bluuebunny/crossref_metadata_2025_split huggingface dataset:
288. Prognostic Factors for In-hospital Mortality of Patients with Severe COVID-19 Hospitalized in the University Medical Center, Lithuania
Authors: Kubiliute Ieva , Urboniene Jurgita , Rudenaite Akvile , Zablockiene Birute , Gefenaite Giedre , Jancoriene Ligita 
Published: December 2022

Abstract

Background
Till May 2022 there were 1.06 million of COVID-19 cases and 9108 deaths caused by COVID-19 disease registered in Lithuania. The objective of the study was to evaluate prognostic factors for in-hospital mortality of patients with severe COVID-19 disease.

Methods
COVID-19 positive adult patients hospitalized in Vilnius University Hospital Santaros Klinikos, Lithuania, were included in the cohort study between March 2020 and December 2021. Medical history, vital signs were collected, laboratory tests, chest X-ray were performed. Severe COVID-19 disease was defined as pneumonia with objective respiratory failure symptoms. ROC curve was used to evaluate prognostic value of a laboratory test, multivariable logistic regression was used to determine the prognostic factors for in-hospital lethal outcome. p-value &lt; 0.05 was considered significant.

Results
Severe COVID-19 disease was diagnosed for 291 participants, 21 (7.2%) of them died. Hematological, lung diseases and cancer were more common among patients who died compared to those who recovered (Table 1). Patients who died were older, more frequently had confusion (25.0% vs 5.2%, p=0.001), tachypnea (57.1% vs 26.7%, p=0.003), and dyspnea (81.0% vs 54.1%, p=0.017), their time median from symptoms onset to admission was shorter (2.5 (IQR 0-7) vs 7 (IQR 4-9) days, p&lt; 0.001) compared those who recovered. On admission, patients who died had lower lymphocytes count, higher neutrophiles count and higher concentration of aspartate aminotransferase (AST), lactate, creatinine and urea compared to those who recovered. The best prognostic features for lethal outcome possessed neutrophiles count, AST, lactate, creatinine and urea (Figure 1). Optimal cut-off values were calculated and included into multivariable regression model. Multivariable regression revealed that hematological diseases (OR 8.68; 95% CI 1.46-51.40, p=0.017), initial AST &gt; 32.9 U/l (OR 13.57; 95% CI 1.46-125.94, p=0.022), lactate &gt; 1.46 mmol/l (OR 4.87; 95% CI 1.03-22.86, p=0.045) were associated with in-hospital mortality of patients with severe COVID-19 adjusted for age.

Conclusion
Hematological diseases, elevated AST and lactate are significant prognostic factors for in-hospital mortality of patients with severe COVID-19 disease at earlier stages of disease.

Disclosures
All Authors: No reported disclosures.
290. Quantitative Antibody Levels Against SARS-CoV-2 Spike Protein in Children with COVID-19 and MIS-C
Authors: Avcu Gulhadiye , Arslan Sema Yıldırım , Soylu Mehmet , Bilen Melis , Çiçek Candan , Bal Zümrüt Şahbudak , Kurugöl Nuri Zafer , Ozkinay Ferda 
Published: December 2022

Abstract

Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has different clinical courses in children and adults. The majority of coronavirus diseases 2019 (COVID-19) caused by SARS-CoV-2 are either mild or asymptomatic in children.
This report aimed to determine quantitative antibody levels against SARS-CoV-2 spike protein in children with COVID-19 and MIS-C.

Methods
A single-center retrospective study was conducted at a tertiary-level university hospital. Seventy-five pediatric patients diagnosed with COVID-19 and MIS-C were included between September 2021 and February 2022.
The demographic, clinical and laboratory data of cases were extracted from medical records. The duration of hospitalization, management, and outcomes was reported.
Quantitative antibody levels against SARS-CoV-2 spike protein in the third month after the initial diagnosis was measured, and patients were also evaluated for post-COVID-19 syndrome symptoms .

Results
The patients were categorized into three disease phenotypes; there were 36 (48%) patients with mild/asymptomatic (group1)( M/F 20/16, mean age, 11.4 years) 22 (29.3%) patients with moderate to severe SARS-CoV-2 infection (group 2)(M/F 13/9, mean age, 13 years) and 17 (22.6%) patients with MIS-C (group 3)( M/F 9/8, mean age, 10.1 years).
The majority of the children in group 1 (80.6%), in group 2(90.9%), and in group 3(82.4%) had a detectable IgG antibodies to SARS-CoV-2 spike protein(p=0.567). The mean antibody values against SARS-CoV-2 spike protein was 321.9±411.6 in group 1, 274±261 in group 2, and 220±299 in group 3 (p &gt;0.05).
The antibody positivity rate was similar in patients with COVID-19(85.5%) and MIS-C (82.4%) (p=0.833). The mean antibody value against SARS-CoV-2 spike protein was 303.9±360.3 in the COVID-19 group and 220 ±299 in the MIS-C group(p &gt;0.05).

Conclusion
The majority of the children had a detectable IgG antibody level to SARS-CoV-2 spike protein. There was no difference between asymptomatic/mild disease, moderate/severe disease, and MIS-C groups in mean antibody levels. Long-term studies are needed to examine antibody responses over time in children with COVID-19 and MIS-C for different vaccination schedules.

Disclosures
All Authors: No reported disclosures.
309. Genetic Diversity and Conservation of Envelope Gene of SARS-CoV-2 and its Variants B.1.1.7, B.1.351, P.1, B.1.617.2 and B.1.1.529 with comparison with other human coronaviruses
Authors: Liu Benjamin 
Published: December 2022

Abstract

Background
SARS-CoV-2 E gene PCRs have been widely used as the first-line assay with a higher sensitivity than those targeting N or RdRp gene. Given the currently available primers and probes were designed at the onset of the pandemic, it is unknown whether the SARS-CoV-2 VOCs have accumulated significant mutations that may affect E gene PCRs. In this study we aim to perform a comprehensive genetic analysis of SARS-CoV-2 E gene sequences to evaluate the impact of the emerging VOCs on E gene PCR performance.

Methods
600 whole-genome sequences of 7 species of human coronaviruses (HCoVs) were retrieved from GenBank and GISAID, including Sarbecoviruses (SARS-CoV-2 variants B1.1.7, B1.351, P.1, B.1.617.2 and B.1.1.529, and SARS-CoV), Embecovirus (OC43, HKU1), Merbecovirus (MERS) and Alphacoronaviruses (229E, NL63). The E gene sequences were retrieved from full-length genomes of corresponding viruses and aligned by ClustalW multiple alignment. Phylogenetic, conservation and mutation analyses analysis of the enrolled sequences was performed.

Results
E gene-based phylogenetic analysis yielded HCoVs typing results consistent with whole genome typing, suggesting E gene is a reliable locus for phylogenetic analysis and typing of HCoVs. Four pan-Sarbecovirus conserved E gene regions were identified with 100% conserved nucleotide similarity among SARS-CoV-2 and its VOCs, as well as SARS-CoV. These regions have appropriate G/C content which may be suitable for primer/probe design for E gene-based pan-Sarbecovirus screening assay. No significant E mutations were found in 137 retrieved SARS-CoV-2 and its VOCs. Interestingly, two novel variations, C26299U and T26354A, were identified in two of our SARS-CoV-2 strains. The latter variation occurred at the 3’ end of the target region of the widely used Charité/Berlin (WHO) probe. This variant may lead to a potential failure of the first-line E gene PCR.

Conclusion
Our data shed light on the genetic diversity and conservation of E gene of SARS-CoV-2 and may be beneficial for future primer/probe design for novel first-line assay or SARS-CoV-2-specific E gene PCR. SARS-CoV-2 VOCs have not accumulated significant mutations in E gene so far. The impact of novel E gene variations C26299U and T26354A on molecular diagnostic testing warrants further investigation.

Disclosures
All Authors: No reported disclosures.
310. Longitudinal Assessment of Point-of-Care LumiraDx Antigen and Antibody Test Performance During Acute SARS-CoV-2 Infection and Recovery
Authors: Dalmat Ronit , Prabhu Roshni , Bauer Marie , Ikuma Matthew H , Hamilton Daphne , Rechkina Elena A , Cantera Jason L , Grant Benjamin D , Drain Paul K 
Published: December 2022

Abstract

Background
Rapid COVID-19 tests can offer significant advantages and reduce health disparities. The LumiraDx SARS-CoV-2 platform can perform microfluidic fluorescence assays for the rapid detection of SARS-CoV-2 antigen (Ag) and antibodies (Ab). We evaluated both tests in a longitudinal cohort to evaluate performance during acute SARS-CoV-2 infection and recovery.

Methods
We collected nasal samples from 71 unique participants at four clinic visits spanning 0-21 days since symptom onset (DSSO); blood samples were collected from the same participants over six visits spanning 0-87 DSSO. For Ag testing, 232 anterior nasal swabs were assayed by: 1) the LumiraDx Ag test, 2) a laboratory-based electrochemiluminescence immunoassay for N Ag, 3) RT-PCR (Hologic Panther Fusion), and 4) culture (growth in VeroE6AT cells). For Ab testing, 308 serum samples were assayed by: 1) the LumiraDx Ab test and 2) Roche Elecsys Anti-S SARS-CoV-2 total Ab test. Measures of concordance [positive predictive agreement (PPA), negative predictive agreement (NPA), and Cohen’s Kappa (Κ)] were estimated for qualitative results of the LumiraDx tests versus corresponding lab reference tests. Confidence intervals were estimated via bootstrapping.

Results
LumiraDx Ag results had strong agreement with lab N-Ag results (Κ &gt; 0.80) across all samples. Between 0-5 days, agreement was perfect, except for one sample resulting positive by LumiraDx Ag and negative by lab Ag. Agreement with PCR results was moderate overall (Κ=0.60), though substantial (Κ &gt; 0.6) for both 0-5 DSSO (PPA=0.96/NPA=0.80) and 6-10 DSSO (PPA=0.96/NPA=0.59). Agreement with culture results was moderate overall (Κ=0.46): substantial (Κ=0.6) between 0-5 DSSO (PPA=0.96/NPA=0.60) and fair (Κ=0.29) between 6-10 DSSO (PPA=1.0/NPA=0.32).
LumiraDx Ab results showed almost perfect agreement with lab Ab results across all samples (Κ=0.88), with substantial agreement (Κ &gt; 0.7) for samples collected 0-10 DSSO (PPA=0.93/NPA=0.89) and 11-28 DSSO (PPA=0.99/NPA=0.69).
Longitudinal agreement of LumiraDx antigen test result and culture positivity, by PCR Ct value.
Nasal samples grouped by participant (lines) and agreement of results between LumiraDx antigen test result and culture positivity (proxy for infectiousness).

Conclusion
LumiraDx rapid tests perform well compared to more costly and time-consuming lab methods of Ag and Ab detection. The rapid Ag test may be helpful in identifying patients infectious between 0-5 DSSO, given the substantial concordance of the rapid Ag test and culture positivity.

Disclosures
Daphne Hamilton, BA, Roche (spouse is employed by Roche): Employee.
315. Standardized Measurement of SARS-CoV-2 Viral Load Over Time in Respiratory Compartments and in Response to Remdesivir Treatment
Authors: Beckwith Curt , Sam Soya , Novitsky Vladimir , Shin Jimin , Lethbridge Kevin , Steingrimsson Jon , Sahu Sujata , Rapoza Kim , Chandran Karen , Mariano Vincent J , Bazerman Lauri , Hipolito Evelyn R , Diaz Isabella , Carnevale Daniella M , Gillani Fizza S , Caliendo Angela , Kantor Rami 
Published: December 2022

Abstract

Background
Two years into the pandemic, clinicians do not have access to a standardized measurement of SARS-CoV-2 viral load (VL) that allows for VL comparison across clinical specimens and different assays. Reliable VL measurement in diverse respiratory specimens, over time, and in response to treatments such as remdesivir (RDV), could better inform treatment and prevention.

Methods
To investigate the use of a standardized VL assay in respiratory specimens, we enrolled patients hospitalized with COVID-19 in Providence, RI, with/without RDV exposure; collected serial samples from 4 compartments (nasopharyngeal-NP, nasal-NA, oropharyngeal-OP, saliva-SA) in 3 visits during the 1st week of hospitalization; and characterized SARS-CoV-2 VL using a ChromaCode HDPCR™ quantitative research use only assay, calibrated to the first World Health Organization (WHO) International Standard (IS). Linear mixed effects models and associated regression coefficients were used to analyze inter-compartmental VL differences at enrollment, over time, and with/without RDV.

Results
Of 35 participants (60% male; 70% White, 14% Hispanic/Latino, 49% RDV exposure), all had visit 1 samples (median hospital day 1, IQR 0-2; pre-RDV for those exposed); 80% visit 2 samples (median hospital day 2, IQR 1-8); and 37% visit 3 samples (median hospital day 4, IQR 3-7). Overall, 38 NP, 67 NA, 57 OP, and 67 SA samples were collected. Mean log VLs (Log10IU/mL) differed by compartment at visit 1 (NP 6.3, NA 4.9, OP 4.1, SA 5.6, p=0.0001) and significantly decreased over time in all compartments (p&lt; 0.04 for all comparisons). Log VL change over time was not significantly different between compartments or between people treated/not treated with RDV.

Conclusion
We successfully measured respiratory intercompartmental SARS-CoV-2 VL differences among hospitalized patients using a standardized assay calibrated to the WHO IS. Dissemination of standardized VL measurement methods will allow accurate VL comparisons across assay types quantified in IU/mL and improve assessment of the impact of COVID-19 treatments. Inter-compartmental VL differences at baseline may indicate sampling variability or different viral burden. RDV did not appear to accelerate viral decay.

Disclosures
Curt Beckwith, MD, Gilead Sciences, Inc: Grant/Research Support Jon Steingrimsson, PhD, Gilead: Grant/Research Support Angela Caliendo, MD, PhD, ChromaCode: Advisor/Consultant|Danaher/Cepheid: Advisor/Consultant|First Light: Advisor/Consultant|Hologic: Grant/Research Support|ID Connect: Advisor/Consultant|Quidel: Advisor/Consultant|Visby: Advisor/Consultant Rami Kantor, MD, Gilead Sciences: Grant/Research Support.
320. Clinical Impact of Metagenomic Next Generation Sequencing in a Large Pediatric and Adult Cohort
Authors: Lehman Alice , Goren Lea , Toles Olivia , Andrews Shannon L , Thielen Beth K , Drozdov Daniel , Rubin Nathan 
Published: December 2022

Abstract

Background
Plasma metagenomic next-generation sequencing (mNGS) is an emerging diagnostic tool. As the clinical use of mNGS increases, efforts to better understand the role of mNGS in diagnosis and management of infectious diseases are essential. Current literature is limited to small retrospective reviewers and a prospective study therefore subject to institutional variability. Here, we aim to describe the use, sensitivity, time to diagnosis, clinical impact, and cost effectiveness of mNGS in the largest patient cohort to date.

Methods
We included pediatric and adult patients who had plasma mNGS testing as part of care from December 2017 through December 2021 at University of Minnesota (UMN). Patients were identified using the Karius database. Electronic medical records were reviewed for every mNGS test, recording patient demographics, underlying conditions, indications, and results within 30 days of mNGS. All cases were assessed by 2 reviewers including one board-certified infectious diseases doctor. Sensitivity of mNGS was determined relative to conventional tests. The primary end point was change in clinical management. Secondary end points included accuracy, time to diagnosis, and infectious disease consultation. UMN IRB approved this study as non human subjects research.

Results
584 mNGS tests were ordered in the study period, with 203 reviews completed to date. Solid organ transplantation (SOT) (32%) was the most common underlying condition, followed by hemopoietic stem cell transplantation (HSCT) (28%). Fever (45.8%), then pulmonary findings (26%) were the most common indications for ordering mNGS. Conventional and mNGS tests identified an infectious cause of the clinical syndrome in 49% of cases, while a contaminant was found in 52% of cases. The sensitivity of mNGS in identification of infectious cause was 47%, approximately 7% more sensitive than conventional testing. Despite this increased sensitivity, mNGS changed clinical management in 20% of cases.

Conclusion
mNGS demonstrated superiority in accurate detection of infectious causes of clinical syndromes, however, changed clinical management in a minority of cases, suggesting timing of the mNGS test is critical. This study identified SOT and HSCT as high yield patient groups for implementation of a prospective study.

Disclosures
Beth K. Thielen, MD, PhD, Horizon: Advisor/Consultant|Horizon: Honoraria|Merck: Grant/Research Support.
334. Clinical Outcomes with Implementation of Accelerate Pheno Blood Culture Detection System for Gram Negative Bacteremia
Authors: Lee Shu Xian , Wu Benita Y , Suter Kurt , Lokant Matthew S , Ward Andrew , Spigelmyer Amy E , Freeman Lauren K , Thompson Jesse M , Demkowicz Ryan , Howard Catessa A , LaSala Rocco , Reece Rebecca 
Published: December 2022

Abstract

Background
Bacteremia is a life-threatening illness. Delayed treatment increases patient morbidity and healthcare costs. Accelerate Pheno™ Blood Culture Detection System (AXDX) is a novel diagnostic technology for rapid detection of gram-negative bacteremia. Studies have shown accurate and faster time to speciation and sensitivity (TTSS) by AXDX compared to conventional modality. Our unique study examined the direct impact of AXDX on clinical outcomes and cost.

Methods
This retrospective study consisted of 213 patients aged 18 years and older admitted to our academic institution with gram-negative bacteremia. The pre-AXDX group had 109 patients admitted in 2019 and the post-AXDX group had 104 patients admitted in 2021. Demographics, microbes, TTSS, time to de-escalation of therapy (TTDeT), length of stay (LOS), readmissions, mortality rates, and Clostridioides difficile infection (CDI) rates were recorded.

Results
The pre-AXDX group had 51.4% females, mean age of 60.3 years, mean Charlson Comorbidity Index (CCMI) of 2.2, mean LOS of 21.2 days, and mean Pitt Bacteremia Score (PBS) of 2.4. The post-AXDX group had 52.0% females, mean age of 63.7 years, mean CCMI of 3.0, mean LOS of 15.0 days, and mean PBS of 2.7. Both groups’ top 2 sources of bacteremia were urinary and gastrointestinal and top 2 microbes were Escherichia coli and Klebsiella pneumoniae. Pre-AXDX's mean TTSS was 71.9 hours and 23.6 hours for post-AXDX. Pre-AXDX's mean TTDeT was 74.0 hours and 43.9 hours for post-AXDX. The pre-AXDX cohort had 7.4% more related readmissions, 5.5% more CDI, and 0.3% more inpatient mortality than post-AXDX group.

Conclusion
In addition to faster TTSS with AXDX as seen with previous studies, our study shows clinical advantages with AXDX use. Both groups were comparable in bacteremia sources and microbes. The post-AXDX group had higher CCMI and PBS scores, indicating they were more ill. Despite this, the pre-AXDX group had 30.05 hours longer TTDeT, 6.17 days longer mean LOS, 5.45% more CDI, 7.12% more readmissions, and 0.26% higher mortality. The pre-AXDX group also reported adverse reactions to antibiotics, while post-AXDX did not. Our data shows AXDX use improves clinical outcomes with reduced adverse effects, mortality and CDI rate and lower costs with less LOS and readmission rates.

Disclosures
All Authors: No reported disclosures.
339. Feasibility of Heteroresistance Screening on Escherichia coli (EC) to Predict the Presence of Inner Colonies (IC) During Fosfomycin Disk Diffusion (DD) Testing
Authors: Salay Jenna , Bixby Morgan L , Hirsch Elizabeth B 
Published: December 2022

Abstract

Background
Growth of IC within the zone of inhibition during fosfomycin DD testing in EC are found, but CLSI and EUCAST interpretation criteria for IC are contradictory. There is a need to determine appropriate methods of interpretation to prevent resistant infections, thus evaluating the susceptibility of IC EC isolates in comparison to parent can help determine optimal methods for DD testing. A heteroresistance screening test has potential to identify isolates with IC. We sought to determine the feasibility of heteroresistance screening to predict the presence of IC in clinical EC isolates.

Methods
A convenience collection (n=48) of EC parent isolates underwent fosfomycin DD testing to identify those with IC. Broth microdilution (BMD) testing was performed on all parent and IC (n=34) to determine minimal inhibitory concentrations (MICs) to establish inclusion criteria for heteroresistance screening. A disk elution test for heteroresistance screening was performed in duplicate on separate days. In tubes of Mueller-Hinton broth, 6 commercial fosfomycin disks (each 200 μg fosfomycin and 50 μg glucose-6-phosphate) were eluted for 90 minutes. One hundred microliters of each bacterial isolate from an overnight culture was suspended in tubes. A positive test was a turbid tube after 72 hours of incubation.

Results
The parent isolates (n=48) had an MIC range of 1 to &gt;256 μg/mL with a median of 4 μg/mL. The subset of IC isolates (n=34) had an MIC range between ≤8 and &gt;1024 with a median of 128 μg/mL. Nineteen IC isolates met the inclusion criteria for the heteroresistance screening; 5 isolates did not produce IC (MIC range of 1-32 μg/mL) while 14 isolates produced IC (MIC range of 1-16 μg/mL). Of these 19 isolates, 6 (32%) were heteroresistant using the disk elution test. Of those with IC, 4 (29%) were heteroresistant while 2 (40%) isolates without IC were heteroresistant.

Conclusion
A heteroresistance screening test did not provide consistent data to predict the presence of IC among this EC collection. A larger isolate set and further studies are needed to understand the feasibility of a heteroresistance screening test and increased resistance in IC resulting from fosfomycin DD testing among EC.

Disclosures
Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Advisor/Consultant|MeMed: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support.