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Purpose Chronic granulomatous disease (CGD) is an uncommon, inborn error of immunity. We updated our large, single-center US experience with CGD and describe some newly recognized features. Methods We retrospectively reviewed 26 patients seen from November 2013 to December 2019. Serious infections required intravenous antibiotics or hospitalization. Results There were 21 males and 5 females. The most frequent infectious agents at presentation were aspergillus (4), serratia (4), burkholderia (2), Staphylococcus aureus (2), and klebsiella (2). The most common serious infections at presentation were pneumonia (6), lymphadenitis (6), and skin abscess (3). Our serious infection rate was 0.2 per patient-year from December 2013 through November 2019, down from 0.62 per patient-year from the previous study period (March 1985–November 2013). In the last 6 years, four patients were evaluated for human stem cell transplantation, two were successfully transplanted, and we had no deaths. Several patients had unusual infections or autoimmune manifestations of disease, such as pneumocystis pneumonia, basidiomycete/phellinus fungal pneumonia, and retinitis pigmentosa. We included one carrier female with unfavorable Lyonization in our cohort. Conclusion We update of a large US single-center experience with CGD and describe some recently identified features of the illness.

Background Streptococcus pyogenes (GAS) is the major cause of bacterial pharyngitis in children. GAS can cause conditions ranging from asymptomatic pharyngeal carriage to invasive infection. We compared the genomic characteristics of GAS pharyngeal and invasive isolates from U.S. children. Methods We cultured GAS from throat swabs collected from children aged 3–18 years with acute GAS pharyngitis, diagnosed by rapid antigen or molecular test, and from a convenience sample of asymptomatic children during 1/2020 to 3/2022 in Chicago, IL; Atlanta, GA; Portland, OR; Phoenix, AZ. We collected invasive isolates in Chicago. Whole-genome sequencing (WGS) was performed on the Illumina MiSeq for species confirmation, isolate typing, and virulence and antimicrobial gene identification. Reference-based read alignment was used for whole genome phylogenetic analysis. Results Of 1144 collected throat swabs, 684 were from children with pharyngitis and 460 from asymptomatic children. 13 invasive GAS isolates were collected. GAS were cultured from 359 pharyngitis and 20 asymptomatic swabs. Of these, 371 GAS isolates could be recovered and underwent WGS. Thirty isolates (8%) were either low-quality sequences and/or identified as species other than S. pyogenes and were excluded. Whole-genome phylogenetic analysis of 341 GAS (215 pharyngitis, 13 asymptomatic, 13 invasive) identified 25 related clusters and 8 singletons (Figure 1). Virulence gene complements within given emm types were generally concordant with recently published CDC strain data. The most frequently identified resistance genes were tetM and ermB. 281 isolates (82%) carried no antibiotic resistance genes. Some clusters were significantly more represented at certain sites within apparent geographically defined clusters of nearly indistinguishable isolates (Figure 1): cluster 1 in Chicago, emm type 3; cluster 14 in Phoenix and Portland, emm 28, 12; and cluster 15 in Atlanta, emm 89. No major genomic factors were significantly associated with asymptomatic vs pharyngitis vs invasive presentation. Figure 1:Whole genome phylogenetic tree of pediatric GAS isolates Maximum likelihood phylogenetic analysis based on whole-genome alignment of 371 Group A Streptococcus isolates. Tip colors represent cluster assignments based on genetic similarity. Inner ring represents geographic location of GAS isolation. Outer ring represents patient presentation: asymptomatic colonization, symptomatic pharyngitis, or invasive infection. Conclusion Pharyngeal and invasive GAS in children within individual clonal complexes are co-included in closely related clusters, with evidence of close transmission within individual sites Disclosures All Authors: No reported disclosures.

Background COVID-19 affected the epidemiology of many respiratory pathogens including GAS. Assessing genetic heterogeneity (emm type, antimicrobial resistance, virulence factors) can inform treatment recommendations and targets for potential GAS vaccines. We assessed GAS clinical antibiotic susceptibility and performed whole genome sequencing (WGS) among pediatric pharyngeal isolates from 2020–2022. Methods From 1/2020–3/2022 we collected throat swabs in pediatric clinics and EDs from children aged 3-18 years in Chicago, IL; Atlanta, GA; Portland, OR; and Phoenix, AZ: 1) with acute GAS pharyngitis and 2) among a convenience sample of asymptomatic children to assess for GAS colonization. Swabs were plated on blood agar. E-tests were used to assess clinical susceptibility to erythromycin (ERY) and ciprofloxacin (CIP). emm type and antimicrobial resistance genes (ERY, Clindamycin (CLI), and fluoroquinolones) were assessed by WGS. Results 1144 pharyngeal swabs were collected: 359/684 (52%) from children with GAS pharyngitis by rapid test and 20/460 (4.3%) from asymptomatic children yielded GAS on culture. Phenotypic resistance: 55/364 (15%) tested isolates were ERY resistant and 5/364 (1.4%) CIP resistant. The proportion of isolates with ERY resistance increased significantly from 2020 (6%) to 2021–2022 (25%) (χ2 = 23.70, p< .00001) (Figure 1). MICs were high among ERY resistant GAS (Table 1). Genotypic resistance: Of 304 sequenced GAS isolates 40/304 (13%) were ERY resistant, 35/304 (11.5%) were both ERY resistant and CLI (inducible or constitutive) resistant, and 4/304 (1.3%) fluoroquinolone resistant. ermB (62%) was the most common gene for ERY resistance and constitutive CLI resistance, followed by ermTR (23%) and ermT (11%) both conferring inducible CLI resistance. Among the 20 isolates from asymptomatic children no ERY, CLI, or CIP resistance occurred, and no resistance genes were identified. emm types 11, 9, 77, 58 and 94 were associated with ERY and CLI resistance. Conclusion ERY resistance increased from 2020–2022. The high rate of CLI resistance among ERY resistant GAS was associated with erm genes. These results are important to inform treatment recommendations for GAS pharyngitis and targets for vaccine development that can reduce antimicrobial-resistant GAS disease. Disclosures All Authors: No reported disclosures.

Background The COVID-19 pandemic has affected respiratory disease epidemiology. Measures to reduce transmission of SARS-CoV-2 (e.g., masking, social distancing, school closures) have reduced the incidence of common infectious diseases. At least one early report described changes in rates of pediatric GAS pharyngitis. We sought to determine the difference in GAS pharyngitis rates before and after the onset of the pandemic at our children’s hospital. Methods Clinical pharyngeal specimens tested for GAS by rapid antigen tests (RADTs) or LAMP methodology (loop-mediated isothermal amplification of GAS DNA) from January 2019 to March 2022 at our children’s hospital were analyzed. Clinician’s evaluating patients for GAS pharyngitis perform a RADT, when positive the patient is treated for GAS pharyngitis. When the RADT is negative, a LAMP test is performed. Patients were considered test-positive if either test was positive regardless of clinical symptoms. Annual positivity rates were compared using statistical process control (SPC) charts with both 2019 and 2020 as baseline years (i.e., 2019 vs 2020-3/2022; 2020 vs 2021-3/2022). The change in GAS incidence rate (positive patients/1000 tested) between years was assessed by chi-square tests. Results 9,896 patients had throat swabs tested for GAS from January 2019 through March 2022. Using SPC with 2019 as a baseline, there was a 15.1% decrease in mean GAS positivity through 3/2022. With 2020 as baseline, there was a 13.0% decrease in mean GAS positivity through 3/2022. The incidence of positive GAS tests decreased significantly: 2019 vs. 2020-3/2022 (x2 = 84.97, p ≤0.00001) and 2020 vs. 2021-3/2022 (x2 = 154.01, p ≤0.00001). Figure 1. Conclusion Using throat swab results, the incidence of pediatric GAS pharyngitis at our hospital has decreased significantly during the COVID-19 pandemic. Implications: Pandemic-related risk mitigation measures, such as masking, social distancing, and school closures, were associated with significantly decreased incidence of GAS pharyngitis. It is likely that GAS colonization and invasive infections were also affected. Disclosures All Authors: No reported disclosures.

Introduction: We recently reported that luminal myofibroblastic proliferation (LMP) is an active process of smooth muscle-cell derived myofibroblasts and their matrix products that can cause progressive coronary artery (CA) stenoses in KD patients. Serial echocardiography to assess for high risk CA changes, with periodic cardiac functional assessments in selected patients, is the current standard of care for monitoring patients with CA abnormalities. Monitoring for LMP/chronic thromboses is not routinely performed. Hypothesis: We hypothesized that echocardiographic images from KD children with severe CA abnormalities could suggest the presence of LMP and/or chronic thromboses, indicating the potential for progression to CA stenoses. Methods: We reviewed echocardiographic studies from a convenience sample of 28 KD patients with multiple aneurysms/giant aneurysms, to determine whether LMP and/or thrombosis could be identified on serial imaging. Results: In 12 of the 28 patients, images were highly suggestive of LMP and/or thromboses. This could only be assessed in the proximal segments of the left main, circumflex, left anterior descending and right CAs. Detection was enhanced by optimizing the depth and sector width for the coronary artery segment of interest and use of magnification on the review station. Variations in echocardiographic techniques such as low frequency probes, harmonics, persistence, excessive compress or low gain settings made the assessment difficult. 4 patients in this cohort required CA bypass and 1 died from myocardial infarction due to progressive LMP. Distal vessel occlusion could not be visualized by echocardiography. Conclusions: Images highly suggestive of LMP/chronic thromboses were evident in at least a third of patients with severe CA disease, including one patient who died of progressive LMP stenosis documented at autopsy. Echocardiography could not distinguish between LMP and chronic thrombosis as the cause of CA stenoses. Our study highlights the need for improved serial imaging for ongoing LMP/thromboses in AHA risk group IV. Patients with these complications may require more frequent cardiac functional assessments than are routinely recommended, to avoid adverse outcomes.