bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &gt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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