Antimicrobial resistance (AMR) continues to grow worldwide. For Staphylococcus aureus (S. aureus), antibiotic resistant phenotypes have expanded in community settings, especially for skin/soft tissue infections (SSTIs). Resistance to clindamycin and other non-beta lactam antibiotics leads to multidrug resistance (MDR)S. aureus.Association mining is an unsupervised machine learning algorithm that examines higher-order relationships between resistant antibiotics. It can quantify prevalence (support) and strength of association (lift). We apply artificial intelligence (AI) using AM to understand MDR S. aureus patterns in children with SSTIs over time. Data on children with SSTI seen in a large pediatric healthcare system in Atlanta, GA, U.S.A. were obtained retrospectively (2002-2019). Using AI, we applied association rule mining to look for antibiotic resistant patterns meeting the criteria: S. aureus SSTI from patients < 19 Y living in Atlanta. Association rule mining applied to identify antibiotic resistant phenotypes most frequent/clinically relevant (using Apriori algorithm), based on arules package in R. The following antibiotic classes were included in the analyses:clindamycin, erythromycin, gentamicin, linezolid, oxacillin, rifampin, trimethoprim-sulfamethoxazole, tetracycline, and vancomycin. Interestingness measures, including support (prevalence of resistance patterns) and lift (strength of associations between resistances) were employed to extract frequent and reliable patterns and then stratified by year and methicillin susceptibility. Analyses conducted in R. Preliminary analyses of subset (2002-2016) of data shows 40 distinct MDR S. aureus phenotypes from 8,171 children with SSTI. Clindamycin resistance was found in 19/40 (48%) phenotypes, 27/40 (68%) phenotypes had >3 resistant antibiotic classes, 11/40 (28%) occurred only in later years, and 4/40 (10%) had persistent phenotype through entire study period. Trends of MDRS. aureus are clustered around specific phenotypes. Association mining of S. aureus phenotypes across time can benefit antimicrobial stewardship programs by demonstrating which resistant patterns are circulating in the community setting. Lilly Immergluck, MD, MS, American Academy of Pediatrics: Board Member|Department of Energy: Grant/Research Support|moderna: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support

Background:Antibiograms monitor antibiotic resistance trends and help guide empiric antibiotic treatment. A statewide pediatric antibiogram can help inform stewardship efforts. Methods:Annual pediatric antibiograms for the five children's hospitals in Georgia from 2014-2023 were collected. All sites used the Clinical and Laboratory Standards Institute guidelines for antibiogram development. Antibiogram data were combined, and the most common bacteria were included: Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex and Pseudomonas aeruginosa. Interhospital differences were compared for methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), E. coli and K. pneumoniae. The combined data from 2014 and 2023 were compared to demonstrate antibiotic susceptibility changes over time. Results:Data in 2023 for MSSA and MRSA showed clindamycin susceptibility was 78% and 82%, respectively. S. pneumoniae susceptibility to amoxicillin/clavulanate was 96%. E. faecalis resistance to ampicillin and vancomycin was rare. For all included gram-negative bacteria, susceptibility remained high to 3rd generation cephalosporins (90%-92%) and meropenem (95%-99%). From 2014 to 2023, the rate of MRSA decreased from 49% to 33.5%. S. pneumoniae susceptibility to amoxicillin/clavulanate and clindamycin significantly increased. For E. coli, there was a significant decrease in susceptibility for cefazolin (90% to 84%), ceftriaxone (95% to 92%), and meropenem (100% to 99%). There were nonsignificant decreases in susceptibility for K. pneumoniae. Conclusion:Over the past 10 years, MRSA rates decreased, S. pneumoniae antibiotic susceptibility increased, and gram-negative bacilli susceptibility was stable to slightly decreased. Georgia antibiogram data support the recommended antibiotic treatment for common pediatric infections.

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by experts in both adult and pediatric laboratory and clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including arboviral Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also addressed. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Background: Evolving epidemiological data and increasing antibiotic resistance mandate an update of the European and North American Societies of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. Methods: Certainty of evidence and strength of recommendations were rated by experts according to the Grading of Recommendation Assessment, Development, and Evaluation approach. PICO (patient population, intervention, comparator, and outcome) questions were developed and voted on by the group. Recommendations were formulated using the Evidence to Decision framework. Results: The current literature supports many of the previous recommendations and several new recommendations. Invasive testing with strain antimicrobial susceptibility analysis is recommended for the diagnosis and selection of eradication therapy for H. pylori infection. Molecular methods are acceptable for detection of infection and of antibiotic resistance in gastric biopsy specimens. Reliable, noninvasive tests can be used as a screening method for children with history of gastric cancer in a first-degree relative. When investigating causes of chronic immune thrombocytopenic purpura, testing for H. pylori is no longer recommended. When investigating other diseases such as inflammatory bowel disease, celiac disease, or eosinophilic esophagitis, specific diagnostic biopsies for H. pylori infection are not indicated. However, if H. pylori is an incidental finding, treatment may be considered after discussing the risks and benefits. Treatment should be based on antibiotic antimicrobial susceptibility testing and, if unavailable, regimens containing clarithromycin should be avoided. Conclusions: Due to decreasing prevalence of infection, increasing challenges with antibiotic resistance, and emerging evidence regarding complications of infection, clinicians must be aware of these recommended changes to appropriately manage H. pylori infection and its clinical sequelae in children.

Background: Antibiograms are used to monitor antibiotic resistance trends and help guide empiric antibiotic treatment. Community pediatricians may not have access to or be comfortable using children’s hospital antibiograms. Creating and disseminating a statewide pediatric antibiogram can help inform antibiotic stewardship efforts.Objective: To develop a pediatric-specific antibiogram for the state of Georgia. Methods: Annual pediatric antibiograms for the 5 children’s hospitals in Georgia from 2014 through 2021 were collected. All sites complied with the Clinical and Laboratory Standards Institute guidelines for antibiomicrobic breakpoints and antibiogram development. Antibiogram data were combined, and the most common bacteria were selected to incorporate into the statewide antibiogram: Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Pseudomonas aeruginosa. Antibiogram data were reported as percentage susceptible and total number of isolates. Interhospital susceptibility differences were compared for methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), E. coli, and K. pneumoniae from 2018 through 2021. P < .05 was considered significant. The combined antibiogram data from 2014 through 2021 were used to show antibiotic susceptibility trends over time. Results: The 2021 antibiogram is shown in the Table. For MSSA and MRSA, clindamycin susceptibility was 80% and 85%, respectively. K. pneumoniae susceptibility to amoxicillin-clavulanate was 91%. For E. coli, using urine-specific breakpoints, susceptibility to cefazolin was 89%. A few statistically significant differences in antibiotic susceptibility were detected between hospitals, but most were unlikely to be clinically relevant (all susceptibilities ≥90% or < 80%). A notable exception was trimethoprim-sulfamethoxazole susceptibility for K. pneumoniae, which ranged from 74% to 98% in 2020 and from 74% to 86% in 2021. From 2014 to 2021, the percentage of MRSA decreased from 49% to 34%. Over the 8 years, susceptibility to ceftriaxone for E. coli ranged from 93% to 95% and from 90% to 95% for K. pneumoniae. Susceptibility to meropenem for E. coli and K. pneumoniae ranged from 99% to 100%. Conclusions: Antibiotic susceptibility for pediatric bacterial isolates in Georgia remained stable over time and supported the narrow-spectrum empiric antibiotic treatment recommended in national evidence-based guidelines for skin and soft-tissue infections, community-acquired pneumonia, and uncomplicated urinary tract infections. MRSA rates decreased over time and multidrug-resistant gram-negative bacilli were uncommon and remained stable.Disclosures: None

Rapid Antigen Tests (RAT) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of eight commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR Cycle threshold (C T ) value (a proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using C T value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.

Abstract Background Staphylococcus aureus (S. aureus) is a common cause of skin and soft tissue infections (SSTIs). Both the β-lactam resistant form, methicillin resistant S. aureus (MRSA), and non-resistant form, methicillin susceptible S. aureus (MSSA) are associated with disparate infections across age and race; community-associated infections are often due to S. aureus US300. Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is a used in clinical microbiology laboratories to identify bacterial species, but limited data is available on if this tool can identify different strains of S. aureus. We hypothesize that MALDI-TOF MS can be used to identify strain-specific peaks of S. aureus USA300. Methods Children were enrolled from emergency departments and swabbed for S. aureus (anterior nares, axilla, perirectal, oropharyngeal, and wounds) during two time periods (2006-2008 and 2015-2016). MALDI-TOF MS was performed on S. aureus cultured from study participants. Default parameters used for variance stability, smoothing, baseline subtraction, and normalization in R 4.4.3. and MALDIquant v1.22 were applied to raw data. Peak detection and alignment were performed with a signal-to-noise ratio of three and tolerance of 300 ppm. Binning and machine learning algorithms were used to identify intensity differences of each peak identified; significance of peaks was determined using Chi Square statistical analyses, comparing MRSA and MSSA, and then between all S. aureus isolates compared to USA300. Statistical significance was considered with p-value < 0.05 using R and SAS 9.4. Results From 57 MRSA and 53 MSSA isolates, 320 peaks were identified. 31 significant peaks were identified, with 14 unique peaks for MRSA and 17 for MSSA. With S. aureus USA300, eight of the 31 peaks remained statistically significant. Conclusion MALDI-TOF MS can identify unique peak differences between MRSA and MSSA. This tool can be potentially used to distinguish S. aureus at the strain level in a clinical setting. MALDI-TOF MS can be an impactful and rapid diagnostic tool to detect antibiotic resistance in S. aureus in a clinical setting. Disclosures Lilly Immergluck, MD,MS, Melinta: Grant/Research Support|Melinta: Grant/Research Support

Objectives The aims of the study were to analyze the demographics, presentation, laboratory findings, and complications of pediatric Streptococcus pneumoniae meningitis since the introduction of the 13-valent pneumococcal conjugate vaccine, to improve recognition, and to minimize patient morbidity and mortality. Methods This study used a retrospective analysis of pediatric pneumococcal meningitis cases at 2 tertiary healthcare systems in the Southeastern United States from 2010 to 2018. Results We describe 21 cases of pneumococcal meningitis. All patients presented with fever, 95% had altered mental status by history or examination, and 48% had meningeal signs. Forty-three percent had seen another provider within 48 hours of admission. Forty-eight percent had delay in lumbar puncture (LP) of more than 6 hours after antibiotic administration, decreasing rates of positive cerebrospinal fluid cultures from 100% to 40% (P < 0.001). Decision to delay LP was due to either low suspicion for meningitis (n = 4) or clinical instability (n = 6) and was associated with lower rates of meningeal signs (P = 0.014) and higher rates of altered mental status on examination (P = 0.031). Fourteen patients (67%) were up-to-date on pneumococcal immunization. Serotypes were determined in 16 cases, with 2 patients (13%) immunized against the strain that infected them. Primary outcomes included seizures (48%), hearing loss (48%), cranial nerve palsy (33%), and death (5%). Delay in LP with low suspicion for meningitis was associated with longer hospital length of stay approaching statistical significance (P = 0.053). Conclusions Pneumococcal meningitis remains a relevant and potentially fatal disease despite widespread use of 13-valent pneumococcal conjugate vaccine. Its diagnosis is often delayed during interactions with physicians, which may put patients at increased risk for poor clinical outcomes.

Before the introduction of vaccines, group A rotaviruses (RVA) were the leading cause of acute gastroenteritis in children worldwide. The National Rotavirus Strain Surveillance System (NRSSS) was established in 1996 by the Centers for Disease Control and Prevention (CDC) to perform passive RVA surveillance in the USA. We report the distribution of RVA genotypes collected through NRSSS during the 2009–2016 RVA seasons and retrospectively examine the genotypes detected through the NRSSS since 1996. During the 2009–2016 RVA seasons, 2134 RVA-positive fecal specimens were sent to the CDC for analysis of the VP7 and VP4 genes by RT-PCR genotyping assays and sequencing. During 2009–2011, RVA genotype G3P[8] dominated, while G12P[8] was the dominant genotype during 2012–2016. Vaccine strains were detected in 1.7% of specimens and uncommon/unusual strains, including equine-like G3P[8] strains, were found in 1.9%. Phylogenetic analyses showed limited VP7 and VP4 sequence variation within the common genotypes with 1–3 alleles/lineages identified per genotype. A review of 20 years of NRSSS surveillance showed two changes in genotype dominance, from G1P[8] to G3P[8] and then G3P[8] to G12P[8]. A better understanding of the long-term effects of vaccine use on epidemiological and evolutionary dynamics of circulating RVA strains requires continued surveillance.

In this retrospective analysis, we describe weekly croup and corresponding viral prevalence patterns in a pediatric quaternary care system in metropolitan Atlanta. We characterize a series of 24 patients with croup associated with SARS-CoV-2 infection and show that this clinical presentation increased substantially in frequency during the period of high Omicron vs Delta transmission.

ANSWERS TO SELF-ASSESSMENT QUESTIONS 1. What is the term for the classification of myiasis whereby fly larvae require healthy, intact host tissue for development? a. Obligatory myiasis b. Facultative myiasis c. Accidental myiasis d. Pseudomyiasis Answer: a. Biologically, myiasis can be broadly classified into one of three groups: (i) obligatory myiasis, where the fly larvae require healthy host tissue as a nutritive source; (ii) facultative myiasis, where saprophagous larvae that normally colonize decaying organic substrates infest dead or dying tissue or preexisting wounds; and (iii) accidental or incidental myiasis, where the human body becomes colonized with free-living or facultative species that are not using host tissue as a nutritive source. Pseudomyiasis usually refers to contamination of a clinical specimen with a free-living species.

BACKGROUND Children with sickle cell disease (SCD) are at increased risk for bloodstream infections (BSIs), mainly because of functional asplenia. Immunizations and antibiotic prophylaxis have reduced the prevalence of invasive bacterial infections, but contemporary analysis of BSI in children with SCD is limited. METHODS We conducted a retrospective cohort study of children aged <18 years with SCD who had blood cultures collected at our institution from 2010 to 2019 to identify BSI. Probable contaminant organisms were identified and not included as BSI. We calculated the annual incidence of BSI at our institution with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS There were 2694 eligible patients with 19 902 blood cultures. Excluding repeated cultures and contaminant cultures, there were 156 BSI episodes in 144 patients. The median age at BSI was 7.5 years. The average incidence rate of BSI was 0.89 per 100 person-years (95% CI 0.45-1.32). The most common pathogens were Streptococcus pneumoniae (16.0%), Streptococcus viridans group (9.0%), Escherichia coli (9.0%), Staphylococcus aureus (7.7%), Bordetella holmesii (7.7%), Haemophilus influenzae (7.1%), and Salmonella species (6.4%). Odds of BSI were higher with sickle cell anemia genotypes (odds ratio [OR] 1.88; 95% CI 1.20-2.94) and chronic transfusions (OR 2.66; 95% CI 1.51-4.69) and lower with hydroxyurea (OR 0.57; 95% CI 0.39-0.84). CONCLUSIONS BSI remains a risk for children with SCD. Overall incidence, risk factors, and spectrum of pathogens are important considerations to guide prevention and empirical treatment of suspected infection in SCD.

ABSTRACT Background The goal of this study was to characterize the ability of school-aged children to self-collect adequate anterior nares (AN) swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Methods From July to August 2021, 287 children, age 4-14 years-old, were prospectively enrolled in the Atlanta area. Symptomatic (n=197) and asymptomatic (n=90) children watched a short instructional video before providing a self-collected AN specimen. Health care workers (HCWs) then collected a second specimen, and useability was assessed by the child and HCW. Swabs were tested side-by-side for SARS-CoV-2. RNase P RNA detection was investigated as a measure of specimen adequacy. Results Among symptomatic children, 87/196 (44.4%) tested positive for SARS-CoV-2 by both self- and HCW-swab. Two children each were positive by self- or HCW-swab; one child had an invalid HCW-swab. Compared to HCW-swabs, self-collected swabs had 97.8% and 98.1% positive and negative percent agreements, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups. Participants ≤8 years-old were less likely than those >8 to be rated as correctly completing self-collection, but SARS-CoV-2 detection did not differ. Based on RNase P RNA detection, 270/287 children (94.1%) provided adequate self-swabs versus 277/287 (96.5%) HCW-swabs (p=0.24) with no difference when stratified by age. Conclusions Children, aged 4-14 years-old, can provide adequate AN specimens for SARS-CoV-2 detection when presented with age-appropriate instructional material, consisting of a video and a handout, at a single timepoint. These data support the use of self-collected AN swabs among school-age children for SARS-CoV-2 testing.

Abstract Background Community-onset Staphylococcus aureus (CO-S. aureus) pediatric infections, methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) continue to contribute to the burden of infections seen in the ambulatory setting in the US. Individual risk factors have been identified, but place-based factors and specific geographic locality have not been well-studied. The purpose of this study is to predict place-based factors that contribute to the spread of CO-S. aureus in a major urban area using maximum entropy (MaxEnt), a machine learning technique. Methods Electronic medical records from two pediatric hospitals (2002 to 2016) were retrospectively reviewed. Inclusion criteria: a confirmed S. aureus infection within 48 hours of hospital admission (CO-S. aureus), < 19 years old, and a geo-referenced address within Atlanta’s metropolitan statistical area (MSA). Fourteen place-based factors, at the US Census block group level, were included in the MaxEnt models: < 18 years old, Caucasian, African American, ethnicity, poverty, education attainment, crowding, daycare, kindergarten enrollment, distance to K-12 school, distance to a children’s hospital, distance to a daycare center, and population density. A total of four models (CO-MRSA early, CO-MSSA early, CO-MRSA later, and CO-MSSA later) were run using the MaxEnt software. For each model, 75% and 25% of data was randomly assigned to training and testing groups, respectively. Models were assessed by jack-knife tests. Results 16,124 records met eligibility criteria for MaxEnt models. The training Area Under the Curve (AUC) ranged from 0.771 to 0.837 and the test AUC ranged from 0.769 to 0.804. Population density had the highest contribution in predicting CO-MRSA and CO-MSSA locations, which was confirmed by jack-knife tests. Conclusion By applying MaxEnt to pediatric CO-S. aureus infections in the Atlanta MSA, it was found that higher risks of CO-S. aureus infections may exist in more densely populated areas. MaxEnt can be utilized to identify potential future areas of CO-MRSA and CO-MSSA infections based on estimated or predicted changes to the place-based factors used to build these models. Disclosures Lilly Immergluck, MD, MS, GSK: Clinical Trial- PI|Merck: Vaccine Trial Site- serve as PI|Moderna: Board Member|Novavax: Part of CoVID-19 Phase 3 Trial through US Covid Prevention Network.

been sequenced; and far more samples have been sequenced than are represented in GISAID.In countries with a longer CST lag, the new variants may have enough time to establish themselves across a region 13 if quick tracking, tracing and actions to stop transmission are not undertaken.Therefore, this issue must receive urgent attention and bottlenecks that prevent a lower CST lag must be addressed.Overall, an effective genomic surveillance system requires not only sequencing a major fraction of SARS-CoV-2 strains from COVID-19 patients, but also rapid genome submission to open access platforms like GISAID.This will enable researchers across the globe to track the evolved variants and their mutations, epidemiology and biological consequences, which will provide crucial inputs for appropriate and effective public health policies

Although respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infections, the burden of RSV in children with sickle cell disease (SCD) is unknown.

While there has been significant progress in the development of rapid COVID-19 diagnostics, as the pandemic unfolds, new challenges have emerged, including whether these technologies can reliably detect the more infectious variants of concern and be viably deployed in non-clinical settings as “self-tests”. Multidisciplinary evaluation of the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW, a widely used rapid antigen test, included limit of detection, variant detection, test performance across different age-groups, and usability with self/caregiver-administration. While BinaxNOW detected the highly infectious variants, B.1.1.7 (Alpha) first identified in the UK, B.1.351 (Beta) first identified in South Africa, P.1 (Gamma) first identified in Brazil, B.1.617.2 (Delta) first identified in India and B.1.2, a non-VOC, test sensitivity decreased with decreasing viral loads. Moreover, BinaxNOW sensitivity trended lower when devices were performed by patients/caregivers themselves compared to trained clinical staff, despite universally high usability assessments following self/caregiver-administration among different age groups. Overall, these data indicate that while BinaxNOW accurately detects the new viral variants, as rapid COVID-19 tests enter the home, their already lower sensitivities compared to RT-PCR may decrease even more due to user error.

There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisystem inflammatory syndrome in children versus hospitalized control patients revealed differential cytokine responses, IgM/IgG/IgA epitope diversity, antibody binding and avidity. Apart from spike and nucleocapsid, IgG/IgA recognized epitopes in nonstructural protein (NSP) 2, NSP3, NSP12-NSP14 and open reading frame (ORF) 3a-ORF9. Peptides representing epitopes in NSP12, ORF3a and ORF8 demonstrated SARS-CoV-2 serodiagnosis. Antibody-binding kinetics with 24 SARS-CoV-2 proteins revealed antibody parameters that distinguish children with mild/moderate versus severe COVID-19 or multisystem inflammatory syndrome in children. Antibody avidity to prefusion spike correlated with decreased illness severity and served as a clinical disease indicator. The fusion peptide and heptad repeat 2 region induced SARS-CoV-2-neutralizing antibodies in rabbits. Thus, we identified SARS-CoV-2 antibody signatures in children associated with disease severity and delineate promising serodiagnostic and virus neutralization targets. These findings might guide the design of serodiagnostic assays, prognostic algorithms, therapeutics and vaccines in this important but understudied population.

BACKGROUND:Clinical laboratory testing has been an essential part of COVID-19 management. Serology can provide valuable information regarding a patient's exposure to virus, and may have a larger role to play as vaccines becomes available. Limited data is available on the serological response in pediatric patients. Here we investigate the use of one manufacturer's commercial assays for detecting IgM and IgG in an exclusively pediatric population.METHODS:Abbott SARS-CoV-2 IgM and IgG assays were performed on an Abbott ARCHITECT i1000. For specificity studies, we tested 78 patient specimens collected before the COVID-19 pandemic, and 66 specimens from patients who tested negative for SARS-CoV-2 nucleic acid amplification test (NAAT) during the COVID-19 pandemic. For sensitivity we tested 181 specimens from 41 patients with a positive NAAT result. Precision data was acquired for 20 days.RESULTS:For IgM, the highest qualitative positive agreement with molecular results was observed to be 15-30 days after a positive NAAT result or after symptom onset. For IgG, the highest positive agreement was 31-60 days after a positive NAAT result or 61-90 days after the start of symptoms. IgM started to decline 30 days after NAAT results and faded by 90 days. IgG started to decrease 60 days after a positive NAAT result.CONCLUSION:The Abbott IgM and IgG assays have negative agreements of 98.7-100% relative to NAAT results. The IgM and IgG levels assayed by these methods start to decline months after positive molecular results and onset of symptoms in a pediatric population.

Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the "RADxSM Tech Test Verification Core" and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school. Focal points included: laboratory and clinical device evaluation of the limit of viral detection, sensitivity, and specificity of devices in controlled and community settings; regulatory expertise to provide focused attention to barriers to device approval and distribution; usability testing from the perspective of patients and those using the tests to identify and overcome device limitations, and engineering assessment to evaluate robustness of design including human factors, manufacturability, and scalability.