bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1944. The Natural History of SARS-CoV-2 Infection in Infants and the Role of Subsequent Infections on Protection: A Prospective Cohort in Mexico City
Authors: Molina-Sanchez Alejandra , Rodriguez-Dorantes Laura Angelica , Rajme-López Sandra , Ramos-Cervantes Pilar , Cline Allison R , Staat Mary A , Ruiz-Palacios Guillermo Miguel
Published: January 2025

Background

Limited information exists regarding the natural history of SARS-CoV-2 infection in infants, including the proportion of asymptomatic disease. Moreover, the impact of repeated infections on immunity and clinical presentation is unknown. The possibility of non-severe symptoms related to viral variants has not been explored.

Incidence rate of SARS-CoV-2 first and subsequent infections.

Methods

This meticulous prospective cohort study, conducted from January 1st 2022 to March 30th 2024, followed healthy newborns with weekly rtPCR. Upon respiratory symptoms or a positive rtPCR, subjects were evaluated and a daily symptomatic record was kept for 14 days. Positive samples were sequenced. Incidence rates were calculated for infection and reinfection. Symptoms were grouped according to organ and system involvement. Descriptive and logistic regression analyses were performed in R 4.3.3.

Results

Of 1181 eligible newborns, 796 were included and followed for 10,774 child-months. Nasal swab yield was 76%. Fifty two percent were male, 67% were exclusively breastfed, and none were vaccinated against SARS-CoV-2. A total of 559 SARS-CoV-2 infections were detected (423 first, 109 second, 23 third, and 4 fourth infections). The incidence rate was 5.1 cases per 100 child-months (Figure 1). One subject had severe COVID-19.

The most common symptoms for first infection were rhinorrhea (51%), cough (49%), irritability (39%), and fever (36%). Asymptomatic infection was more common in reinfections than first infections (44 vs 25%, p=0.001) (Table 1). The frequency of asymptomatic infection progressively increased from 25% to 35% and 78% for the first, second, and third infections (p 0.02; X2 for trend).

Subjects with throat, eyes, and skin symptoms were more likely to be infected with the BA.1/BA.2 variants. Those with systemic disease were more likely to be infected by the BA.4/BA.5. Asymptomatic infection tended to be more common in infections by the XBB/EG variants (Table 2). The odds of having an asymptomatic infection increased in subjects with ≥ 2 infections. (Table 3).

Conclusion

SARS-CoV-2 infection is common in infants, though predominantly non-severe. Asymptomatic infections are frequent. Subsequent infections conferred protection against symptomatic infection. The clinical characteristics of COVID-19 differ according to the viral variant.

Disclosures

Mary A. Staat, MD, MPH, Cepheid: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria
P-1947. Risk of Severe COVID-19 Reinfection among Persons Hospitalized with a Primary COVID-19 Infection, Minneapolis-St. Paul, Minnesota
Authors: Wienkes Haley , D’Heilly Paige , Bye Erica , Meyer Stephanie , Como-Sabetti Kathryn , Lynfield Ruth
Published: January 2025

Background

SARS CoV-2 continues to circulate broadly making it important to understand risk factors for severe illness when reinfection occurs. We used CDC COVID-19 Hospitalization Surveillance Network (COVID-NET) data to assess reinfection, hospitalization at reinfection (hospitalized reinfection) and ICU admission at reinfection (ICU reinfection) by underlying medical conditions and ICU admission at primary infection.

Methods

Nonpregnant adults hospitalized 3/9/2020 - 9/30/2021 were identified through COVID-NET, surveillance that includes Minneapolis-St. Paul metropolitan area residents with a positive SARS-CoV-2 result during or ≤ 14 days before admission. Cases were matched to all reports of persons positive for SARS-CoV-2 to identify reinfections, defined as a positive SARS-CoV-2 test > 90 days after the initial positive result through 4/17/2024. Logistic regression was used to assess reinfection and severity of reinfection adjusted for age, sex, race/ethnicity, and vaccination status (aOR).

Results

6,434 hospitalized persons met the COVID-NET case definition for their primary infection; 1,189 (18%) had a reinfection. 356 (30%) of the reinfection cases were hospitalized and 51 (14%) of those hospitalized had ICU admission. Having any underlying condition was associated with reinfection (aOR 1.62, 95% CI 1.18, 2.23) and hospitalized reinfection (aOR 2.16, 95% CI 1.27, 3.69). Cardiovascular disease was associated with reinfection (aOR 1.72, 95% CI 1.28, 2.31). Cardiovascular disease (aOR 3.03, 95% CI 1.87, 4.90), blood disorders (aOR 2.42, 95% CI 1.03, 5.37), and renal disease (aOR 1.85, 95% CI 1.12, 3.06) were associated with hospitalized reinfection. All 51 ICU reinfections and 14 reinfection deaths had an underlying condition. Primary ICU admission was not associated with reinfection or hospitalized reinfection but was associated with ICU reinfection (aOR 5.26, 95% CI 1.65, 16.73).

Conclusion

Among patients hospitalized with COVID-19, underlying conditions and primary ICU admission were associated with severe outcomes during reinfection. These results highlight the continued importance of prevention strategies like vaccination and treatment to mitigate severe illness among patients at highest risk.

Disclosures

All Authors: No reported disclosures
P-1953. Youden’s Index Ensures the Accuracy of Wastewater-based Surveillance of SARS-CoV-2 Variants by Allele-Specific RT-qPCR or Genomic Sequencing
Authors: Kabir Md Pervez , Mercier Elisabeth , Hegazy Nada , Nguyen Tram B , Wong Chandler H , Pisharody Lakshmi , Shen Wan , D’Aoust Patrick M , Tyson Graber , Delatolla Robert
Published: January 2025

Background

Clinical genomic surveillance is the gold standard for monitoring SARS-CoV-2 variants globally, but as the pandemic wanes, reduced testing increases the risk of missing the emergence of variants of concern or failing to accurately follow their trajectory in populations. Wastewater-based genomic surveillance (WWS) that estimates variant frequency based on its defining set of alleles derived from clinical genomic surveillance has been successfully implemented. However, this method has its challenges, and allele-specific (AS) RT-qPCR that monitors a single, variant-defining, allele is used as a complementary method for estimating variant prevalence. Demonstrating equivalent performance of the methods is a prerequisite for their continued application of WWS in current and future pandemics.Figure 1:Comparison of AS-RT-qPCR and amplicon-based sequencing methods for estimating SARS-CoV-2 variants frequency in wastewaters; A) N: D63G and B.1.617.2 haplotype, B) N: P13L and B.1.1.529 haplotype, C) S: H69+/V70+ and BA.1 haplotype, and D) S: H69-/V70- and BA.2 haplotype.

Methods

We compared single-allele frequency estimation using AS-RT-qPCR, to single-allele or haplotype frequency estimations derived from amplicon-based sequencing to estimate variant prevalence in municipal wastewater collected during emergent and prevalent periods of Delta, Omicron, and two of its sub-lineages in Ottawa, Canada.Table 1:Youden index of targeted alleles (N: D63G, N: P13L, S: H69+/V70+ and S: H69-/V70-) in wastewaters using AS-RT-qPCR and sequencing as well as haplotype of each variant.

Results

We found that all three methods of frequency estimation were concordant and contained sufficient information to describe the trajectory of variant prevalence in wastewater across time (Figure 1). We further evaluated the accuracy of these methods by quantifying the diagnostic performance (i.e., method accuracy expressed as Youden’s index), based on available clinical genomic prevalence data. Youden’s index confirms the accuracy of methods employed for variant frequency estimation in wastewater (Table 1), but accuracy of each method can be influenced by different factors.

Conclusion

WWS emerges as a crucial epidemiological tool for monitoring infectious disease in the population during the COVID-19 pandemic. This study validates the accuracy of WWS in SARS-CoV-2 variants monitoring using AS-RT-qPCR or sequencing methods and provides comprehensive perspective for implementing public health interventions against infectious diseases.

Disclosures

All Authors: No reported disclosures
P-1971. Patterns of T cell receptor usage reveal associations with COVID-19 severity
Authors: Lu Zhongyan , Parsons Emily , Richard Stephanie A , Alba Camille , Sukumar Gauthaman , Rosenberger John , Zhang Xijun , Burgess Timothy , Agan Brian , Dalgard Clifton , Pollett Simon , Malloy Allison M
Published: January 2025

Background

T cells are associated with viral clearance and improved outcomes in COVID-19, but also with immunopathology. Defining T cell diversity in response to SARS-CoV-2 infection enables implementation of T cells in prevention and treatment strategies. T cells recognize peptide sequences from pathogens upon presentation in major histocompatibility complexes (MHC). Human MHC molecule diversity results in a wide array of peptide recognition by T cells making viral escape difficult, but also challenging to measure.

Methods

Using the ImmunoSEQ Assay to sequence complementarity-determining regions in the β chains (CDR3β) of the T cell receptor (TCR) from peripheral blood collected from participants in the EPICC COVID-19 cohort study, we quantified and characterized patterns of TCR usage. Multiple bioinformatic pipelines were compared for analysis.

Results

Our study evaluated TCR repertoires from 39 participants who had mild (20 outpatient) versus severe (19 hospitalized) acute COVID-19, and either experienced unvaccinated primary infection (n = 15) or vaccine breakthrough infection (n = 24) (Table 1). From these four clinical groups, we used the ImmuneCODE database, VDJdatabase and healthy controls to identify CD8 TCR sequences and amino acid motifs in the CDR3β region specific for the SARS-CoV-2 proteome. We were surprised to find that vaccine breakthrough and primary infection participants exhibited similar frequencies of SARS-CoV-2-specific TCR sequences over 14-21 days post-symptom onset. Increased use of common TCR clones occurred in participants with older age and comorbidities, which correlated with more severe disease (Figure 1). Strikingly, an increased frequency of non-SARS-CoV-2 TCRs was significantly associated with severe disease in unvaccinated (p = 0.006) and vaccinated participants (p = 0.045).

Conclusion

In conclusion, our study highlights the opportunities and challenges of studying the complexity of T cell diversity and the utility of combining databases and bioinformatics for identification of patterns of TCR recognition. Interestingly, participants who were hospitalized were more likely to have circulating T cells non-specific for SARS-CoV-2 suggesting that vaccines that increase T cell specificity may reduce disease severity.

Disclosures

Simon Pollett, MBBS, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response
P-1976. Incidence and Outcomes of Community-Onset Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections in the Pre- and Post-COVID-19 Pandemic
Authors: Chung Jessica , Hmu Tun May Thet , Htet Soe Khin Htet , Mee Aung Tin Mee , Zin May Thu , Liu Franklin , Ghitan Monica , Chapnick Edward , Lin Yu Shia
Published: January 2025

Background

Methicillin-susceptible Staphylococcus aureus (MSSA) is a pathogen linked to significant morbidity and mortality. CDC reported that the incidence of MSSA bloodstream infections (MSSA-BSI) significantly increased from 2012 to 2017, though mortality rates were unchanged. The COVID-19 pandemic may affect the incidence and mortality of MSSA-BSI due to the use of dexamethasone, delay in diagnosis due to quarantine, or the misdiagnosis of BSI as COVID-19. Our objective was to compare the incidence and outcomes of community-onset MSSA-BSI pre- and post-pandemic.

Methods

This retrospective cohort study evaluated community-onset MSSA-BSI, defined as a positive blood culture within 72 hours of admission in hospitalized adults. The study population was divided into the pre-COVID group (June 1, 2018 to December 31, 2019) and the post-COVID group (January 1, 2022 to June 30, 2023). Patients with BSI other than MSSA, hospitalized within 30 days, transferred from another facility, and immunosuppressed were excluded. The Whitney Mann U test and chi-square test were used for the analysis.

Results

The study included 101 patients with MSSA-BSI: 48 in the pre-group, and 53 in the post-group. More than half of the patients were Caucasian males with a median age of 70 and 67 years in the pre- and post-group, respectively. The primary source of MSSA-BSI was skin and soft tissue, followed by respiratory, osteoarticular, and intravascular line-related infections.

The post-group had more cases who delayed seeking medical care and higher scores on the Charlson Comorbidity Index and Pitt bacteremia score. The post-group had a longer median length of stay (LOS) compared to the pre-group (15 vs. 10 days), p=0.022. The ICU admission rate and in-hospital mortality rate of pre- and post-group were 12.5% vs. 28% and 14.5% vs. 22.6%. However, neither of these measures were statistically different, p=0.051 and p=0.301 respectively.

Conclusion

While the number of community-onset MSSA-BSI cases was similar, the post-group was more likely to delay seeking medical care and have longer LOS. The COVID-19 pandemic has impacted clinical care, leading to delayed medical attention, increasing disease severity. Our study highlights the importance of clinician awareness and patient education on early recognition of MSSA-BSI.

Disclosures

All Authors: No reported disclosures
P-1995. A Nationwide Cohort Study of Delta and Omicron SARS-CoV-2 Outcomes and Vaccine Effectiveness amongst Individuals with Chronic Heart Failure or Ischemic Heart Disease
Authors: Wee Liang En , Loy Enoch Xueheng , Lim Jue Tao , Tan Sharon , Lye David , Tan Kelvin Bryan
Published: January 2025

Background

Individuals with heart failure (HF) / ischemic heart disease (IHD) have poorer outcomes following respiratory viral infections; however, data is lacking on outcomes and Vaccine Effectiveness (VEs) following SARS-CoV-2 infection with newer COVID variants.

Methods

Outcomes of Delta/Omicron SARS-CoV-2 infection in a highly vaccinated/boosted cohort of adult Singaporeans with HF/IHD were contrasted against matched population controls. Matching was conducted based on age, sex, ethnicity, socioeconomic status, and comorbidities. Cox regressions were used to compare risk of infection, COVID-19-related hospitalisations and severe COVID-19 disease and estimate VEs.

Results

15,426 HF patients and 110,442 IHD patients were matched to 41,221 and 223,843 population controls, respectively. Compared with controls, higher risk of COVID-19 hospitalisation and severe disease was observed amongst HF cases during Delta (hospitalisation: adjusted-hazards-ratio, aHR=1.40[1.20-1.62]; severe-COVID-19: aHR=1.66[1.28-2.14]) and Omicron (hospitalisation: aHR=1.77[1.65-1.90]; severe-COVID-19: aHR=2.40[2.10-2.75]). Higher risks were also observed for infected IHD patients, albeit to a smaller extent (Omicron, hospitalization: aHR=1.21[1.17-1.26]; severe-COVID-19: aHR=1.12[1.03-1.21]). During both Delta and Omicron waves, the risk of COVID-19-related infection, hospitalisation and severe disease was significantly lower in boosted groups compared against those who had only received 2 doses. VEs were comparable with controls for IHD, with lower effectiveness observed against hospitalisation amongst HF patients (3 doses aHR=0.42[0.37-0.48]; 4 doses aHR=0.28[0.23-0.34]) compared to controls (3 doses: aHR=0.28[0.23-0.34]; 4 doses: aHR=0.18[0.16-0.22]).

Conclusion

Higher risks of severe COVID and comparable VEs suggest that it is more cost effective to boost IHD/HF patients. Lower VEs amongst HF patients point to the need for more boosters to achieve similar rates of protection.

Disclosures

All Authors: No reported disclosures
P-2008. Chronic Conditions as Risk Factors for COVID-19–Associated Hospitalization Among Adults, 2022-2023
Authors: Hamid Sarah , Derado Gordana , Pham Huong , Woodruff Rebecca C , Sachdev Darpun , Kawasaki Breanna , Meek James , Witt Lucy S , Ryan Patricia A , Kim Sue , Bye Erica , Akpo Jennifer , Rowlands Jemma , Licherdell Erin , Shiltz Eli , Sutton Melissa , Talbot Keipp , Price Andrea , Havers Fiona P , Taylor Christopher
Published: January 2025

Background

Risk factors for COVID-19-associated hospitalizations were identified early in the pandemic. Since then, population immunity to SARS-CoV-2 has increased substantially and hospitalizations for COVID-19 have decreased. Identifying populations at greatest risk of COVID-19–associated hospitalization can help guide prevention and treatment efforts. We aimed to update information on chronic conditions as risk factors for COVID-19-associated hospitalization.Figure.Flow diagram of participant selection into analytic population, Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), 2 October 2022–30 September 2023.

Methods

We compared hospitalization rates in adults aged ≥ 18 years with vs without 9 chronic conditions during 2 October 2022–30 September 2023. Rate numerators were COVID-19–associated hospitalization counts from the COVID-19–Associated Hospitalization Surveillance Network, a population-based active surveillance system with a 98-county catchment area in 13 states. Rate denominators were counts of adults with and without chronic conditions in the catchment area, estimated with US census county-level population data and state-level estimates of the adult population with and without select chronic conditions from the 2022 Behavioral Risk Factor Surveillance System. Rate ratios and 95% confidence intervals were estimated using Poisson regression with Monte Carlo simulation, adjusting for age group, sex, and race/ethnicity.

Results

Among 3,500 hospitalized adults, 74% had ≥ 1 chronic condition (Figure, Table 1). Hospitalization rates were higher among those with ≥ 1 chronic condition (vs none); adjusted rate ratios (aRR) ranged from 2.2 in adults aged ≥ 75 years to 4.6 in adults aged 18-49 years (Table 2). Among adults overall, chronic kidney disease was associated with the greatest risk of COVID-19–associated hospitalization (aRR: 4.5), followed by diabetes (2.2), history of stroke (2.0), severe obesity (2.0), coronary artery disease (1.9), COPD (1.9), smoking (1.6), and asthma (1.5); results varied by age and generally attenuated with older age (Table 2). Adjusting for number of chronic conditions, hospitalization rates were higher for adults aged ≥ 75 years relative to 18–49 years (18.5) (Table 3).

Conclusion

Of 9 chronic conditions, 8 were associated with increased risk of COVID-19–associated hospitalization with risk varying by condition and age group. Older age remains the strongest risk factor.

Disclosures

Sue Kim, MPH, Council of State and Territorial Epidemiologists: Grant/Research Support
P-2014. Online Clinician Education Curriculum Results in Performance Changes in Clinical Practice Related to Incorporating COVID-19 Antiviral Therapies for Non-Hospitalized Patients
Authors: Nair Arun S , Uravich Maria B , Capparelli Catherine
Published: January 2025

Background

This study examined whether online continuing medical education (CME/CE) focused on evidence-based best practices for incorporating COVID-19 antiviral therapies in non-hospitalized patients would result in improved identification of high-risk patient groups and the adoption of new clinical practices.

Methods

Clinicians who participated across a curriculum of 3, live and online, 30-minute CME/CE video discussions between experts. Performance was assessed by inviting learners to complete a survey 30-60 days post-education, identifying practice changes and the degree to which clinicians experience barriers to those changes. The data was collected from 11/29/2022 to 06/21/2023.

Results

There were 232 learners consisting of PCPs, Emergency Medicine Physicians, ID Specialists who completed the survey. The analyses from the 3 programs showed that approximately 98% of learners made a practice change or had practices reinforced due to education. Five key practice changes that were modified/implemented as a result of the education included:Identifying patients at higher risk for developing severe COVID-19-related complications (69%)Incorporating new information about treatment options for non-hospitalized patients with COVID-19 (67%)Ensure patients receive treatment within the appropriate therapeutic window (60%)Educating patients on COVID-19 and available antiviral treatments (58%)Screening patients for potential DDIs prior to COVID-19 antiviral initiation (55%)Some of the barriers to implementing these practice changes include:Patients present outside the recommended treatment windowUnfamiliar with potential drug-drug interactions for COVID-19 antiviralsPatient concerns or questions regarding available antiviralsUnfamiliar with guideline recommendations for available antiviralsLack of time during office visits to educate patients on the importance of timely testing and treatment

Conclusion

The practice changes identified in this assessment provide compelling evidence that participation in online CME/CE prompts adoption of changes in practice related to COVID-19 antiviral therapies in non-hospitalized patients.

Acknowledgement: This education was supported by an independent educational grant from Pfizer Inc. and Merck & Co, Inc.

Disclosures

All Authors: No reported disclosures
P-2024. Multiple Cases of the Delta Substrain AY.29 with Casirivimab/Imdevimab Escape Mutation Identified in a Nosocomial COVID-19 Outbreak in a Hematology Ward
Authors: Hamada Yuka , Kawamura Hideki , Shinkawa Naomi , Kuroda Makoto , Kamiya Hajime
Published: January 2025

Background

Underlying immunodeficiencies are a concern due to the risk of persistent infections of SARS-CoV-2. The Delta Substrain AY.29 with casirivimab/imdevimab escape mutations was detected from patients who was diagnosed as a COVID-19 while hospitalized in a hematology ward. This study aims to investigate the factors leading to casirivimab/imdevimab escape mutations and to propose measures to strengthen the control of nosocomial COVID-19 infections.Figure 1.Epidemic curve based on the day of positive SARS-CoV-2 PCR test (A) and on the symptom onset day (B) of COVID-19 outbreak.Epidemic curves based on onset symptom date (B) exclude 21 cases with asymptomatic or unknown onset date. Cases 1-3 and medical staff are COVID-19 infected patients with casilivimab/imdevimab escape mutation strains detected

Methods

We conducted an active epidemiological investigation to the COVID-19 outbreak occurred at the hematology ward in one regional hospital in Southern part of Japan. In addition to collecting demographic information on patients, we created a network diagram that integrates the results of genomic analyses to evaluate the factors associated with casirivimab/imdevimab escape mutation.Figure 2.Results of genome analysis of virus isolated from cases in this COVID-19 outbreak (n=30)★; strains with casilivimab escape mutation⋆; strains with imdevimab escape mutation

Results

In this outbreak, a total of 44 COVID-19 patients were identified (Figure 1), including 30 inpatients and 14 medical staff or family members. Initially, the strains detected from the cases were identical gene sequences of the Delta strain, and 24 cases were treated with casirivimab/imdevimab. However, three patients with lymphatic hematologic diseases 26-32 days after initial diagnosis tested positive for SARS-CoV-2 infection. The samples detected from these patients had G446V mutation, indicative of imdevimab escape mutant, with mutations indicative of casirivimab escape, such as K417T (1 strain), L455F (1 strains, G476D (2 strains), and G476S (1 strain) (Figure 2). The medical staff, who had been working in the dialysis unit prior to the outbreak, first became symptomatic two months after the outbreak and was diagnosed with COVID-19 by PCR. His samples revealed a mutant strain detected in three patients.

Conclusion

The results suggest that patients with immunocompromised, especially lymphatic diseases, who being treated with casirivimab/imdevimab may not be sufficiently eradicated the virus from the body even if their symptoms improve. This may have caused the virus acquire mutations. When casirivimab/imdevimab are administered to immunocompromised patients, it is important that periodic viral testing should be performed. Accurate infection control measures must be implemented to prevent the spread of the mutant strain unnoticed.

Disclosures

All Authors: No reported disclosures
P-2039. Prognostic factors of disease progression in patients with mild-to-moderate COVID-19 on early remdesivir treatment in Taiwan
Authors: Ho Yu-Chien , Chang Min-Chi , Lin Wen-Ying , Wu Chia-Ying , Liu Szu-Yu , Chuang Chien , Juan Chih-Han , Liu Chia-Jen , Lin Yi-Tsung
Published: January 2025

Background

An early 3-day course of remdesivir treatment was recommended for high risk patients with mild-to-moderate COVID-19. We investigated the prognostic factors of disease progression and mortality in patients with mild-to-moderate COVID-19 who were treated with a 3-day course of remdesivir in Taiwan.

Methods

Adult patients with mild-to-moderate COVID-19 treated with a 3-day course of remdesivir at Taipei Veterans General Hospital from April–July 2022 were identified. The main outcomes were 14-day disease progression (defined as increased oxygen requirement compared with the baseline condition or mortality) and 28-day mortality. Logistic regression was used to identify independent variables associated with poor outcomes.

Results

Among the 345 patients on early remdesivir treatment with a 3-day course, 62 patients (18%) had 14-day disease progression, and 5 patients (1.4%) died within 28 days. Eighty patients (23.2%) did not receive COVID-19 vaccine before the diagnosis of COVID-19. Body mass index, cardiovascular disease, Charlson Comorbidity Index, and secondary bacterial infection were independent factors associated with 14-day disease progression, and nosocomial COVID-19 was the only independent factor associated with 28-day mortality. In 233 patients (67.5%) administered at least two doses of COVID-19 vaccine, 38 patients (16.3%) had 14-day disease progression, and 4 patients (1.7%) died within 28 days. Female sex, cardiovascular disease, and secondary bacterial infection were independent factors for 14-day disease progression. Nosocomial COVID-19 and C-reactive protein levels >10 mg/dL were independent factors associated with 28-day mortality.

Conclusion

Nosocomial COVID-19 and secondary bacterial infections predisposed these patients to poor outcomes, regardless of vaccination. Therefore, infection control measures are important in the fight against COVID-19.

Disclosures

All Authors: No reported disclosures
P-2087. Clinical Application of Broad-Range PCR in Pediatric Patients
Authors: Gagliardo Christina , Halabi Katia Camille , Singer David , Qurbanali Sarah , Davydova Maria , Katragkou Aspasia
Published: January 2025

Background

Broad-range PCR (BRPCR) and next-generation sequencing (NGS) have the potential to be useful adjunctive tools in diagnosing the infectious etiology of a wide range of pediatric infections. We aimed to assess the clinical utility and application of BRPCR and NGS in children with suspected infections.

Methods

A retrospective chart review was performed on pediatric patients with clinical samples sent for BRPCR (University of Washington Molecular Microbiology Laboratory, Seattle, WA, USA) between January 2023 and December 2023. Data was extracted from the electronic medical record, and descriptive statistics were performed.

Results

51 patients had 55 samples sent for BRPCR. The demographics and sample information are listed in Table 1. A total of 18 (35.3%) patients had an organism identified on culture or BRPCR that was contributory to the clinical picture. Of those, 4 (7.3%) were identified on culture but not on BRPCR, and 6 (11%) were identified on BRPCR but not on culture. 4 (7.3%) cases identified the same organism on culture and BRPCR, while 4 (7.3%) cases identified different organisms on culture and concomitant BRPCR. In 6 (11.8%) cases, antibiotics were de-escalated, and in 7 (13.7%) cases, antibiotics were discontinued.

Conclusion

BRPCR can be a valuable adjunct to identifying causative organisms in children with suspected infections and can help tailor antibiotic management. Our results highlight the potential impact of BRPCR results to reduce broad-spectrum antibiotic use. Further studies are needed to guide the optimal use of BRPCR and determine its clinical impact on management of pediatric infections.

Disclosures

All Authors: No reported disclosures
P-2092. Evaluation of Daptomycin for MicroScan Dried Gram Positive MIC Panels from a Multicenter Assessment of Select Gram Positive Species
Authors: Dawa Kristianne , Brookman Regina , Diaz Jose , Hastey Christine
Published: January 2025

Background

Given the need for accurate antimicrobial susceptibility testing results to support patient care decisions, data were evaluated from clinical isolates of Staphylococcus aureus and Enterococcus faecalis on an investigational MicroScan Dried Gram Positive MIC (MSDGP) panel with daptomycin.*

Methods

Data from a previous multicenter study conducted at four sites were analyzed by comparing MIC values obtained using the MSDGP panels to MICs from a CLSI broth microdilution reference panel. A total of 444 Staphylococcus aureus and 114 Enterococcus faecalis clinical isolates were analyzed. These isolates were tested using the turbidity and Prompt methods of inoculation on MSDGP panels. The panels were incubated at 35 ± 1°C and read on the WalkAway System, the autoSCAN-4 instrument, and visually. Read times for the MSDGP panels were at 16-20 hours. Frozen reference panels were prepared and read according to CLSI methodology.

Results

Essential agreements were calculated comparing MIC results from the MSDGP panels with MIC results from frozen panels for all isolates tested in efficacy and challenge phases and are found in the following table.

Conclusion

Daptomycin MIC results for Staphylococcus aureus and Enterococcus faecalis obtained with the MSDGP panel correlate well with MICs obtained using frozen reference panels in this multicenter study.

*Pending submission and clearance by the United States Food and Drug Administration; not yet available for in vitro diagnostic use in the US.

For Investigational Use Only. The performance characteristics of this product have not been established.

©2024 Beckman Coulter. All rights reserved. All other trademarks are the property of their respective owners.

Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries.

May be covered by one or more patent. See www.beckmancoulter.com/patents.

2024-12909

Disclosures

Kristianne Dawa, n/a, Beckman Coulter: employee Regina Brookman, BS, Beckman Coulter: employee Jose Diaz, BS, Beckman Coulter: employee Christine Hastey, PhD, Beckman Coulter: employee
P-2093. A 30-year Descriptive Analysis of Mycobacterium szulgai Infections
Authors: Vega Pool Tobar , Vikram Holenarasipur R , McGary Alyssa
Published: January 2025

Background

Mycobacteirum Szulgai is a non-tuberculous mycobacterium known to cause human disease. Descriptions in the literature are limited to case reports and a larger case series from the Netherlands. Guidelines from the American Thoracic Society recommend that M. szulgai should always be considered pathogenic and that treatment should be based on in-vitro susceptibilities.

Demographics and patient characteristics

Methods

We embarked on a retrospective study of adults ( >18 years) with M. szulgai infection at the Mayo Clinic sites in Arizona, Minnesota, and Florida. We queried the Mayo Clinic Database using two different search methods, (Advanced Text Explorer and the Mayo Data Explorer) using the terms ‘Mycobacterium Szulgai,’ ‘Mycobacteria Szulgai’,’ M. Szulgai’ and ‘Szulgai.’ Medical records from 1994 to 2023 were reviewed.

Diagnostic studies

Results

Initial search yielded 43 patients. Twenty-seven patients were excluded (incomplete records or prior history of infection treated elsewhere). For our cohort of 16 patients, the mean age was 65 years [IRQ 57-74 years], 13 of those were caucasian. Five patients [31%] were immunosuppressed. Thirteen patients [81%] developed pulmonary infection, 5[31%] had extra pulmonary infection (2[12%] with disseminated disease and 3[19%] with extra-pulmonary disease without primary pulmonary infection). Only 8 [50%] patients received specific therapy. All treated patients met ATS criteria for NTM infections, while 3 [19%] untreated patient met criteria. Only 4 [25%] patient received therapy based on susceptibilities. The most common regimen was a combination of rifampin, ethambutol and macrolide in 5[31%] of the patients. Seven patients [47%] were cured, 4[27%] had ongoing symptoms, 1[7%] had relapse and 1 [7%] is currently receiving therapy. There were 2[ 13%] deaths in the untreated group and none from the treated group. One patient was lost to follow up.

Treatment and outcomes

Conclusion

Our findings echo published literature and ATS recommendations that M. szulgai should be regarded as a true pathogen that necessitates targeted therapy.

Disclosures

All Authors: No reported disclosures
P-2095. Ultrasensitive Clostridioides difficile Toxin A/B Assay (in Development) for Higher Diagnostic Accuracy
Authors: Dave Gipshu , Truong Tiffany , Soban Mariya , Nguyen Justin , Zaugg Frank , Brachet Valerie , Wagner Peter , Sandlund Johanna
Published: January 2025

Background

Diagnostic tests for Clostridioides difficile infection (CDI) have either poor sensitivity or specificity, which has led to guideline recommendations for complex multistep testing algorithms. Ultrasensitive C. difficile toxin A/B measurements correlate with disease and may offer a standalone solution for CDI diagnosis. Fluxus develops ultrasensitive, target-agnostic, and low-complexity single-molecule diagnostic instruments based on optofluidic technology that combines integrated optics and microfluidics on a single chip-based system. Here, we report on the preliminary analytical performance of C. difficile toxin A and B assays (in development) powered by the Fluxus technology.

Methods

C. difficile toxin A (TcdA) and B (TcdB) were spiked into buffer and stool (pooled) and tested across a wide range of TcdA/TcdB concentrations to give dose-response curves and estimate limits of detection (LoD; assay background +2.5 STD of background) and quantification (LoQ; assay background +10 STD of background). TcdA and TcdB concentrations were calculated from a four-parameter logistic nonlinear regression-based calibration curve. Crossreactivity between the toxins was assessed. Further evaluation of expanded analytical and clinical performance is ongoing.

Results

LoDs in buffer for the prototype TcdA and TcdB assays were 0.47 and 0.98 pg/mL, respectively, and LoQs were 0.91 and 3.34 pg/mL, respectively, with a high dynamic range. LoDs in spiked stool for the TcdA and TcdB assays were 2.02 and 1.15 pg/mL, respectively, and LoQs were 4.25 and 4.35 pg/mL, respectively. There was no crossreactivity between the assay targets across a 4-log dynamic range.

Conclusion

Fluxus’ ultrasensitive C. difficile toxin A/B assays in development can detect TcdA and TcdB at pg/mL concentrations. Preliminary evaluation of spiked stool samples indicates a comparable dilution linearity to calibrator dose response in buffer. An ultrasensitive C. difficile toxin A/B assay has the potential to provide both high clinical sensitivity and specificity and may replace current testing methods.

Disclosures

Gipshu Dave, MS, Fluxus, Inc.: Stocks/Bonds (Public Company) Tiffany Truong, MS, Fluxus, Inc.: Stocks/Bonds (Public Company) Mariya Soban, MS, Fluxus, Inc.: Stocks/Bonds (Public Company) Justin Nguyen, BS, Fluxus, Inc.: Stocks/Bonds (Public Company) Frank Zaugg, PhD, Fluxus, Inc.: Stocks/Bonds (Public Company) Valerie Brachet, PhD, Fluxus, Inc.: Stocks/Bonds (Public Company) Peter Wagner, PhD, Fluxus, Inc.: Stocks/Bonds (Public Company) Johanna Sandlund, MD, PhD, Fluxus, Inc.: Stocks/Bonds (Public Company)
P-2101. Coverage Of The Molecular Diagnostic Technology For Pulmonary Tuberculosis In Bangladesh: Diagnostic Milestone For Control Of Tuberculosis
Authors: Khan Ahmadul Hasan , Yeasmin Shakila , Anjum Sanjida , Monirul Haque F M
Published: January 2025

Background

Provision of early and accurate Tuberculosis (TB) diagnosis is crucial to end TB specially in a densely populated like Bangladesh. Molecular WHO-approved rapid diagnostic tests for TB (mWRDs) can significantly improve identification of undiagnosed TB cases. This study estimates the coverage of mWRDs among the total detected Pulmonary TB (PTB).

Methods

Monthly programmatic data on nationwide TB diagnosis in Bangladesh using mWRDs were pulled and compiled. Routine programmatic data for TB detection using mWRDs were segregated and compared quarterly for the first three quarter of 2023 to know the percentage of molecular testing coverage among presumptive TB tested and percentage of pulmonary TB notified diagnosed through molecular testing during that time.

Results

A total of 5,53,172 presumptive cases undergone mWRDs to detect the Mycobacterium Tuberculosis (MTB) and Rifampicin Resistant (RR) cases. Among them, 80,414 (14.54%) cases were detected as MTB including RR. During the 1st, 2nd, and 3rd quarters of 2023, the total number of presumptive tests conducted were 133,845, 175,038, and 244,289, respectively. Among them, the detected TB cases according to each quarter were 15,418 (11.52%), 24,397 (13.94%), and 40,599 (16.62%), respectively (Figure 1). With this data it was obvious that in the 3rd quarter of 2023 the percentage of case detection by mWRDs increased compared to the consecutive previous two quarters. It revealed that, percentage of case detection by mWRDs gradually increased over the time during 1st to 3rd quarter 2023. To assess the coverage of mWRDs, quarterly data was analyzed and compared. It was determined how many TB cases were confirmed using molecular technology (GeneXpert and TrueNat) out of the total number of pulmonary cases over time. The analysis revealed that the quarterly percentage coverage of mWRDs was 26.85%, 42.68%, and 68.89% during the 1st, 2nd, and 3rd quarters, respectively, indicating an increasing trend over time (Figure 2).

Conclusion

Scaling up the mWRDs as a point of care diagnostic test for presumptive TB cases in resource limited settings would have a significant impact to meet the SDG and End TB strategy for TB detection. Increasing coverage of molecular testing for more PTB case detection is inevitable considering the context of Bangladesh.

Disclosures

All Authors: No reported disclosures
P-2104. A Quality Improvement Project that Implements Multi-disciplinary Residency Training on Point-of-Care (POCUS) Assistance for Lumbar Punctures (LP) in Infants < 6 Months
Authors: Locke Nathaniel , Glenn Daniel , Kelly Connor , Hull Aicha , Sainato Rebecca
Published: January 2025

Background

LPs are critical in the work-up febrile infants to evaluate for meningitis. National data suggests many clinicians struggle to perform this procedure successfully which leads to additional procedures, delayed treatment, and unnecessary hospitalization/antimicrobials. There is evidence that suggests POCUS assistance leads to greater LP success as it is uniquely suited to visualize the infant spine in great detail, which can provide critical information (Figure 1). By increasing POCUS application and awareness, we hope to obtain cerebral spinal fluid (CSF) from > 90% of infants < 6 months within 3 attempts, and before antibiotics in > 75% of cases.

Methods

Utilizing our institution’s electronic medical record (EMR), we reviewed all infants < 6 months admitted to the pediatric ward who had an LP from January 2021 to June 2023 to establish our baseline. Hands-on and didactic training on POCUS-assistance for LP in neonates were provided to multiple residency faculty, and training was integrated within each programs’ curriculum. We created a post-procedural survey and perform quarterly EMR reviews of our progress.

Results

Baseline: CSF was obtained in 33/35 infants (94%). The average number of attempts was 3, interquartile range (IQR) 1-3, and max 10. 14/35 infants (40%) received antibiotics before a sample was obtained. The average time from antibiotics to obtaining an LP was 8.8 hours, IQR 1.4-6.2 hours. 16 infants (46%) had either a traumatic LP or no CSF obtained, including 7 (20%) where LP occurred following antibiotics.

Post-implementation: All interns in family practice, pediatrics, and emergency medicine now receive training on POCUS-assistance for obtaining LPs in infants (Table 1). 7 surveys have been completed and 3 infants were admitted to our ward with concern for meningitis. CSF was obtained in all 3 prior to antibiotics and within 3 attempts (Table 2).

Conclusion

Our EMR review is congruent with national data, suggesting a high rate of LP failure in infants. A new multi-disciplinary curriculum has been established at our hospital and POCUS assistance is now routinely being used for obtaining LPs in those < 6 months. While we have limited post-implementation data, our results show promise towards increasing success, reducing attempts, and decreasing time to antibiotics.

Disclosures

All Authors: No reported disclosures
P-2105. Concordance of Multiplexed Molecular Lower Respiratory Panel with Standard Culture Method and Potential Clinical Impact on Antimicrobial Therapy
Authors: Patel Nisha M , Gitman Melissa R
Published: January 2025

Background

Pneumonia is the most common cause of health-care associated infections. The mainstay of diagnosis is respiratory culture, which is limited by up to 72-hour turnaround time and variable sensitivity. An added challenge is the emergence of antimicrobial resistance, which may confound the choice for empirical therapy. Rapid diagnostic tests have been developed to mitigate the challenges of diagnosis and treatment, but the clinical impact is not known. The Unyvero Lower Respiratory Tract Panel (LRT) is a qualitative multiplex nucleic acid test that can detect DNA of 20 microorganisms and 10 resistance genes in respiratory samples, with a 5-hour turnaround time. We hypothesized that use of the LRT on respiratory samples may have an impact on antimicrobial therapy and, consequently, antimicrobial stewardship.

Methods

The LRT was performed on a random sample of 48 respiratory tract specimens that were obtained inpatient. We assessed concordance of LRT with standard-of-care (SoC) testing. We performed a retrospective chart review for the clinical context in which specimens were obtained (infection suspected versus not) and to determine whether use of LRT would have had an impact on antimicrobial therapy at the time of care.

Results

Of 48 specimens, 25 (52%) had concordance between LRT and SoC testing and the remaining 23 specimens (48%) had discordance between LRT and SoC testing. Notably, 8 (17%) “discordant” specimens had organisms grow on culture that have no targets on the LRT (Candida species, Klebsiella aerogenes, Burkholderia cepacia complex, Streptococcus anginosus). In 3 cases where a resistance gene (CTX-M, mecA) was identified by LRT, antimicrobial susceptibility testing was compatible. In 7 cases, antibiotic therapy may have been impacted by use of LRT; in 5 cases therapy may have been initiated unnecessarily, and in 2 cases additional therapy may have been warranted. There were no cases where de-escalation of antibiotics would have been warranted.

Conclusion

The Unyvero LRT panel is an appealing diagnostic tool due to fast turnaround time, but a significant clinical impact due to its use has not yet been demonstrated. Though our study was limited by sample size, we found that LRT may have increased inappropriate use of antibiotics, rather than promoting stewardship.

Disclosures

Melissa R. Gitman, MD, Biomerieux, Inc: Grant/Research Support
P-2106. Streamlining Care Delivery in the Pediatric Emergency Department Using Rapid Point-Of-Care Molecular Diagnostics For Group A Streptococcus: A Randomized Controlled Trial
Authors: Pernica Jeffrey , Kam April J , Smaill Fiona , Ewusie Joycelyne , Khan Sarah , Elliott Shakeap , Sung Melani , Doan Quynh , Smieja Marek , Thabane Lehana , Goldfarb David
Published: January 2025

Background

As per IDSA guidelines, throat swab testing for group A Streptococcus is important to ensure appropriate antimicrobial use for children with pharyngitis that is not obviously viral. Bacterial culture is the diagnostic reference standard but takes days to result. With culture, physicians often initially provide a prescription that is only to be filled later on if GAS testing is positive. Unfortunately, this strategy can result in inappropriate treatment if parents of children with negative tests fill the script anyway, or if parents of children with positive tests cannot be contacted later. Point-of-care (POC) antigen testing in children is specific but not sensitive, so a negative test still requires culture verification, which limits its overall usefulness. POC molecular GAS testing is as sensitive as culture, and provides a result in minutes, which simplifies prescribing.

ED physician satisfaction at enrolment

Satisfaction was captured using a 5-point Likert scale on the day of enrolment.

Methods

A randomized controlled trial was done in a Canadian children’s emergency department (ED). Children aged >3 y with throat swabs ordered to diagnose GAS pharyngitis were eligible. Participants were randomized 1:1 to either the IDNOW Strep A2 (intervention) or bacterial culture (control). The primary outcome was appropriate treatment, ie taking antibiotics if GAS-positive or not taking antibiotics if GAS-negative. Secondary outcomes included physician and parent satisfaction and time to symptom resolution.

Caregiver satisfaction at enrolment

Satisfaction was captured using a 5-point Likert scale on the day of enrolment.

Results

392 participants were recruited from Jan 2021 – Mar 2024. Intervention and control groups were similar in terms of mean age (8.2 vs 8.3 y) and mean MacIsaac score (both 3.3); 29% of the intervention group and 41% of the control group were GAS-positive. Participants in the intervention group were significantly more likely to receive appropriate antibiotics (90.8% vs 76.3%, OR 3.1 [95%CI 1.7-5.7], p< 0.001). ED physicians (pOR 147, p< 0.001) and parents (pOR 2.4, p< 0.001) were also much more likely to be satisfied with POC molecular testing. There were no statistically significant differences in time to resolution of symptoms, though comparisons favoured the intervention.

Conclusion

In the largest RCT of molecular GAS testing yet done, the intervention was associated with substantial improvements in appropriate antibiotic prescribing and was clearly preferred by both ED physicians and parents.

Disclosures

Jeffrey Pernica, MD, MSc, FRCPC, DTMH, MedImmune: Grant/Research Support|Merck: Grant/Research Support