.3%) against hospitalization due to COVID-19 with moderate certainty (eight studies), 96.1% (95% CI: 91.5%-98.2%) against death due to COVID-19 with moderate certainty (four studies), and 89.3% (88.4%-90.1%) against asymptomatic SARS-CoV-2 infection with very low certainty (two studies). The Pfizer-BioNTech COVID-19 vaccine demonstrated high effectiveness in all pre-specified outcomes and extended knowledge of the vaccine's benefits to outcomes and populations not informed by the RCTs. Use of an existing systematic review facilitated a rapid meta-analysis to inform an ACIP policy decision. This approach can be utilized as additional COVID-19 vaccines are considered for standard recommendations by ACIP.

Increases in severe respiratory illness and acute flaccid myelitis (AFM) among children and adolescents resulting from enterovirus D68 (EV-D68) infections occurred biennially in the United States during 2014, 2016, and 2018, primarily in late summer and fall. Although EV-D68 annual trends are not fully understood, EV-D68 levels were lower than expected in 2020, potentially because of implementation of COVID-19 mitigation measures (e.g., wearing face masks, enhanced hand hygiene, and physical distancing) (1). In August 2022, clinicians in several geographic areas notified CDC of an increase in hospitalizations of pediatric patients with severe respiratory illness and positive rhinovirus/enterovirus (RV/EV) test results.* Surveillance data were analyzed from multiple national data sources to characterize reported trends in acute respiratory illness (ARI), asthma/reactive airway disease (RAD) exacerbations, and the percentage of positive RV/EV and EV-D68 test results during 2022 compared with previous years. These data demonstrated an increase in emergency department (ED) visits by children and adolescents with ARI and asthma/RAD in late summer 2022. The percentage of positive RV/EV test results in national laboratory-based surveillance and the percentage of positive EV-D68 test results in pediatric sentinel surveillance also increased during this time. Previous increases in EV-D68 respiratory illness have led to substantial resource demands in some hospitals and have also coincided with increases in cases of AFM (2), a rare but serious neurologic disease affecting the spinal cord. Therefore, clinicians should consider AFM in patients with acute flaccid limb weakness, especially after respiratory illness or fever, and ensure prompt hospitalization and referral to specialty care for such cases. Clinicians should also test for poliovirus infection in patients suspected of having AFM because of the clinical similarity to acute flaccid paralysis caused by poliovirus. Ongoing surveillance for EV-D68 is critical to ensuring preparedness for possible future increases in ARI and AFM.

IMPORTANCE: Understanding risk factors for hospitalization in vaccinated persons and the association of COVID-19 vaccines with hospitalization rates is critical for public health efforts to control COVID-19. OBJECTIVE: To determine characteristics of COVID-19-associated hospitalizations among vaccinated persons and comparative hospitalization rates in unvaccinated and vaccinated persons. DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2021, to April 30, 2022, patients 18 years or older with laboratory-confirmed SARS-CoV-2 infection were identified from more than 250 hospitals in the population-based COVID-19-Associated Hospitalization Surveillance Network. State immunization information system data were linked to cases, and the vaccination coverage data of the defined catchment population were used to compare hospitalization rates in unvaccinated and vaccinated individuals. Vaccinated and unvaccinated patient characteristics were compared in a representative sample with detailed medical record review; unweighted case counts and weighted percentages were calculated. EXPOSURES: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test result within 14 days before or during hospitalization. MAIN OUTCOMES AND MEASURES: COVID-19-associated hospitalization rates among vaccinated vs unvaccinated persons and factors associated with COVID-19-associated hospitalization in vaccinated persons were assessed. RESULTS: Using representative data from 19509 hospitalizations (see Table 1 for demographic information), monthly COVID-19-associated hospitalization rates ranged from 3.5 times to 17.7 times higher in unvaccinated persons than vaccinated persons regardless of booster dose status. From January to April 2022, when the Omicron variant was predominant, hospitalization rates were 10.5 times higher in unvaccinated persons and 2.5 times higher in vaccinated persons with no booster dose, respectively, compared with those who had received a booster dose. Among sampled cases, vaccinated hospitalized patients with COVID-19 were older than those who were unvaccinated (median [IQR] age, 70 [58-80] years vs 58 [46-70] years, respectively; P<.001) and more likely to have 3 or more underlying medical conditions (1926 [77.8%] vs 4124 [51.6%], respectively; P<.001). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US adults hospitalized with COVID-19, unvaccinated adults were more likely to be hospitalized compared with vaccinated adults; hospitalization rates were lowest in those who had received a booster dose. Hospitalized vaccinated persons were older and more likely to have 3 or more underlying medical conditions and be long-term care facility residents compared with hospitalized unvaccinated persons. The study results suggest that clinicians and public health practitioners should continue to promote vaccination with all recommended doses for eligible persons.

In April 2021, we assessed mRNA vaccine effectiveness (VE) in the context of a COVID-19 outbreak in a skilled nursing facility. Among 28 cases, genomic sequencing was performed on four specimens on four different patients, and all were classified by sequence analysis as the Beta (B.1.351) variant. Adjusted VE among residents was 65% (95% Confidence Interval: 25-84%). These findings underscore the importance of vaccination for prevention of COVID-19 in skilled nursing facilities.

Three COVID-19 vaccines are currently approved under a Biologics License Application (BLA) or authorized under an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) and recommended for primary vaccination by the Advisory Committee on Immunization Practices (ACIP) in the United States: the 2-dose mRNA-based Pfizer-BioNTech/Comirnaty and Moderna COVID-19 vaccines and the single-dose adenovirus vector-based Janssen (Johnson & Johnson) COVID-19 vaccine (1,2) (Box 1). In August 2021, FDA amended the EUAs for the two mRNA COVID-19 vaccines to allow for an additional primary dose in certain immunocompromised recipients of an initial mRNA COVID-19 vaccination series (1). During September-October 2021, FDA amended the EUAs to allow for a COVID-19 vaccine booster dose following a primary mRNA COVID-19 vaccination series in certain recipients aged ≥18 years who are at increased risk for serious complications of COVID-19 or exposure to SARS-CoV-2 (the virus that causes COVID-19), as well as in recipients aged ≥18 years of Janssen COVID-19 vaccine (1) (Table). For the purposes of these recommendations, an additional primary (hereafter additional) dose refers to a dose of vaccine administered to persons who likely did not mount a protective immune response after initial vaccination. A booster dose refers to a dose of vaccine administered to enhance or restore protection by the primary vaccination, which might have waned over time. Health care professionals play a critical role in COVID-19 vaccination efforts, including for primary, additional, and booster vaccination, particularly to protect patients who are at increased risk for severe illness and death.

The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is a lipid nanoparticle-formulated, nucleoside mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. In December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) as well as an interim recommendation for use among persons aged ≥16 years by the Advisory Committee on Immunization Practices (ACIP) (1). In May 2021, the EUA and interim ACIP recommendations for Pfizer-BioNTech COVID-19 vaccine were extended to adolescents aged 12-15 years (2). During December 14, 2020-September 1, 2021, approximately 211 million doses of Pfizer-BioNTech COVID-19 vaccine were administered in the United States.* On August 23, 2021, FDA approved a Biologics License Application for use of the Pfizer-BioNTech COVID-19 vaccine, Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (3). The ACIP COVID-19 Vaccines Work Group's conclusions regarding the evidence for the Pfizer-BioNTech COVID-19 vaccine were presented to ACIP at a public meeting on August 30, 2021. To guide its deliberations regarding the Pfizer-BioNTech COVID-19 vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,(†) and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(§) In addition to initial clinical trial data, ACIP considered new information gathered in the 8 months since issuance of the interim recommendation for Pfizer-BioNTech COVID-19 vaccine, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. The additional information increased certainty that benefits from prevention of asymptomatic infection, COVID-19, and associated hospitalization and death outweighs vaccine-associated risks. On August 30, 2021, ACIP issued a recommendation(¶) for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19.

Clinical trials of COVID-19 vaccines currently authorized for emergency use in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) indicate that these vaccines have high efficacy against symptomatic disease, including moderate to severe illness (1-3). In addition to clinical trials, real-world assessments of COVID-19 vaccine effectiveness are critical in guiding vaccine policy and building vaccine confidence, particularly among populations at higher risk for more severe illness from COVID-19, including older adults. To determine the real-world effectiveness of the three currently authorized COVID-19 vaccines among persons aged ≥65 years during February 1-April 30, 2021, data on 7,280 patients from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed with vaccination coverage data from state immunization information systems (IISs) for the COVID-NET catchment area (approximately 4.8 million persons). Among adults aged 65-74 years, effectiveness of full vaccination in preventing COVID-19-associated hospitalization was 96% (95% confidence interval [CI] = 94%-98%) for Pfizer-BioNTech, 96% (95% CI = 95%-98%) for Moderna, and 84% (95% CI = 64%-93%) for Janssen vaccine products. Effectiveness of full vaccination in preventing COVID-19-associated hospitalization among adults aged ≥75 years was 91% (95% CI = 87%-94%) for Pfizer-BioNTech, 96% (95% CI = 93%-98%) for Moderna, and 85% (95% CI = 72%-92%) for Janssen vaccine products. COVID-19 vaccines currently authorized in the United States are highly effective in preventing COVID-19-associated hospitalizations in older adults. In light of real-world data demonstrating high effectiveness of COVID-19 vaccines among older adults, efforts to increase vaccination coverage in this age group are critical to reducing the risk for COVID-19-related hospitalization.

During September 14–October 1, 2018, the Minnesota Department of Health (MDH) was notified of six children hospitalized in the Minneapolis-St. Paul region with symptoms consistent with acute flaccid myelitis (AFM). A confirmed case of AFM is defined as acute onset of flaccid limb weakness with magnetic resonance image indicating spinal cord lesions largely restricted to gray matter and spanning one or more vertebral segments (1). All six cases were confirmed by CDC. After a cluster of three cases occurred in 2014, an average of fewer than one AFM case per year had been reported to MDH.

Introduction The purpose of this article is to present the collective experiences of six federally-funded critical congenital heart disease (CCHD) newborn screening implementation projects to assist federal and state policy makers and public health to implement CCHD screening. Methods A qualitative assessment and summary from six demonstration project grantees and other state representatives involved in the implementation of CCHD screening programs are presented in the following areas: legislation, provider and family education, screening algorithms and interpretation, data collection and quality improvement, telemedicine, home and rural births, and neonatal intensive care unit populations. Results The most common challenges to implementation include: lack of uniform legislative and statutory mandates for screening programs, lack of funding/resources, difficulty in screening algorithm interpretation, limited availability of pediatric echocardiography, and integrating data collection and reporting with existing newborn screening systems. Identified solutions include: programs should consider integrating third party insurers and other partners early in the legislative/statutory process; development of visual tools and language modification to assist in the interpretation of algorithms, training programs for adult sonographers to perform neonatal echocardiography, building upon existing newborn screening systems, and using automated data transfer mechanisms. Discussion Continued and expanded surveillance, research, prevention and education efforts are needed to inform screening programs, with an aim to reduce morbidity, mortality and other adverse consequences for individuals and families affected by CCHD.

BACKGROUND: The disasters at Seveso, Three Mile Island, Bhopal, Chernobyl, the World Trade Center (WTC) and Fukushima had historic health and economic sequelae for large populations of workers, responders and community members. METHODS: Comparative data from these events were collected to derive indications for future preparedness. Information from the primary sources and a literature review addressed: i) exposure assessment; ii) exposed populations; iii) health surveillance; iv) follow-up and research outputs; v) observed physical and mental health effects; vi) treatment and benefits; and vii) outreach activities. RESULTS: Exposure assessment was conducted in Seveso, Chernobyl and Fukushima, although none benefited from a timely or systematic strategy, yielding immediate and sequential measurements after the disaster. Identification of exposed subjects was overall underestimated. Health surveillance, treatment and follow-up research were implemented in Seveso, Chernobyl, Fukushima, and at the WTC, mostly focusing on the workers and responders, and to a lesser extent on residents. Exposure-related physical and mental health consequences were identified, indicating the need for a long-term health care of the affected populations. Fukushima has generated the largest scientific output so far, followed by the WTCHP and Chernobyl. Benefits programs and active outreach figured prominently in only the WTC Health Program. The analysis of these programs yielded the following lessons: 1) Know who was there; 2) Have public health input to the disaster response; 3) Collect health and needs data rapidly; 4) Take care of the affected; 5) Emergency preparedness; 6) Data driven, needs assessment, advocacy. CONCLUSIONS: Given the long-lasting health consequences of natural and man-made disasters, health surveillance and treatment programs are critical for management of health conditions, and emergency preparedness plans are needed to prevent or minimize the impact of future threats.

Posttraumatic stress disorder (PTSD) is a debilitating and often chronic psychiatric disorder. Following the 9/11/2001 World Trade Center (WTC) attacks, thousands of individuals were involved in rescue, recovery and clean-up efforts. While a growing body of literature has documented the prevalence and correlates of PTSD in WTC responders, no study has evaluated predominant typologies of PTSD in this population. Participants were 4352 WTC responders with probable WTC-related DSM-IV PTSD. Latent class analyses were conducted to identify predominant typologies of PTSD symptoms and associated correlates. A 3-class solution provided the optimal representation of latent PTSD symptom typologies. The first class, labeled "High-Symptom (n = 1,973, 45.3%)," was characterized by high probabilities of all PTSD symptoms. The second class, "Dysphoric (n = 1,371, 31.5%)," exhibited relatively high probabilities of emotional numbing and dysphoric arousal (e.g., sleep disturbance). The third class, "Threat (n = 1,008, 23.2%)," was characterized by high probabilities of re-experiencing, avoidance and anxious arousal (e.g., hypervigilance). Compared to the Threat class, the Dysphoric class reported a greater number of life stressors after 9/11/2001 (OR = 1.06). The High-Symptom class was more likely than the Threat class to have a positive psychiatric history before 9/11/2001 (OR = 1.7) and reported a greater number of life stressors after 9/11/2001 (OR = 1.1). The High-Symptom class was more likely than the Dysphoric class, which was more likely than the Threat class, to screen positive for depression (83% > 74% > 53%, respectively), and to report greater functional impairment (High-Symptom > Dysphoric [Cohen d = 0.19], Dysphoric > Threat [Cohen d = 0.24]). These results may help inform assessment, risk stratification, and treatment approaches for PTSD in WTC and disaster responders.