Tess Stopczynski

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

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Background: Human adenovirus (HAdV) is a common cause of pediatric acute respiratory illness (ARI), contributing to 5–13% of cases worldwide. Clinical manifestations vary by HAdV species and type; therefore, delineating type-specific disease presentations and understanding severity of specific HAdV types' disease may help develop targeted interventions. Methods: We conducted a multicenter, prospective study within the New Vaccine Surveillance Network to characterize HAdV types. Children <18 years old with ARI were enrolled in the emergency department or inpatient setting at 7 US children's hospitals from 1 December 2016 to 30 November 2019. Respiratory specimens were collected and tested for HAdV and other viruses. Subsequently, typing was conducted on HAdV specimens using single-plex real-time PCR assays targeting sequences in the hexon gene. Comparisons between HAdV types were performed to determine differences in characteristics and outcomes. Generalized linear mixed effects models were used to evaluate severity. Results: Among the 1843 HAdV-positive cases, 1402 specimens (76%) were typed. The most common types detected were HAdV-C1 (n = 439), HAdV-C2 (n = 393), and HAdV-B3 (n = 221). Children with HAdV-B7 (n = 78) had higher odds of severe outcomes compared to those with other HAdV types (aOR = 2.05; 95% CI: 1.24, 3.40). Symptom presentation varied across types within species B, C, and E; while all species had high frequency of upper respiratory symptoms, species B cases presented with a higher frequency of non-respiratory manifestations. Conclusions: Among children with HAdV-positive ARI, those with HAdV-B7 had higher odds of severe outcomes. These findings suggest heterogeneity in clinical presentation and severity among HAdV types, emphasizing the importance of HAdV type in future prevention and treatment strategies.

Importance: Despite national recommendations, antiviral prescribing in emergency departments (EDs) for children at higher risk of severe influenza, such as those younger than 5 years and those with specific underlying conditions, remains low. Objective: To assess whether there were changes in antiviral prescribing for children at higher risk of severe influenza in academic pediatric EDs before the COVID-19 pandemic (2016-2020) vs the late pandemic period (2021-2023). Design, Setting, and Participants: This multicenter, cross-sectional study included influenza-positive children younger than 18 years presenting to the ED at 1 of 7 US pediatric academic hospitals participating in the Centers for Disease Control and Prevention’s New Vaccine Surveillance Network. The analysis focused on children at higher risk of severe influenza seen in the ED from December 1, 2016, to June 30, 2023. Exposure: High risk of severe influenza. Main Outcomes and Measures: The primary outcome was antiviral prescribing. Children with influenza who met the criteria for higher risk of severe influenza were included. Antiviral prescribing practices were compared across the prepandemic and late pandemic periods. Mixed-effects logistic regression was used to identify factors associated with prescribing during the late pandemic period. Results: Of 3378 influenza-positive children (median [IQR] age, 3.9 [1.8-7.2] years), 2514 (74.4%; 1363 male [40.3%]) were classified as having higher risk of severe influenza during the prepandemic and late pandemic periods. Antiviral prescriptions decreased from 32.2% (622 of 1931 children) before the pandemic to 15.6% (91 of 583 children) in the late pandemic period, representing a 53% relative decrease. In the late pandemic period, symptom duration less than 2 days (adjusted odds ratio, 4.08; 95% CI, 2.49-6.71) and clinical influenza testing (adjusted odds ratio, 17.20; 95% CI, 4.08-72.37) were significantly associated with antiviral prescribing. Conclusions and Relevance: This multicenter, cross-sectional study of children with influenza in EDs found that, for children at higher risk of severe influenza illness, influenza antiviral prescribing decreased during the COVID-19 pandemic compared with prepandemic levels, despite unchanged treatment guidelines. Interventions are needed to support guideline-concordant prescribing in this population.

Background: Influenza contributes to a high burden of pediatric emergency department (ED) visits annually. Guidelines recommend outpatient antiviral treatment for children at higher risk of severe influenza and recommend considering treatment for those who present within 2 days of symptom onset. We describe antiviral prescription in children with influenza presenting to the ED.Methods: We analyzed data from the New Vaccine Surveillance Network (2016–2020), including children presenting to the ED and enrolled with confirmed influenza at one of seven pediatric academic centers. We compared characteristics of children prescribed antivirals to those who were not, using generalized estimating equations models to identify predictors of antiviral prescription. Children were considered at higher risk of severe influenza if they were < 5 years old or had an underlying condition.Results: Overall, 2472 (15%) of 16,915 enrolled children tested positive for influenza virus. Among these, 1931 (78%) were at higher risk of severe influenza; only 622 (32%) received an antiviral. Among 233 (9%) children not at high risk with symptom onset ≤ 2 days, 62 (27%) were prescribed an antiviral. Children prescribed an antiviral had a shorter duration of illness prior to presenting to the ED. For children at higher risk of severe influenza, odds of antiviral prescription were higher for those clinically tested for influenza and with underlying conditions.Conclusion: Clinical testing and having an underlying condition were associated with antiviral prescription in children at higher risk of severe influenza. However, only 1/3 of those at higher risk were prescribed an antiviral. Strategies to increase antiviral use for children at higher risk for influenza in the ED are needed.

Background: Human adenovirus (HAdV) is a common cause of pediatric acute respiratory illness (ARI). HAdV-B, -C, and -E species have been associated with ARI, though relative detection frequencies in United States (U.S.) and respective roles in symptomatic respiratory infections remain unclear. Methods: We conducted a multicenter, prospective viral surveillance study at 7 U.S. children’s hospitals comprising the New Vaccine Surveillance Network from January 12, 2016 to November 30, 2019. Children <18 years old in the emergency department or hospitalized with fever and/or respiratory symptoms were enrolled, and respiratory specimens were tested for HAdV and other viral pathogens. HAdV-positive specimens were subsequently typed using single-plex real-time PCR assays targeting sequences in the hexon gene. Demographics, clinical characteristics, and outcomes (hospitalization and supplemental oxygen use as severity indicators) were compared between HAdV-B and HAdV-C species. Results: Of the 29 381 children with ARI, 1843 (6.3%) had HAdV detected, with 1402 specimens (76.0%) successfully typed. HAdV-C was the most frequently detected species (73.0%), followed by HAdV-B (22.3%). Children with HAdV-C were younger than those with HAdV-B and more likely to have another respiratory pathogen. Among children without other detected respiratory pathogens, those with HAdV-C had lower odds of hospitalization compared with children with HAdV-B (aOR: 0.44, 95% CI, 0.27-0.73, P =.001). Conclusions: In our study among children seen in the emergency department or hospitalized with ARI, those with HAdV-C had lower odds of hospitalization compared with HAdV-B. These findings warrant further assessment to identify which HAdV types contribute to illness severity.

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

Background: Human parainfluenza viruses (PIV) are a major cause of acute respiratory infection (ARI) leading to hospitalization in young children. In order to quantify the burden of PIV hospitalizations and to evaluate the characteristics of children hospitalized with PIV by virus type, we used data from the New Vaccine Surveillance Network, a multicenter, active, prospective population-based surveillance network, enrolling children hospitalized for ARI (defined as fever and/or respiratory symptoms) at 7 U.S. children’s hospitals. Methods: The study period included December 1, 2016 through March 31, 2020. Data captured included demographic characteristics, clinical presentation, underlying medical conditions, discharge diagnoses, and virus detection by RT-PCR. Linear and logistic regression were used to compare descriptive and clinical characteristics among children. Population-based PIV-associated hospitalization rates were calculated by age group and PIV-type. Results: Of the 16,971 enrolled children with PIV virologic testing, 10,488 had only one respiratory virus detected, among whom 702 (7%) had positive testing for PIV without a co-detected virus (mean age [SD], 2.2 [3.2] years). Of these 702 children, 340 (48%) had underlying comorbidities, 139 (20%) had a history of prematurity, 121 (17%) were admitted to the ICU, and 23 (3%) required intubation. Overall, PIV hospitalization rates were highest in children aged 0-5 months, 1.91 hospitalizations per 1,000 children per year [95% CI, 1.61-2.23]; PIV-3 contributed to the highest rates in that age group, followed by PIV-1 and PIV-4: 1.08 [0.84-1.21], 0.42 [0.28-0.58] and 0.25 [0.15-0.37] per 1,000 children per year, respectively. Seasonal distribution of PIV-associated hospitalizations varied by type. Conclusions: PIV infection was associated with a substantial number of ARI hospitalizations in children aged 0-5 months. Results suggest that future PIV prevention strategies in the US that focus on younger children and protection against PIV-3, PIV-1, and PIV-4 might have the greatest impact on reducing PIV hospitalization burden.

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.

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