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Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities.This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression.We compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28).In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.

BackgroundCommunity-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce.MethodsWe evaluated children and adolescents aged ResultsOf the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01–1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05–1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36–2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15–4.62]) was associated with bacterial coinfection.ConclusionsCommunity-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.

Previous studies of severe acute respiratory syndrome coronavirus 2 infection in infants have incompletely characterized factors associated with severe illness or focused on infants born to mothers with coronavirus disease 2019 (COVID-19). Here we highlight demographics, clinical characteristics and laboratory values that differ between infants with and without severe acute COVID-19.Active surveillance was performed by the Overcoming COVID-19 network to identify children and adolescents with severe acute respiratory syndrome coronavirus 2-related illness hospitalized at 62 sites in 31 states from March 15 to December 27, 2020. We analyzed patients7 days to1 year old hospitalized with symptomatic acute COVID-19.We report 232 infants7 days to1 year of age hospitalized with acute symptomatic COVID-19 from 37 US hospitals in our cohort from March 15 to December 27, 2020. Among 630 cases of severe COVID-19 in patients7 days to18 years old, 128 (20.3%) were infants. In infants with severe illness from the entire study period, the median age was 2 months, 66% were from racial and ethnic minority groups, 66% were previously healthy, 73% had respiratory complications, 13% received mechanical ventilation and1% died.Infants accounted for over a fifth of children18 years of age hospitalized for severe acute COVID-19, commonly manifesting with respiratory symptoms and complications. Although most infants hospitalized with COVID-19 did not suffer significant complications, longer term outcomes remain unclear. Notably, 75% of infants with severe disease were6 months of age in this cohort study period, which predated maternal COVID-19 vaccination, underscoring the importance of maternal vaccination for COVID-19 in protecting the mother and infant.

Background As of 2017 (WHO, 2017), diarrheal disease ranked second as a cause of worldwide mortality for children under five years of age. Approximately 50-70% of acute gastroenteritis (AGE) is viral in etiology, with commonly detected viruses including norovirus, rotavirus, and adenovirus. However, the epidemiology of less commonly detected viruses, specifically enterovirus (EV) and parechovirus A (PeV-A), associated AGE in the United States is not well described. The purpose of our study was to determine the prevalence of EV and PeV-A in children with AGE vs. healthy controls (HC) over a 7-year period. Methods From December 2011 – November 2018, we screened stool samples from children less than 18 years of age prospectively enrolled in Children’s Mercy-Kansas City’s (CM-KC) site for the CDC’s New Vaccine Surveillance Network; 3005 samples from subjects presenting with AGE and 1097 from HC. Samples from 2011 – 2016 (AGE: 2453; HC:752) and 2017 – 2018 (AGE:552; HC:344) were tested at CDC and CM-KC respectively by a real-time-PCR assay using specific EV and PeV-A primers targeting the highly conserved 5’ untranslated region. Demographic data were collected from EMR. Results Among 3005 AGE samples, EV was detected in 12.5% (n=386/3004), and PeV-A in 10.3% (n=252/3005). Among 1097 HC samples, EV was detected in 9.0% (99/1096), and PeV-A in 11.9% (130/1097). In 2014-2015 EV detection in AGE was highest (17.9%) among all years and significantly higher (p=0.004) than in HC samples (9.1%), whereas PeV-A detection in AGE was 9.5% vs. 15.6% in HC samples, p=0.008 (Table 1). Co-infections with EV and PeV-A were seen in 55 AGE and 21 HC. Most EV detections (45.1%) were in 1- to 2-year-olds, whereas PeV-A detections (47.3%) were in children < 1 year old (Table 2). Both EV (58.3%) and PeV-A (48.4%) detections were significantly more frequent in male children (p=0.006). The highest frequency of EV detections was in summer to fall months, and for PeV-A in late summer through early winter. Conclusion We report a higher prevalence of EV infections in AGE, and PeV-A infections in HC during 2011 to 2018, plus their seasonal and age distributions. Although our data do not currently demonstrate an association between detection of EV or PeV-A types and AGE, additional data could provide more clarity into a potential association. Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support 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 Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background Mycoplasma pneumoniae (MP), a common pediatric pneumonia pathogen, has 2 subtypes based on P1 adhesin gene variation. Macrolide-resistant MP (MRMP), seen since 2000 in many countries, has been subtype associated. Limited U.S. pediatric data exist on MP subtype or MRMP frequency and their clinical importance. Methods During 2015–2020, mid-turbinate nasal swab (MTNS) specimens and/or throat swabs were collected from children with acute respiratory illness (ARI) enrolled in emergency department (ED) or outpatient and inpatient settings at 4 CDC-funded New Vaccine Surveillance Network sites (Cincinnati, Seattle, Houston, and Kansas City). Specimens were tested for MP and common respiratory viruses by singleplex or multiplex polymerase chain reaction assay (PCR). P1-subtyping for MP positive specimens used multiplex TaqMan real-time PCR while MR was assessed by real time PCR with melt curve analysis (Lightmix®, TIBMolbiol). Select demographic/clinical data were analyzed by P1 subtype (P1–1 vs. P1–2). Results Of 208 MTNS specimens from 208 children (median age 5.5 years), 110 (53%) were P1–1, 89 (43%) P1–2, and 9 (4%) untypeable. Of 199 typeable specimens, 111 (56%) came from inpatients while 88 (44%) came from ED/outpatients.Overall MRMP prevalence during 2015–2020 was low (3/208,1.4%); all MRMP (Houston: 1 each in 2016–2017 and 2019–2020, Seattle: 1 in 2018–2019) were P1–1. Differences in P1–2 vs. P1–1 proportions were significant in 2 years: P1–2 dominated in 2015–2016; P1-1 in 2019–2020 (Figure 1). Common clinical symptoms for 199 MP-positive patients were fever (84%, mean 102.5±1.5oF), shortness of breath (82%), wheezing (67%), and cough (60%). Clinical manifestations, hospitalization, and antibiotic use did not differ in P1-1 vs. P1-2 patients. Antibiotics were used in 59/199 (30%) patients overall; amoxicillin was most frequent (48/199, 24%), followed by cefdinir (9/199, 5%) and azithromycin (5/199, 3%). Conclusion MP subtypes co-circulated during 2015–2020; P1-2 dominated in 2015–2016, P1-1 in 2018–2019. Signs/symptoms were similar for P1-1 and P1-2. MRMP detection was uncommon among our pediatric subjects. Ongoing surveillance is important to assess potential changes in MR prevalence and temporal subtype variation. Disclosures Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: 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 Janet A. Englund, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccine: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|SanofiPasteur: Advisor/Consultant.

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 According to the 2018 Infectious Diseases Society of America (IDSA) clinical practice guidelines and Centers for Disease Control and Prevention (CDC) guidance, clinicians should start antiviral treatment as soon as possible for children who are hospitalized with suspected or confirmed influenza. We assessed the use of influenza-specific antiviral therapy in children hospitalized with symptoms of acute respiratory illness and laboratory-confirmed influenza. Methods We conducted active, population-based surveillance of children hospitalized with fever and/or respiratory symptoms (12/01/2016–02/28/2020) at the seven U.S. medical centers that comprise the CDC New Vaccine Surveillance Network. We excluded children who did not undergo clinical testing (by rapid antigen testing or nucleic acid amplification test [NAAT]) or research testing (by NAAT) for influenza, those who presented out of influenza season (site- and season-specific), and those whose date of antiviral therapy or whether antiviral therapy was given was unknown. We assessed the use of influenza-specific antiviral therapy in this cohort and defined timely antiviral therapy as administration within 2 days of hospitalization. Results Of 11,275 eligible children, 1,149 (10.2%) tested positive for influenza by clinical and/or research assays (Table 1). Overall, 154 influenza cases (13.4%) were detected by clinical testing only, 428 (37.2%) by research testing only, and 567 (49.3%) by both. During their influenza-associated hospitalization, 620 children (54.0%) received influenza-specific antivirals, and therapy was timely in 572 cases (92.3%). Of those who tested positive clinically, 445/721 (61.7%) received timely antiviral therapy, 38 (5.3%) received delayed antiviral therapy, and 238 (33.0%) received no antiviral therapy. Oseltamivir was the antiviral used in all treated cases. The distribution of antiviral-treated cases varied by race and Hispanic origin and study site, but not by age at presentation or influenza season (Figure 1). Table 1 Demographic characteristics of 1,149 children with influenza enrolled in the New Vaccine Surveillance Network over four influenza seasons between December 1, 2016, and February 28, 2020. Figure 1Proportions of children with influenza enrolled in the New Vaccine Surveillance Network who received timely, delayed, or no antiviral therapy by age at presentation, race and Hispanic origin, study site, and influenza season (N=1,149). Conclusion Although antiviral therapy is recommended for all influenza-associated hospitalizations in children, antiviral prescribing remains suboptimal. Further studies would help identify and address barriers to antiviral therapy in children with influenza. Disclosures John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant 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 Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support 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 Geoffrey A. Weinberg, MD, Merck & Co.: Honoraria|Merck & Co.: Honoraria for composing and reviewing textbook chapters, Merck Manual of Therapeutics Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening testing is a recommended mitigation strategy for schools, although few descriptions of program implementation are available.MethodsKindergarten through 12th grade (K–12) students and staff practicing universal masking during the delta and omicron variant waves from five schools in Durham, North Carolina and eight schools in Kansas City, Missouri participated; Durham’s program was structured as a public health initiative facilitated by school staff, and Kansas City’s as a research study facilitated by a research team. Tests included school-based rapid antigen or polymerase chain reaction testing, at-home rapid antigen testing, and off-site nucleic acid amplification testing.ResultsWe performed nearly 5700 screening tests on more than 1600 K–12 school students and staff members. The total cost for the Durham testing program in 5 public charter K–12 schools, each with 500–1000 students, was $246 587 and approximately 752 h per semester; cost per test was $70 and cost per positive result was $7076. The total cost for the Kansas City program in eight public K–12 schools was $292 591 and required approximately 537 h in personnel time for school-based testing; cost per test was $132 and cost per positive result was $4818. SARS-CoV-2 positivity rates were generally lower (0–16.16%) than rates in the community (2.7–36.47%) throughout all testing weeks.Conclusions and RelevanceVoluntary screening testing programs in K–12 schools are costly and rarely detect asymptomatic positive persons, particularly in universally masked settings.Clinical Trial RegistrationNCT04831866.

Background Pfizer-BioNTech COVID-19 vaccine received emergency use authorization for persons ≥ 16 years in December 2020 and for adolescents 12–15 years in May 2021. Despite the clear benefits and favorable safety profile, vaccine uptake in adolescents has been suboptimal. We sought to assess factors associated with COVID-19 non-vaccination in adolescents 12–18 years of age. Methods Between June 1, 2021 and April 29, 2022, we assessed factors associated with COVID-19 non-vaccination in hospitalized adolescents ages 12–18 years enrolled in the Overcoming COVID-19 vaccine effectiveness network. Demographic characteristics and clinical information were captured through parent interviews and/or electronic medical record abstraction; COVID-19 vaccination was assessed through documented sources. We assessed associations between receipt of the COVID-19 vaccine and demographic and clinical factors using univariate and multivariable logistic regression and estimated adjusted odds ratios (aOR) for each factor associated with non-vaccination. Results Among 1665 hospitalized adolescents without COVID-19, 56% were unvaccinated. Unvaccinated adolescents were younger (median age 15.1 years vs. 15.4 years, p Conclusions Efforts to increase COVID-19 vaccination of adolescents should focus on persons with geographic, socioeconomic, and medical risk factors associated with non-vaccination.

Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.

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.

Background Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood has high sensitivity in adults with acute coronavirus disease 2019 (COVID-19), but sensitivity in pediatric patients is unclear. Recent data suggest that persistent SARS-CoV-2 spike antigenemia may contribute to multisystem inflammatory syndrome in children (MIS-C). We quantified SARS-CoV-2 nucleocapsid (N) and spike (S) antigens in blood of pediatric patients with either acute COVID-19 or MIS-C using ultrasensitive immunoassays (Meso Scale Discovery). Methods Plasma was collected from inpatients ( Results Specificities of N and S assays were 95–97% and 100%, respectively. In acute COVID-19 patients, N/S plasma assays had 89%/64% sensitivity; sensitivities in patients with concurrent nasopharyngeal swab cycle threshold (Ct) ≤35 were 93%/63%. Antigen concentrations ranged from 1.28–3844 pg/mL (N) and 1.65–1071 pg/mL (S) and correlated with disease severity. In MIS-C, antigens were detected in 3/53 (5.7%) samples (3 N-positive: 1.7, 1.9, 121.1 pg/mL; 1 S-positive: 2.3 pg/mL); the patient with highest N had positive nasopharyngeal RT-PCR (Ct 22.3) concurrent with blood draw. Conclusions Ultrasensitive blood SARS-CoV-2 antigen measurement has high diagnostic yield in children with acute COVID-19. Antigens were undetectable in most MIS-C patients, suggesting that persistent antigenemia is not a common contributor to MIS-C pathogenesis.

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 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.

Background It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. Methods Between March 15, 2020 and December 27, 2020, children, No therapies for acute coronavirus disease 2019 (COVID-19) have been tested in children to establish effectiveness. Despite this, across 48 hospitals, 235/424 children (55%) admitted to the intensive care or step-down unit with COVID-19 received directed therapies. Systemic steroids and remdesivir were most commonly administered, with use rising from March 2020 to December 2020.

Pediatric saliva specimen demonstrated high sensitivity (93%) and specificity (96.2%) compared to paired nasopharyngeal swabs (NPS) by Aptima SARS-CoV-2 Assay (Aptima). Viral loads were comparable in both specimen types. Saliva is a safe, noninvasive, and acceptable alternative specimen for SARS-CoV-2 detection in children.

Respiratory viral infections are a leading cause of pediatric disease. Emerging respiratory viruses can cause outbreaks with significant morbidity and mortality or circulate routinely. The rapid identification of pathogens, epidemiologic tracing, description of symptoms, and development of preventative and therapeutic measures are crucial to limiting the spread of these viruses. Some emerging viruses, such as rhinovirus C and influenza C, circulate yearly but were previously undetected due to limited diagnostic methods. Although some pathogens have a geographic focus, globalization dictates that providers be aware of all emerging diseases in order to recognize outbreaks and diagnose and treat patients.

Background Sharp declines in influenza and respiratory syncytial virus (RSV) circulation across the U.S. have been described during the pandemic in temporal association with community mitigation for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine relative frequencies of rhinovirus/enterovirus (RV/EV) and other respiratory viruses in children presenting to emergency departments or hospitalized with acute respiratory illness (ARI) prior to and during the COVID-19 pandemic. Methods We conducted a multi-center active prospective ARI surveillance study in children as part of the New Vaccine Surveillance Network (NVSN) from December 2016 through January 2021. Molecular testing for RV/EV, RSV, influenza, and other respiratory viruses [i.e., human metapneumovirus, parainfluenza virus (Types 1-4), and adenovirus] were performed on specimens collected from children enrolled children. Cumulative percent positivity of each virus type during March 2020–January 2021 was compared from March-January in the prior seasons (2017-2018, 2018-2019, 2019-2020) using Pearson’s chi-squared. Data are provisional. Results Among 69,403 eligible children, 37,676 (54%) were enrolled and tested for respiratory viruses. The number of both eligible and enrolled children declined in early 2020 (Figure 1), but 4,691 children (52% of eligible) were enrolled and tested during March 2020-January 2021. From March 2020-January 2021, the overall percentage of enrolled children with respiratory testing who had detectable RV/EV was similar compared to the same time period in 2017-2018 and 2019-2020 (Figure 1, Table 1). In contrast, the percent positivity of RSV, influenza, and other respiratory viruses combined declined compared to prior years, (p< 0.001, Figure 1, Table 1). Figure 1. Percentage of Viral Detection Among Enrolled Children Who Received Respiratory Testing, New Vaccine Surveillance Network (NVSN), United States, December 2016 – January 2021 Table 1. Percent of Respiratory Viruses Circulating in March 2020– January 2021, compared to March-January in Prior Years, New Vaccine Surveillance Network (NVSN), United States, March 2017 – January 2021 Conclusion During 2020, RV/EV continued to circulate among children receiving care for ARI despite abrupt declines in other respiratory viruses within this population. These findings warrant further studies to understand virologic, behavioral, biological, and/or environmental factors associated with this continued RV/EV circulation. Disclosures Jennifer E. Schuster, MD, Merck, Sharpe, and Dohme (Individual(s) Involved: Self): Grant/Research Support Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Claire Midgley, PhD, Nothing to disclose Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support

Background Influenza C virus (ICV) is associated with acute respiratory infection (ARI); however, the burden of ICV is not well-described. We sought to determine the burden and characteristics of ICV in a prospective, population-based cohort. Methods The study was conducted within the New Vaccine Surveillance Network (NVSN), a CDC-led, seven-site network that performs population-based surveillance for ARI in children < 5 years. Nasal/throat swabs were collected from emergency department (ED) or inpatient children with ARI, or healthy controls in clinic, between 12/05/2016-10/31/2019 and tested by real-time RT-PCR for ICV and other respiratory viruses. Preliminary data were extracted and demographic/clinical features of ICV+ cases analyzed. We sequenced the hemagglutinin-esterase (HE) gene from ICV+ Pittsburgh samples. Results Among 19,321 children with ARI or healthy controls enrolled and tested for ICV from 2016-2019, 115/17,668 (0.7%) ARI cases and 8/1653 (0.5%) healthy controls tested positive for ICV. The median age of ICV+ ARI subjects was 19 months (IQR 10,46) and 81(70%) were ≤36 months. 42.6% (49) were white, 33.9% (39) black, and 16.5% (19) Hispanic, with the remainder Asian or unknown; 56.5% (62) attended daycare. Among ICV+ ARI cases, 67.8% (78) had fever, 94.8% (109) cough, and 60.8% (70) wheezing. 45.2% (52) ICV+ cases occurred in 2016-17, 6.5% (8) in 2017-2018, and 47.8% (55) in 2018-19 (Table). 40% (46) of ICV+ cases were seen in the ED, while the remainder were inpatients. Median length of stay was 2d (IQR,1-3) with 15 admitted to ICU. 67.8% (78/115) ARI cases had 1 or 2 co-detected pathogens, with rhinovirus (26), respiratory syncytial virus (26), and adenovirus (14) most frequently co-detected. ARI symptoms including fever, myalgias, chills, and wheezing did not differ significantly between coinfected subjects and those who were only ICV+. HE sequences were in the two currently circulating Kanagawa and Sao Paulo lineages. ICV+ Cases by Site and Year Conclusion ICV was an uncommon cause of ARI symptoms leading to healthcare encounters in young children. The prevalence varied year-to-year and between different geographic regions. Most children infected with ICV were ≤3 years old and had co-detected pathogens. ICV was similarly rarely detected in healthy controls. Disclosures Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member)

Background The 2019–20 influenza season was predominated by early onset B/Victoria viruses followed by A(H1N1)pdm09 virus circulation. Over 95% of circulating B/Victoria viruses were subclade V1A.3, different from the Northern Hemisphere vaccine strain. Annual estimates of influenza vaccine effectiveness (VE) are important because of frequent changes in circulating and vaccine viruses. Methods We assessed VE among children 6 months–17 years old with acute respiratory illness and Results Among 2022 inpatients, 324 (16%) were influenza positive: 38% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone (Table). Among 2066 ED children, 653 (32%) were influenza positive: 45% with influenza B/Victoria alone and 43% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval [CI], 51%–70%) against any influenza-related hospitalizations, 68% (95% CI, 55%–78%) for A(H1N1)pdm09 and 55% (95% CI, 35%–69%) for B/Victoria. VE by age group for any influenza-related hospitalizations was 57% (95% CI, 40%–69%) among children 6 months to < 5 years and 66% (95% CI, 49%–77%) among children 5–17 years. VE was 53% (95% CI, 42%–62%) against any influenza-related ED visits, 46% (95% CI, 28%–60%) for A(H1N1)pdm09 and 54% (95% CI, 39%–66%) for B/Victoria. VE by age group was 52% (95% CI, 37%–63%) among children 6 months to < 5 years and 42% (95% CI, 16%–60%) among children 5–17 years. Conclusion Influenza vaccination in the 2019–20 season provided substantial protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the two predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus V1A.3 subclade. Disclosures Janet A. Englund, MD, AstraZeneca (Scientific Research Study Investigator)GSK group of companies (Scientific Research Study Investigator)Meissa vaccines (Consultant)Merck (Scientific Research Study Investigator)Sanofi Pasteur (Consultant) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support) Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial)

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts, meets 3 times per year to develop recommendations for vaccine use in the United States. The group has 15 voting members, and each member's term is 4 years. ACIP members and Centers for Disease Control and Prevention (CDC) staff discuss the epidemiology of vaccine-preventable diseases and vaccine research, effectiveness, safety data, and clinical trial results. Representatives from the American Academy of Pediatrics (C. L. B. and Y. A. M.) and the Pediatric Infectious Diseases Society (S. T. O.) are present as liaisons to the ACIP. The ACIP met February 22 and 23, 2017, to discuss proposed recommendations regarding vaccination for unprotected infants born to hepatitis B surface antigen (HBsAg)-positive mothers; topics included cost analysis, influenza surveillance, influenza vaccine effectiveness, herpes zoster vaccine, and considerations for meningococcal serogroup B booster doses in groups at increased risk. Updates on mumps epidemiology, Dengue virus vaccines, Zika virus vaccines, adult immunization, and yellow fever vaccine were also provided.

Background Acute gastroenteritis (AGE) in hematopoietic cell transplant (HCT) patients causes significant morbidity and mortality. Data regarding the longitudinal assessment of infectious pathogens during symptomatic AGE and asymptomatic periods, particularly in children, are limited. We investigated the prevalence of AGE-associated infectious pathogens in children undergoing allogeneic HCT. Methods From March 2015 through May 2016, 31 pediatric patients at 4 US children’s hospitals were enrolled and had stool collected weekly from pre-HCT through 100 days post-HCT for infectious AGE pathogens by molecular testing. Demographics, clinical symptoms, antimicrobials, vaccination history, and outcomes were manually abstracted from the medical record into a standardized case report form. Results We identified a pathogen in 18% (38/206) of samples, with many detections occurring during asymptomatic periods. Clostridioides difficile was the most commonly detected pathogen in 39% (15/38) of positive specimens, although only 20% (3/15) of C. difficile–positive specimens were obtained from children with diarrhea. Detection of sapovirus, in 21% (8/38) of pathogen-positive specimens, was commonly associated with AGE, with 87.5% of specimens obtained during symptomatic periods. Norovirus was not detected, and rotavirus was detected infrequently. Prolonged shedding of infectious pathogens was rare. Conclusions This multicenter, prospective, longitudinal study suggests that the epidemiology of AGE pathogens identified from allogeneic HCT patients may be changing. Previously reported viruses, such as rotavirus and norovirus, may be less common due to widespread vaccination and institution of infection control precautions, and emerging viruses such as sapoviruses may be increasingly recognized due to the use of molecular diagnostics.

Kawasaki disease (KD) shock syndrome (KDSS) is hypotension with KD. We compared children with KDSS and matched control children with KD. Children with KDSS more often were female, had a lower platelet count and sodium concentration, had a condition refractory to immunoglobulin, and had abnormal echocardiography results. KDSS is a unique subset of KD.

Background Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics. Methods We conducted a retrospective study covering 2005–2014 at 5 pediatric centers in 3 U.S. regions. Possible AFM cases aged ≤18 years were identified by searching discharge ICD-9 codes and spinal cord MRI reports (>37,000). Neuroradiologists assessed MR images, and medical charts were reviewed; possible cases were classified as AFM, not AFM, or indeterminate. Results At 5 sites combined, 26 AFM cases were identified from 2005–2013 (average annual number, 3 [2.4 cases/100,000 pediatric hospitalizations]) and 18 from 2014 (12.6 cases/100,000 hospitalizations; Poisson exact p

Background Pediatric hematopoietic cell transplant (HCT) recipients often fail to have robust responses to influenza (flu) vaccine. We conducted a blinded phase II trial comparing high-dose (HD) trivalent inactivated vaccine (TIV) vs. standard dose (SD) quadrivalent inactivated vaccine (QIV). Methods Children 3–17 years old and 3–35 months post-allogeneic HCT were enrolled at 9 centers and randomized to either 2 doses of HD-TIV or SD-QIV during the 2016–2017 flu season. We compared immune responses by hemagglutination inhibition (HAI) from children 3–11 (early) vs. 12–35 (late) months (m) post-HCT to 3 common flu vaccine antigens, irrespective of vaccine type. HAI responses were evaluated at baseline (visit 1), 1 m post dose 1 (visit 2) and dose 2 (visit 3), and 7 m post dose 2 (visit 4). Geometric mean titers (GMT) were adjusted for baseline log-titer values. Results Thirty-one children, median age 11 (7–15) years, were enrolled; 17 (55%) were immunized early and 14 (45%) late. Over 50% of patients had a potentially seroprotective (≥1:40) HAI titer at baseline, with no significant difference post-vaccination between early and late subjects. Table 1 compares early vs late subjects with HAI seroconversion (4-fold HAI titer rise). Post dose 1, late subjects, compared with early, had higher rates of seroconversion to all influenza strains. Post dose 2, early subjects, compared with late, had increased seroconversion. Late subjects had higher GMTs for H1N1 post dose 1 and 2, H3N2 after dose 1, and strain B/VIC post dose 1 and 2 (Figure 1). Although immunogenicity waned throughout flu season, higher seroconversion rates and GMT to H3N2 and strain B/VIC were retained in late subjects. Conclusion Compared with subjects in early post-HCT group, late post-HCT subjects had better flu vaccine immune responses as noted by higher GMT and HAI seroconversion. However, 2 doses seemed more beneficial in the early post-HCT group. Future analyses are underway, including comparing immunogenicity of HD vs. SD flu vaccine. Disclosures Jennifer E. Schuster, MD, Satchel Health: Shareholder Flor M. Munoz, M.D, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.

BACKGROUND Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection in young children. Our objectives were to define HMPV epidemiology and circulating strains and determine markers of severe disease in Jordanian children. METHODS We conducted a prospective study from March 16, 2010 to March 31, 2013 using quantitative reverse transcription-polymerase chain reaction to determine the frequency of HMPV infection among children

Background Enterovirus 68 (EV-D68) causes acute respiratory tract illness in epidemic cycles, most recently in Fall 2014, but clinical characteristics of severe disease are not well reported. Objectives Children with EV-D68 severe respiratory disease requiring pediatric intensive care unit (PICU) management were compared with children with severe respiratory disease from other enteroviruses/rhinoviruses. Study design A retrospective review was performed of all children admitted to Children’s Mercy Hospital PICU from August 1-September 15, 2014 with positive PCR testing for enterovirus/rhinovirus. Specimens were subsequently tested for the presence of EV-D68. We evaluated baseline characteristics, symptomatology, lab values, therapeutics, and outcomes of children with EV-D68 viral infection compared with enterovirus/rhinovirus-positive, EV-D68-negative children. Results A total of 86 children with positive enterovirus/rhinovirus testing associated with respiratory symptoms were admitted to the PICU. Children with EV-D68 were older than their EV-D68-negative counterparts (7.1 vs. 3.5 years, P = 0.01). They were more likely to have a history of asthma or recurrent wheeze (68% vs. 42%, P = 0.03) and to present with cough (90% vs. 63%, P = 0.009). EV-D68 children were significantly more likely to receive albuterol (95% vs. 79%, P = 0.04), magnesium (75% vs. 42%, P = 0.004), and aminophylline (25% vs. 4%, P = 0.03). Other adjunctive medications used in EV-D68 children included corticosteroids, epinephrine, and heliox; 44% of EV-D68-positive children required non-invasive ventilatory support. Conclusions EV-D68 causes severe disease in the pediatric population, particularly in children with asthma and recurrent wheeze; children may require multiple adjunctive respiratory therapies.

BACKGROUND Enterovirus D68 (EV-D68) has been sporadically reported as a cause of respiratory tract infections. In 2014, an international outbreak of EV-D68 occurred and caused severe respiratory disease in the pediatric population. METHODS A retrospective chart review was performed of children admitted to Children's Mercy Hospital from August 1, 2014, to September 15, 2014, with positive multiplex polymerase chain reaction testing for EV/rhinovirus (RV). Specimens were subsequently tested for EV-D68, and clinical data were obtained from the medical records. Patients with EV-D68 were compared with children presenting simultaneously with other EV/RV. RESULTS Of 542 eligible specimens, children with EV-D68 were significantly older than children with other EV/RV (4.6 vs. 2.2 years, P < 0.001). Children with EV-D68 were more likely to have a history of asthma (38.6% vs. 30.0%, P = 0.04) or recurrent wheezing (22.1% vs. 14.8%, P = 0.04). EV-D68-positive children more commonly received supplemental oxygen (86.7% vs. 65.0%, P < 0.001), albuterol (91.2% vs. 65.5%, P < 0.001) and corticosteroids (82.9% vs. 58.6%, P < 0.001). Age ≥5 years was an independent risk factor for intensive care unit management in EV-D68-infected children. Children with a history of asthma or recurrent wheezing and EV-D68 received supplemental oxygen (92.7% vs. 82.4%, P = 0.007) and magnesium (42.7% vs. 29.7%, P = 0.03) at higher rates and more continuous albuterol (3 vs. 2 hours, P = 0.03) than those with other EV/RV. CONCLUSIONS EV-D68 causes severe disease in the pediatric population, particularly in children with a history of asthma or recurrent wheezing. EV-D68-positive children are more likely to require therapy for refractory bronchospasm and may need intensive care unit- level care.

Background Acute gastroenteritis (AGE) is a frequent sequela in children undergoing hematopoietic cell transplant (HCT). Although rotavirus and norovirus have been implicated as important causes of AGE, the frequency of other pathogens is unknown. Little data exist on longitudinal prevalence of infectious AGE in HCT. Methods From February 2015 to May 2016, subjects Results Thirty-one patients were enrolled at four sites (Seattle: 13, Kansas City: 8, Oakland: 6, Nashville: (4) with median age 5 (IQR 3–10) years. Two hundred sixteen samples were obtained with median 7 samples/subject. During the first 100 days, 29 (94%) subjects met the AGE definition. Thirty-six single pathogen detections occurred in 16 (52%) subjects. Clostridium difficile was the most frequent pathogen (Figure 1), with 14 detections in nine patients, all ≥3 years; 50% of detections were asymptomatic. Seven (50%) detections occurred at HCT onset and none received targeted C. difficile therapy. Sapovirus was detected nine times in four patients, with seven (78%) detections associated with AGE symptoms. Rotavirus was detected nine times, during five symptomatic episodes, in three patients. Adenovirus was detected four times in three patients and all were symptomatic. Conclusion We longitudinally characterized the etiology of infectious AGE in children undergoing HCT. Despite the majority of patients meeting the definition for AGE, only half had a pathogen detected, suggesting that differentiating infectious vs. noninfectious AGE (e.g., medication induced) in this population is difficult. Although all subjects with adenovirus and most with sapovirus were symptomatic, asymptomatic C. difficile detection was common. Interestingly, norovirus was not detected. Further investigation of AGE is warranted in this population. Disclosures All authors: No reported disclosures.

Background Hematopoietic cell transplant (HCT) recipients are at a significantly greater risk for invasive pneumococcal disease than the general population. However, pneumococcal colonization in pediatric HCT recipients has not been widely studied. We evaluated the dynamics of pneumococcal colonization in pediatric patients undergoing HSCT from conditioning regimen to 100 days post HCT. Methods Mid-turbinate samples obtained from pediatric patients undergoing HCT at Children’s Mercy from September 2015 to January 2017 were tested for Streptococcus pneumoniae colonization via real-time PCR using lytA primer (autolysin-A-encoding gene). A cycle threshold value ≤35 was considered positive. First sample was obtained during conditioning regimen (week 1), second sample after HCT (week 2). Then, weekly samples were obtained for the first 100 days after HSCT. Results Twenty-two patients were included, representing 266 mid-turbinate samples. The median age at the time of HSCT was 9.5 years (IQR 3–16), and 14 patients were male (63.6%). The indication for HSCT was oncologic (15, 68.2%), hematologic (5, 22.7%) and immune deficiency (2, 9.1%). Fourteen patients (63.6%) underwent allogenic HSCT. Six patients had documentation in our electronic medical record system of receiving ≥ 1 pneumococcal conjugate vaccine prior to conditioning regimen. Nine (40.9%) of 22 patients were colonized with S. pneumoniae, their median age was 14 years (IQR 2.5–16). Pneumococcal colonization during conditioning regimen was 9% (2/22). Pneumococcal colonization from week 14 to week 16 was 42% (5/12). Conclusion A third of pediatric HCT recipients were colonized with S. pneumoniae. Pneumococcal colonization was mainly identified either at the time of conditioning regimen or toward the end of the first 100 days after HCT, with the latter being the most common. Disclosures All authors: No reported disclosures.

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.

Children’s Mercy Hospital–Kansas City (CMH) sits on the border of 2 states and provides care to children from a 5-state region. On August 15, 2014, the CMH Division Director of Pediatric Infectious Diseases (ID) received an e-mail from a pediatric emergency department (ED) physician. This ED physician noted that in the previous 24 hours, she had seen 6 children who were disproportionately ill with respiratory distress; several of them required admission to the pediatric intensive care unit. The ED physician instinctively sensed that something was different about these children and asked her pediatric ID consultant for diagnostic assistance. Specifically, her e-mailed question to the consultant was, “Is there a ferocious lower respiratory virus in the community?”

On the basis of strong research evidence and consensus, (1) (2) (3) (4) human metapneumovirus is a leading cause of upper and lower respiratory tract infections in children. On the basis of research evidence and consensus, (3) (5) (6) (7) the clinical features of MPV-associated disease are similar to those of RSV. MPV is an important cause of asthma exacerbations, bronchiolitis, and pneumonia. Bacterial superinfection can occur.On the basis of research evidence and consensus, (2) (3) (8) the mean age of infection is 6 to 12 months, and nearly all school-age children are seropositive. However, infection can recur, likely in part due to impaired CD8+ T-cell response. On the basis of research evidence and consensus, (9) (10) (11) morbidity and mortality are the highest in patients who are premature, are immunosuppressed, or have underlying cardiopulmonary abnormalities. On the basis of research evidence and consensus, (2) commercially available diagnostic tests exist, and reverse transcriptase–PCR is the most commonly used. On the basis of consensus, because of a lack of relevant clinical studies, recombinant virus vaccines and monoclonal antibodies may be useful as prophylactics or therapeutics. (10)

Human metapneumovirus (HMPV), a paramyxovirus identified in 2001, is a leading cause of acute respiratory disease worldwide [1, 2]. In high-risk populations, HMPV causes significant morbidity and mortality [3, 4]. No vaccines or therapeutics specifically target HMPV, and nonspecific therapies such as ribavirin and intravenous immunoglobulin have limited efficacy [5]. HMPV has 4 subgroups, which vary in prevalence but cause similar disease [6, 7]. Although the subgroups are relatively conserved, recurrent infection occurs throughout life [8]. Reinfection likely occurs because of limited cross-protective antibodies [9] and T-cell exhaustion causing a poor memory response [10]. All paramyxoviruses have class I viral fusion (F) proteins, which exist in a pre- and postfusion state and are required for entry [11]. HMPV vaccine studies have focused on the F protein, which is immunogenic and protective in animal models [12, 13]. The F protein is highly conserved among HMPV subgroups, with >95% amino acid similarity between A and B groups and >97% similarity within a single group, suggesting that a broadly neutralizing antibody response could be evoked if a shared epitope were targeted [14]. Monoclonal antibodies (mAbs) are effective at preventing infectious diseases in high-risk populations [15]. However, the use of humanized or chimeric mAbs, both partly murine, is associated with the development of host antibodies to foreign antigens and adverse events [16, 17]. Fully human mAbs are less immunogenic [18]. Researchers have described mAbs effective at neutralizing all 4 subgroups of HMPV in vitro [19, 20], but these had limited therapeutic efficacy in rodents [21]. We hypothesized that a human mAb directed at HMPV F protein could be used to abate infection. Here, we describe a fully human mAb, 54G10, which potently neutralized all 4 subgroups of HMPV in vitro and exhibited subnanomolar affinity for the F protein. To test in vivo efficacy, we established a new mouse model permissive for all 4 HMPV subgroups in the upper and lower airways. 54G10 decreased peak HMPV titer below the limit of detection (LOD) in both prophylactic and therapeutic experiments. Sequencing of mAb-resistant mutants (MARMs) identified that 54G10's epitope is a conserved region among paramyxoviruses [22]. Confirming this, 54G10 neutralized respiratory syncytial virus (RSV), another leading cause of respiratory infections. Thus, 54G10 is a highly effective human mAb, which recognizes a similar epitope on HMPV and RSV.

Meningitis is an unusual clinical manifestation of Histoplasma capsulatum infection in nonimmunosuppressed children. We report a previously healthy 6-year-old boy with primary, chronic histoplasma meningitis and magnetic resonance imaging findings consistent with demyelinating disease presenting with brief, intermittent neurological manifestations for 7 months before diagnosis.