Background Human adenovirus (HAdV) is commonly associated with acute respiratory illnesses (ARI) in children and is also frequently co-detected with other viral pathogens. We compared clinical presentation and outcomes in young children with HAdV detected alone vs co-detected with other respiratory viruses. Methods We used data from a multicenter, prospective, viral surveillance study of children seen in the emergency department and inpatient pediatric settings at seven US sites. Children less than 18 years old with fever and/or respiratory symptoms were enrolled between 12/1/16 and 10/31/18 and tested by molecular methods for HAdV, human rhinovirus/enterovirus (HRV/EV), respiratory syncytial virus (RSV), parainfluenza (PIV, types 1–4), influenza (flu, types A-C), and human metapneumovirus (HMPV). Our primary measure of illness severity was hospitalization; among hospitalized children, secondary severity outcomes included oxygen support and length of stay (LOS). Results Of the 18,603 children enrolled, HAdV was detected in 1,136 (6.1%), among whom 646 (56.9%) had co-detection with at least one other respiratory virus. HRV/EV (n = 293, 45.3%) and RSV (n = 123, 19.0%) were the most frequent co-detections. Children with HRV/EV (aOR = 1.61; 95% CI = [1.11–2.34]), RSV (aOR = 4.48; 95% CI = [2.81–7.14]), HMPV (aOR = 3.39; 95% CI = [1.69–6.77]), or ≥ 2 co-detections (aOR = 1.95; 95% CI = [1.14–3.36]) had higher odds of hospitalization compared to children with HAdV alone. Among hospitalized children, HAdV co-detection with RSV or HMPV was each associated with higher odds of oxygen support, while co-detection with PIV or influenza viruses was each associated with higher mean LOS. Conclusions HAdV co-detection with other respiratory viruses was associated with greater disease severity among children with ARI compared to HAdV detection alone.

BackgroundPatterns of respiratory syncytial virus (RSV) co-detection with other viruses may have been disrupted during the coronavirus disease 2019 (COVID-19) pandemic, but the clinical impact of viral co-detections with RSV is not well-established. We aimed to explore the frequency and clinical outcomes associated with RSV single detection and co-detection before and during the pandemic.MethodsWe conducted a single-center retrospective cohort study of all children and adults with respiratory samples tested using a respiratory pathogen panel (RPP; 01/01/2018–11/30/2022), a provider-ordered polymerase chain reaction–based assay that detects respiratory pathogens. We stratified our cohort into age groups: 0–4, 5–17, 18–64, and ≥65 years old. Among RSV-positive samples, we compared the proportion of samples with single RSV detection before and during the pandemic and the patterns of specific viral co-detections. We compared the odds of hospitalization, oxygen use, intensive care unit admission, and intubation between individuals with RSV single detection and those with co-detection.ResultsAmong 57,940 samples collected during the study period, 3,986 (6.9%) were RSV-positive. RSV was co-detected with at least one other virus in 1,231/3,158 (39.0%), 104/348 (29.9%), 49/312 (15.7%), and 21/168 (12.5%) of samples from individuals 0–4, 5–17, 18–64, and ≥65 years old, respectively. The relative frequencies of RSV single detection and co-detection were comparable before and during the pandemic except in children 0–4 years old, in whom single RSV detections were more prevalent before (63.7%) than during (59.5%) the pandemic (p=0.021). In children 0–4 years old, RSV co-detection was associated with lower odds of hospitalization compared to single RSV detection, and RSV co-detection with parainfluenza viruses or human rhinovirus/enterovirus was associated with significantly lower odds of hospitalization, while RSV/SARS-CoV-2 co-detection was associated with higher odds of ICU admission. In adults ≥65 years old, RSV co-detection was associated with lower odds of oxygen use.ConclusionThe proportion of RSV co-detection did not appreciably vary before and during the pandemic, except in young children, though the combinations of co-detected viruses did vary. Our findings suggest that the clinical impact of RSV co-detection with other viruses may be age-associated and virus-specific.

Background Adenovirus (AdV) is a common cause of acute respiratory illness (ARI). Multiple respiratory AdV types have been identified in humans, but it remains unclear which are the most common in U.S. children with ARI. Methods We conducted a multicenter, prospective viral surveillance study at seven U.S. children’s hospitals, the New Vaccine Surveillance Network, during 12/1/16–11/30/19, prior to the COVID-19 pandemic. Children < 18 years of age seen in the emergency department or hospitalized with fever and/or respiratory symptoms were enrolled, and mid-turbinate nasal +/- throat swabs were tested using multiplex respiratory pathogen assays or real time polymerase chain reaction (PCR) test for AdV, respiratory syncytial virus (RSV), human metapneumovirus, rhinovirus/enterovirus (RV), influenza, parainfluenza viruses, and endemic coronaviruses. AdV-positive specimens were subsequently typed using single-plex qPCR assays targeting sequences in the hexon gene specific for types 1-7, 11, 14, 16 and 21. Demographics, clinical characteristics, and outcomes were compared between AdV types. Results Of 29,381 enrolled children, 2,106 (7.2%) tested positive for AdV. The distribution of types among the 1,330 (63.2%) successfully typed specimens were as follows: 31.7% AdV-2, 28.9% AdV-1, 15.3% AdV-3, 7.9% AdV-5, 5.9% AdV-7, 1.4% AdV-4, 1.2% AdV-6, 0.5% AdV-14, 0.2% AdV-21, 0.1% AdV-11, and 7.0% ≥1 AdV type. Most children with AdV-1 or AdV-2 detection were < 5 years of age (Figure 1a). Demographic and clinical characteristics varied by AdV types, including age, race/ethnicity, smoke exposure, daycare/school attendance, and hospitalization (Table 1). Co-detection with other viruses was common among all AdV types, with RV and RSV being the most frequently co-detected (Figure 1b). Fever and cough were the most common symptoms for all AdV types (Figure 2). Children with AdV-7 detected as single pathogen had higher odds of hospitalization (adjusted odds ratio 6.34 [95% CI: 3.10, 12.95], p= 0.027). Conclusion AdV-2 and AdV-1 were the most frequently detected AdV types among children over the 3-year study period. Notable clinical heterogeneity of the AdV types warrants further surveillance studies to identify AdV types that could be targeted for pediatric vaccine development. Disclosures Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|National Institute of Health: Grant/Research Support|Uptodate: Royalties Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Mary E. Moffatt, M.D., Becton and Dickinson and Company: Stocks/Bonds|Biogen: Stocks/Bonds|Coloplast B: Stocks/Bonds|Express Scripts: Stocks/Bonds|Novo Nordisk A/S Spons ADR: Stocks/Bonds|Novo Nordisk A/S-B: Stocks/Bonds|Steris PLC: Stocks/Bonds|Stryker Corp: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds Geoffrey A. Weinberg, MD, Merck & Co.: Honoraria|Merck & Co.: Honoraria for composing and reviewing textbook chapters, Merck Manual of Therapeutics Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

Background Children can present with overlapping symptoms of acute respiratory illness (ARI) and acute gastroenteritis (AGE). In these cases, it is unclear if the etiologic agent is a respiratory pathogen, gastrointestinal pathogen, or both. Methods We analyzed data collected in Nashville, TN (12/01/2016–2/28/2020) as part of the New Vaccine Surveillance Network, a prospective ARI/AGE surveillance study. Children (< 18 years old) who presented to the emergency department or were admitted with fever and/or respiratory symptoms for < 14 days were enrolled as ARI subjects and had mid-turbinate nasal ± throat swabs collected, while children with ≥1 episode of vomiting and/or ≥3 episodes of diarrhea in 24 hours were enrolled as AGE subjects and had stool collected. Children who met both sets of criteria were dually enrolled. Respiratory specimens were tested for common respiratory viruses by molecular testing and stool specimens were tested for common gastrointestinal (GI) pathogens by Luminex GI Pathogen Panel. We compared detection groups using Pearson’s χ2 test. C. difficile detection in children < 2 years old was considered asymptomatic carriage (n=32). Results We identified 501 dual enrollees, among whom 279 (55.7%) had both a respiratory and stool specimen tested. Overall, 127 (45.5%) had only a respiratory virus detected, 33 (11.8%) had only a GI pathogen detected, 39 (14.0%) had both, and 77 (27.6%) had no detection (Table 1). Vomiting and diarrhea were frequently reported ( >50%) in all dual enrollees whether or not a pathogen was detected (Figure 1). Cough was detected in high frequency in all groups with pathogen detection. Children with respiratory-only or dual detection had a higher frequency of wheezing and shortness of breath than those with GI-only or no detection. The distribution of pathogens did not significantly differ between single and co-detected cases (Figure 2). Table 1Demographic characteristics of N=279* children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status.Figure 1Distribution of signs and symptoms in N=279 children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status. p values represent omnibus comparisons of all four groups.Figure 2Distribution of pathogens detected in N=279 children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status. Conclusion Children presenting with overlapping symptoms of ARI and AGE were more likely to have an ARI-associated virus. Lower respiratory symptoms (namely, wheezing and shortness of breath) were more specific for ARI-associated viral detection compared with other signs and symptoms. Disclosures Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.