bluuebunny/crossref_metadata_2025 huggingface dataset:
286. Prevalence and Clinical Outcomes of COVID-Associated Pulmonary Fibrosis
Authors: Vogler Andrew J , Garcia Anselmo , Mafi Neema , VanDenBerg Chad M , Huang Vanthida
Published: December 2022

Background

Pulmonary fibrosis (PF) is a well-known consequence of severe lung disease and is associated with permanent changes as well as irreversible pulmonary dysfunction. The development of PF in patients infected with COVID-19 has been documented in multiple studies and case reports. However, prevalence and outcomes associated with PF have not been well established. Therefore, we sought to evaluate the prevalence and clinical outcomes of PF among patients infected with COVID-19.

Methods

This is an observational cohort study from January 2020 – January 2022. We collected data from adult patients diagnosed with COVID-19 who had at least two separate computerized tomography (CT) scans. Patients were grouped based on whether evidence of developing PF, defined by clinical radiological parameters, were seen on CT. The initial CT must be negative for PF to be included. We collected the following information: baseline characteristics, secondary infection, mortality, and treatments. The primary objective was to determine the prevalence of PF among COVID-19 patients. Secondary objectives were to evaluate the differences in 30-day all-cause mortality; intensive care unit (ICU) mortality; and prevalence of secondary infections.

Results

A total 161 patients were COVID-19 positive with multiple CT scans; 27 (16.8%) had signs of PF while 134 (83.2%) did not. Of the patients with signs of PF, 13 (48.1%) were male (mean age of 57 years) and 13 (48.1%) were admitted to the ICU. There was no difference in secondary bacterial infection between fibrotic and non-fibrotic patients (55.6% vs 38.5%, p=0.20). The most common bacterial infection among PF patients was caused by S. aureus (26.7%). The most common infection type among PF patients was nosocomial pneumonia (46.7%). Mortality at 30-day was higher in the fibrotic patients, 70% vs 24.2% (p< 0.01). The ICU mortality trended higher in the fibrotic group (69.2% vs 36.6%, p=0.124), although it was not statistically significant.

Conclusion

Pulmonary fibrosis can be fatal as a complication of COVID-19. Further investigation is warranted to evaluate the outcomes of PF in patients with COVID-19.

Disclosures

All Authors: No reported disclosures.
287. Procalcitonin and D-dimer levels at baseline, but not CRP, were informative of COVID-19 hospitalization outcomes
Authors: Mathew Trini , George Julie , Yost Christine N , Deebajah Mustafa , Johnson Paul C , Huang James , Carpenter Christopher F
Published: December 2022

Background

The WHO estimates 512 million cases of COVID-19 and 6.2 million deaths globally as of May 4th, 2022. In Michigan (MI), the first case was diagnosed March 10th, 2020. We describe here outcomes of COVID-19 patients cared for in a large tertiary hospital in 2020 spanning two surges based on baseline lab values for C-reactive protein (CRP), Procalcitonin (PC), and D-Dimer (DD).

Methods

After IRB approval, adult patients diagnosed via PCR with COVID-19 during the two surges in 2020 and admitted to Beaumont Hospital, Royal Oak, an 1,131 beds tertiary care referral center in MI, were reviewed. Demographic, clinical and laboratory characteristics were obtained from the EMR. ICD-10 classification diagnoses were utilized to identify comorbidities, and patient BMIs were based on the admission values in the EMR. Outcomes were defined as death during current admission, transfer to nursing home or other facility, or discharge home. Using a tree-based model and the combined levels of the three labs we defined a hierarchy of four lab levels, each progressively having increased risk of death. We then analyzed the outcome for the four levels, adjusting for time period (surge), age, sex, race, BMI and comorbidities. Data was analyzed using SAS statistical software version 9.4 (SAS Institute).

Results

A total of 2197 patients were identified from March through December 2020, of whom 1118 had CRP, PC and DD available at baseline. The mean age was 66.7 years (SD 16.1) for the cohort in first surge (March-June), and 66.4 (15.6) in the latter surge (July-December, Table1). More patients had a PC of >0.5 in the first surge (25.7%) than the second (13.2%). After adjusting for all other factors, the hierarchical lab levels are significantly associated with outcomes. Of note, baseline CRP value was not informative. Compared to the 2nd level (Table 2), the lowest level (PC < 0.1) has significantly lower odds of death [OR=0.37, 95% CI (0.19, 0.73)], while the highest level, (DD >1000 and PC ≥ 0.26) has significantly higher odds of death [OR=3.01, 95% CI (1.59, 5.72)].

Conclusion

Baseline PC and DD, but not CRP, were informative in determining risk of death and can assist clinicians determine possible outcomes during COVID-19 hospitalization.

Disclosures

Christopher F. Carpenter, MD, MHSA, Atox Bio: Advisor/Consultant|GSK: Advisor/Consultant|Iterum Therapeutics: Advisor/Consultant|Takeda: Advisor/Consultant.
293. Risk factors for COVID-19 associated pulmonary aspergillosis (CAPA) in severe COVID-19 and impact of airborne fungal contamination within negative pressure isolation room
Authors: Lee Jung Ah , Ahn Sanggwon , Ju Lee Se , Kim Jinnam , Lee Ki Hyun , Kim Chang Hyup , Yeom Joon-sup , Ku Nam Su , Jeong Su Jin , Kim Jung Ho , Ho Hwang Jung , Yong Dongeun , Choi Jun Yong , Ahn Jin Young
Published: December 2022

Background

COVID-19 increase the risk of invasive pulmonary aspergillosis. However, the risk factors and fungal origin of COVID-19 associated pulmonary aspergillosis (CAPA) is not fully defined yet. We aim to identify the risk factors for CAPA in severe COVID-19 and evaluate association between fungal contamination within the air of negative pressure rooms and diagnosis of CAPAs.

Methods

We performed a retrospective case-control study to identify risk factors for CAPA with 420 severe COVID-19 patients from March 2020 to January 2022 who admitted to a tertiary care hospital in South Korea. CAPA was defined with modified AspICU criteria. Control, matched by admission date and severity of COVID-19 at admission, was selected for each case. Air sampling and fungal culture was done on Jan 2022 with a microbial air sampler (MAS-100NT) at 11 spaces in the COVID-19 designated isolation ward including 9 negative pressure isolation rooms (IRs). A cross-sectional comparison between rooms with and without airborne fungal contamination was performed.

Results

A total of 420 COVID-19 patients were hospitalized during the study period, and 51 patients were diagnosed with CAPA (prevalence 12.14%, incidence 6.26 per 1000 patient•day). Multivariate analysis showed that older age (odds ratio [OR] 1.051, 95% confidence intervals [CI] 1.006-1.009, p=0.025), mechanical ventilator use (OR 2.692, 95% CI 1.049-6.911, p=0.04), and lymphopenia (OR 4.353, 95% CI 1.727-10.975, p=0.02) were independent risk factors for CAPA. (Table 1, 2) Aspergillus spp. was identified within the air from 7 out of 11 spaces including 6 IRs and 1 doctors’ room. (Figure 1). All 6 IRs with positive aspergillus culture were being occupied by patients at least 8 days. Among 6 patients, 3 had already been diagnosed with CAPA whereas the other 3 were not diagnosed with CAPA through the observation period. Among 4 patients in isolation rooms without airborne aspergillus contamination, one patient had been diagnosed as CAPA before air sampling. (Table 3).

Conclusion

Association between CAPA and airborne aspergillus contamination within the negative pressure room could not be demonstrated in this study. Rather than environmental factors, patient factors such as older age, ventilator care, and lymphopenia were found to be associated with CAPA diagnosis.

Disclosures

All Authors: No reported disclosures.
295. SARS-CoV-2 Associated Multisystem Inflammatory Syndrome in Adults (MIS-A): a Multicenter Case Series.
Authors: Trigueros Ricardo , Denmeade Travis , Pannebaker Danielle , Maves Ryan C
Published: December 2022

Background

MIS-A frequently presents with symptoms including fevers, cardiovascular, gastrointestinal mucocutaneous, and neurologic involvement in both children and adults. Predominantly occurs in previously healthy children and young adults, disproportionately affecting individuals of African,Latino and Asian descent. Represents one of the most significant and yet under-recognized clinical consequences of SARS-CoV-2 infection.

Methods

A retrospective review was performed of the identified MIS-A cases admitted to two institutions between January 2020-December 2021. Included cases required evidence of present or previous SARS-CoV-2 infection by either PCR or antigen testing; and meeting the CDC definition for MIS-A. After case identification, we collected clinical and laboratory data to analyze demographics, clinical symptoms, laboratory result, imaging, length of hospitalization and therapeutic interventions.

Results

Ten cases were identified in the established period of time. The average interval to hospital admission was 31days. Clinical symptoms included fever, malaise, gastrointestinal complaints, dyspnea, diffuse rash. Males outnumbered females in a ratio of 7:3,with African American and Latino patients comprising 80% of the cases. All patients had elevated inflammatory markers and the most commonly manifesting organ dysfunction was cardiovascular system.

Conclusion

This case series helps reinforce the characterization of an as yet incompletely understood and challenging clinical syndrome, providing insight to guide diagnosis and treatment of MIS-A. A greater understanding of MIS-A may facilitate earlier syndromic recognition in order to improve outcomes, reduce unnecessary antimicrobial use, and reduce costs.

Disclosures

Ryan C. Maves, MD, AiCuris: Grant/Research Support|Sound Pharmaceuticals: Grant/Research Support|Trauma Insights, LLC: Advisor/Consultant.
296. SARS-CoV-2 Illness Severity and Early Hospitalization Outcomes in a Multicenter Prospective Cohort Study Among Veterans
Authors: Ross Jennifer M , Sugimoto Jonathan D , Timmons Andrew , Moore Kathryn , Adams Jonathan , Wilson Deanna , Liu Cindy H , Deardoff Katrina V , Korpak Anna , Chang Kyong-Mi , Cho Kelly , Crothers Kristina , Gaziano Michael , Holodniy Mark , Hunt Christine M , Isaacs Stuart N , Jones Barbara E , Le Elizabeth , Shah Javeed , Smith Nicholas L , Lee Jennifer S
Published: December 2022

Background

Over 600,000 SARS-CoV-2 infections and 20,000 deaths have occurred among users of the Veterans Health Administration, the US’s largest integrated health care system. We explored early outcomes of SARS-COV-2 infection in Veterans.

Methods

An ongoing, prospective longitudinal cohort study of Veterans ages ≥ 18 enrolled 1,826 participants (29.0% inpatient; 49.1% vaccinated; 68.3% SARS-CoV-2-positive; 85.0% male, mean age = 57.1 years) seeking inpatient or outpatient care after SARS-CoV-2 testing at 15 Department of Veterans Affairs medical centers in July 2020 to February 13, 2022. Using multivariable regression, we estimated relationships of baseline demographic characteristics, COVID-19 vaccination, and clinical history to illness severity and cumulative length of hospital stay within 60 days of study entry. Illness severity was defined by a Veterans Affairs adaptation of the WHO COVID-19 severity scale and included 4 levels (mild, moderate, severe, or death). We derived the Charlson co-morbidity index (CCI) and other baseline characteristics from electronic health data and study questionnaires, and reported qualitative SARS-CoV-2 IgG responses using inpatients’ study-collected blood specimens.

Results

High CCI scores (≥ 5) occurred in 47 (42.7%) vaccinated SARS-CoV-2-positive inpatients and 47 (21.2%) unvaccinated. Severe illness occurred in 17 (15.5%) vaccinated inpatients, 37 (16.7%) unvaccinated inpatients, 4 (0.9%) vaccinated outpatients, and 3 (0.7%) unvaccinated outpatients. Eleven (10%) of 110 vaccinated SARS-CoV-2-positive inpatients died, as did 15 (6.8%) of the 222 unvaccinated. In SARS-CoV-2-positive inpatients, a one-step higher CCI was associated with more severe illness (aOR 1.10, 95% CI 1.01-1.20) and more hospitalization days (aIRR 1.06, 95% CI 1.03-1.10), adjusting for vaccination status. Respectively, 93% of vaccinated and 63% of unvaccinated SARS-CoV-2 positive inpatients with baseline antibody results had an anti-spike IgG response.

Conclusion

In an ongoing longitudinal cohort study of COVID-19 in US Veterans, comorbidity burden was higher among vaccinated than unvaccinated inpatients and was associated with more severe illness and hospitalization days, independent of vaccination status.

Disclosures

Christine M. Hunt, MD, MPH, Adaptive Phage Therapeutics: Advisor/Consultant|Akebia: Advisor/Consultant|Galmed: Advisor/Consultant|Otsuka: Advisor/Consultant|Palladio: Advisor/Consultant.
299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome
Authors: Zheng Hong , Yonker Lael , Donado Michele , Solomon Ben , Boribong Brittany , Gernez Yael , Maecker Holden , Sigal Natalia , Kinane Bernard , Arvin Ann , Khatri Purvesh , Weinacht Katja
Published: December 2022

Background

Multisystem inflammatory syndrome in children (MIS-C) is a severe post-infectious complication occurring weeks after SARS-CoV-2 infection. The exact mechanisms leading to immune dysregulation and organ damage remain incompletely understood. Progress in understanding the immunopathology underlying MIS-C has been halted by limited availability of pre-treatment patient samples and confounding effects of immunomodulatory treatment on previously studied specimens.

Methods

In this study, we have restricted enrollment to treatment-naïve patients with MIS-C and used a systems biology approach combining CyTOF, single cell transcriptomics, serum cytokine profiling and T cell receptor sequencing to dissect how immune responses in children with MIS-C differ from children with mild SARS-CoV2 infection, adults with severe COVID-19 and healthy individuals. We also integrated single cell transcriptomics datasets from post-treatment MIS-C samples to study how immune responses change along disease course.

Results

We identified increased activation markers and antigen presentation across multiple immune cell types in MIS-C patients from both CyTOF and single cell transcriptomics data. Importantly, in PBMCs of MIS-C patients, we identified a distinct subset of proinflammatory monocytes, with increased expression of interferon gamma response genes combined with a signature of enhanced complement expression, antigen processing and presentation, which was not observed in post-treatment MIS-C samples. Interestingly, this monocyte population bears resemblance to a subset of monocytes that emerges after the BNT162b2 mRNA vaccine booster. In addition, in PBMCs of MIS-C patients, we identify increased proportion of proliferating T/NK cells, suggesting distinct T cell expansions in MIS-C. T and NK cells in MIS-C samples also showed increased cell cytotoxicity markers.

Conclusion

Taken together, treatment-naïve MIS-C samples display distinct monocyte clusters, activated antigen presentation and complement expression, and increased T and NK cell cytotoxicity, which may account for the clinical presentation of MIS-C.

Disclosures

Purvesh Khatri, PhD, Cepheid, Inc.: Advisor/Consultant|Inflammatix, Inc.: Advisor/Consultant|Inflammatix, Inc.: Inflammatix is in negotiations to license the 9-gene signature discussed here.|Inflammatix, Inc.: Stocks/Bonds.
300. Trends in electrocardiographic and cardiovascular manifestations of patients hospitalized with COVID-19
Authors: Ngiam Jinghao Nicholas , Goh Wilson , Sim Meng Ying , Chhabra Srishti , Liong Tze Sian , Chew Nicholas W S , Chai Ping , Yeo Tiong Cheng , Cross Gail Brenda , Tambyah Paul Anantharajah , Sia Ching Hui
Published: December 2022

Background

Early in the coronavirus disease 2019 (COVID-19) pandemic, a low incidence of cardiovascular complications was reported amongst hospitalised patients with COVID-19 in Singapore. Little was known about the trend of cardiovascular complications as the pandemic progressed. As such, we sought to examine the evolving trends in electrocardiographic and cardiovascular manifestations in patients hospitalised for COVID-19 infection.

Methods

We examined the first 1781 consecutive hospitalised patients with polymerase chain reaction (PCR) confirmed COVID-19 in a tertiary academic centre. We divided the population based on those who had an abnormal electrocardiogram (ECG) and those who had a normal ECG, comparing the baseline characteristics and outcomes between the 2 groups. Cardiovascular complications such as acute myocardial infarction, stroke, pulmonary embolism, myocarditis and mortality were also examined over time.

Results

Of the 261 (14.7%) patients presenting with abnormal ECG, they were more likely to be symptomatic with complaints of breathlessness, palpitations and chest pain. Sinus tachycardia was the most common arrhythmia. Troponin I levels (41.6±264.3 vs 97.0±482.9, p=0.047) and C-reactive protein levels (20.1±50.7 vs 13.9±24.1 µmol/L, p=0.003) were significantly higher amongst those with abnormal ECGs at presentation, with a higher prevalence of myocarditis (1.9% vs 0.5%, p=0.021), pulmonary embolism (1.9% vs 0.3%, p=0.009) and acute myocardial infarction (1.1% vs 0.1%, p=0.025). Over time, there was a trend towards a higher proportion of hospitalised patients with cardiovascular complications.

Baseline characteristics of hospitalised patients with COVID-19, with or without abnormal ECG at presentation

Changes in percentage of hospitalised patients with COVID-19, experiencing cardiovascular events (acute myocardial infarction, stroke, myocarditis, pulmonary embolism and death) over time

Conclusion

A baseline ECG at presentation is a simple test that provides valuable information on potential cardiovascular complications in the context of COVID-19. Although the prevalence of abnormal ECGs is relatively low, it appears to be increasing over time amongst hospitalised patients with COVID-19.

Disclosures

All Authors: No reported disclosures.
301. Use of a multiplex PCR assay for detection of respiratory co-infections in COVID-19 hospitalized non-ICU patients: an ace up a clinician’s sleeve
Authors: Louka Christina , Velentza Lemonia , Rekleiti Nektaria , Apanomeritaki Anastasia , Mamali Vasiliki , Stamati Alexandra , Linardaki Garifallia , Gerakari Styliani , Digalaki Katina , Giannitsioti Efthymia , Chrysos Georgios , Zarkotou Olympia
Published: December 2022

Background

Bacterial co-infections in COVID-19 patients represent a significant challenge for clinicians and can impact outcomes. Rapid identification of bacterial co-pathogens improves management, and is crucial to avoid inappropriately administered antimicrobials. We evaluated the use of a multiplex PCR assay in the early detection of respiratory co-infections in COVID-19 hospitalized patients.

Methods

The study included non-ICU patients with high clinical suspicion of respiratory co-infection. Lower respiratory tract samples (sputum/bronchial secretions), were analyzed using BIOFIRE® FILMARRAY® pneumonia panel plus [(bioMerieux, USA), FA]. Specimens were considered as acceptable based on Gram stain. Conventional cultures were also performed.

Results

A total of 28 samples from 27 patients (20 males, median age 60 years, IQR 49-71) were analyzed. 8/27 patients were intubated, 5 were treated with high flow nasal canula oxygenation and 11 with high or low oxygen mask. 18 patients received dexamethasone. Co-infection was detected in 17/27 patients (62.9%). 11 specimens were collected in less than 48 hours from admission and no target was identified in 6/11. Detected pathogens and AMR genes, per sample tested, are presented in the table. Bacterial pathogens and any AMR genes were detected in 15 and 4 samples, respectively, leading to modifications of antimicrobial treatment. The semi-quantitative results along with patients’ clinical presentation assisted with differentiation of bacterial colonization versus infection, especially in cases where multiple targets were identified. De-escalation was implemented for 12 patients, for whom no co-infection or a viral co-pathogen (n=2) was detected. One patient was co-infected with another Coronavirus; further analysis, using the FA respiratory panel, detected Human coronavirus HKU-1 along with SARS-CoV-2. Median time until discharge or death was 13.5 days (IQR 9-24). Overall mortality was 33.3%.

Detected pathogens, microbial load and AMR genes, per sample tested.

Conclusion

Implementation of FA assay proved effective for the rapid detection of respiratory co-infections in COVID-19 non-ICU patients. Molecular panel-based assays can contribute to timely adaptation of antimicrobial treatment, benefiting patient management and antibiotic stewardship strategies.

Disclosures

All Authors: No reported disclosures.
302. Using Severe Acute Respiratory Syndrome Coronavirus-2 Spike Protein Antibody Serology in addition to the ISARIC 4C Risk Score to Better Discriminate Adverse Clinical Outcomes in Hospitalized Patients with Coronavirus Disease 2019.
Authors: Goh Wilson , Nicholas Ngiam Jinghao , Chhabra Srishti , Sim Meng Ying , Tambyah Paul Anantharajah , Cross Gail Brenda , Chew Nicholas W S , Sia Ching Hui
Published: December 2022

Background

The Coronavirus disease 2019 (COVID-19) pandemic continues to threaten many countries globally. Large-scale vaccination exercises have helped to reduce transmission and severity of disease. We sought to modify an existing clinical score (the ISARIC-4C mortality score) to include serological status to better prognosticate hospitalized patients with COVID-19.

Methods

We examined the first 1781 consecutive hospitalized patients with polymerase chain reaction (PCR) confirmed COVID-19 in a tertiary academic centre. We divided the study population into those requiring intensive care and those who did not require throughout their inpatient stay. Baseline characteristics examined include medical comorbidities, vaccination status, SARS-CoV-2 serology spike protein, duration of fever and haemodynamics were compared. Adverse outcomes were defined as patients who required intensive care or mortality. Performance of the risk scores were measured by the area under receiver operating characteristic curves (AUC) in predicting adverse outcomes.

Results

The 55 patients requiring intensive care during their inpatient stay tended to have persistent fever beyond 72 hours and had lower titres of spike protein antibodies. (58.9 (±105.3) U/mL vs 144.2 (±116.2) U/mL, p = 0.007). A high spike protein antibody titre >75 U/mL was independently protective for adverse outcomes (adjusted OR 0.15, 95% CI 0.04-0.53), even after adjusting for the ISARIC-4C score and the presence of persistent fever. Adding the serological status and presence of persistent fever to the ISARIC-4C score improved its performance in predicting adverse outcomes (AUC 0.84, 95% CI 0.78-0.89).

Conclusion

Addition of the SARS-CoV-2 serology spike protein titre and prolonged fever to the ISARIC-4C mortality score helps to better prognosticate adverse clinical outcomes in hospitalized patients with COVID-19.

Disclosures

All Authors: No reported disclosures.
311. Modeling Diagnostic Testing Strategies for SARS-CoV-2 to Minimize Societal Costs and Return People to Work
Authors: Zavala Sofia , Cox Gary M , Belknap Robert W , Smith Becky A , Lewis Sarah S , Polage Christopher R , Turner Nicholas A , Stout Jason E
Published: December 2022

Background

The shift to more transmissible but less virulent strains of SARS-CoV-2 has altered the risk calculation for infection. Particularly among young adults, the economic burden of lost work due to isolation exceeds the economic burden of morbidity due to infection. Testing strategies must adapt to these changing circumstances.

Methods

We modeled six testing strategies to estimate total societal costs for symptomatic people 18-49 years old: isolation of all individuals with no testing, rapid antigen test (RAg), RAg followed by a second RAg 48h later if first negative, RAg followed by a polymerase chain reaction (PCR) if negative, RAg followed by a PCR if positive, and PCR alone. We calculated costs for hypothetical cohorts of 100 symptomatic healthcare workers tested with each strategy; we included testing costs, lost wages, and hospitalization costs for the index, secondary, and tertiary cases. Key assumptions were 5% prevalence of infection, sensitivity of first/second RAg 40/80% with 97% specificity, PCR sensitivity/specificity 95/99%, all individuals isolate at symptom onset, are tested the same day, and isolate for 5 days if positive. RAg results were available the same day, PCR results were available the next day (Figure 1). One-way sensitivity analyses were performed for RAg sensitivity (20-80%) and positivity rate (1-80%).

Results

The least expensive strategy was RAg alone (Figure 2). This was primarily driven by its low sensitivity, which reduced lost wages at the expense of missing cases. At a threshold for RAg sensitivity lower than 29%, PCR testing alone became the cheapest strategy. When the positivity rate was > 6% confirming a negative RAg with a PCR became the cheapest strategy, closely followed by PCR alone. At a positivity rate of > 29%, isolation without testing was cheapest followed by confirming a negative RAg with a PCR and by the serial RAg test strategies (Figure 3).

Conclusion

In relatively young, healthy populations, a single rapid test was the least expensive strategy when the positivity rate was < 6%, testing that included PCR became cheapest at intermediate positivity, and empiric isolation was cheapest at positivity > 29%. Calibrating SARS-CoV-2 test strategies based on epidemiology may save societal costs.

Disclosures

Nicholas A. Turner, MD, MHSc, Aperio: Advisor/Consultant.
317. Use cases for rapid antigen-detecting tests for COVID-19 screening and surveillance: a systematic review
Authors: Anand Apoorva , Bigio Jacob , MacLean Emily , Underwood Talya , Pai Nitika Pant , Carmona Sergio , Schumacher Samuel G , Toporowski Amy
Published: December 2022

Background

Testing remains critical to controlling the COVID-19 pandemic. Antigen-detecting rapid diagnostic tests (Ag-RDTs), which can be used at the point of care, have the potential to increase access to COVID-19 testing, particularly in settings with limited laboratory capacity. This systematic review synthesized literature on specific use cases and performance of Ag-RDTs for detecting SARS-CoV-2, for the first comprehensive assessment of Ag-RDT use in real-world settings.

Methods

We searched three databases (PubMed, EMBASE and medRxiv) up to 12 April 2021 for publications on Ag-RDT use for large-scale screening and surveillance of COVID-19, excluding studies of only presumptive COVID-19 patients. We tabulated data on the study setting, populations, type of test, diagnostic performance, and operational findings. We assessed risk of bias using QUADAS-2 and an adapted tool for prevalence studies.

Results

From 4313 citations, 39 studies conducted in asymptomatic and symptomatic individuals were included. Of 39 studies, 37 (94.9%) investigated lateral flow Ag-RDTs and 2 (5.1%) investigated multiplex sandwich chemiluminescent enzyme immunoassay Ag-RDTs. Six categories of testing initiatives were identified: mass screening (n=13), targeted screening (n=11), healthcare entry testing (n=6), at-home testing (n=4), surveillance (n=4) and prevalence survey (n=1). Sensitivity and specificity values by testing category are shown in the table. Ag-RDTs were noted as convenient, easy-to-use, and low cost, with a rapid turnaround time and high user acceptability. Risk of bias was generally low or unclear across studies.

Conclusion

During the first year of the COVID-19 pandemic, Ag-RDTs were used across a wide range of real-world settings for screening and surveillance of COVID-19 in both symptomatic and asymptomatic individuals. Ag-RDTs were fast and simple to run, but due to their often low sensitivity, careful consideration must be given to their implementation and interpretation. Ag-RDTs have subsequently been rolled out more broadly and recommended for COVID-19 self-testing.

Disclosures

Talya Underwood, MPhil, Oncotherapeutics: Medical writing.
318. A Pain in the Neck: Cervical Pyomyositis, a Rare Case of Extraintestinal Nontyphoidal Salmonellosis Further Characterized by Whole-Genome Sequencing.
Authors: Haroun Pishoy , Yang Shangxin , Adamson Paul C , Sakona Ashlyn N
Published: December 2022

Background

Nontyphoidal salmonellosis (NTS) is the second-most common foodborne illness in the US, but extraintestinal manifestations are rare. We describe a case of sternocleidomastoid (SCM) pyomyositis, a rare entity, caused by Salmonella enterica, further delineated by whole-genome sequencing (WGS).

A 55 year old male with liver cirrhosis and uncontrolled type-II diabetes mellitus presented with a six-day history of an enlarging left-sided neck mass. He had no fevers, chills, night sweats, nausea, vomiting or diarrhea. He had recently returned from Saudia Arabia with exposures to camels, bats and lemurs. He did not consume raw foods or dairy products.

Physical exam revealed normal vital signs and a large firm neck mass. Labs were notable for leukocytosis and hyperglycemia. Neck computed tomography revealed a 6 cm heterogeneous mass inseparable from the left SCM. He required repeated drainage procedures; histopathology revealed skeletal muscle with inflammation, but no malignancy. Blood and procedural cultures grew Salmonella group B. He was treated with ceftriaxone then trimethoprim-sulfamethoxazole. Follow-up 4 weeks after presentation revealed only residual induration.

Methods

WGS was performed using Illumina MiSeq. Genotype and antimicrobial resistance markers were identified using MLST, KmerFinder and ResFinder on Center of Genomic Epidemiology. Virulence factors were identified using VFanalyzer.

Results

The bacteria was identified as Salmonella enterica subspecies enterica serovar Typhimurium and typed as ST19, the major phylogroup of Typhimurium globally. Characteristics associated with invasive NTS (iNTS) identified by WGS included genes encoding Type III secretion system and Invasin A. Other virulence factors included fimbrial adherence determinants, macrophage inducible genes, and an intracellular toxin SpvB. Resistance genes included aac(6')-Iaa, which confers resistance to tobramycin and amikacin, and qnrB19, which predicts resistance to ciprofloxacin. However, no quinolone resistance-related mutations were detected in gyrA, gyrB, parC and parE genes.

AMR Genes

Antimicrobial resistance genes identified by whole-genome sequencing of the Salmonella isolate.

Conclusion

Patients with uncontrolled diabetes are at increased risk of iNTS with or without associated diarrhea. WGS can identify additional factors that may influence morbidity and resistance.

Disclosures

All Authors: No reported disclosures.
319. Clinical accuracy and utility of plasma microbial cell free DNA NGS for the diagnosis of invasive aspergillosis in patients with hematologic malignancy and COVID-19
Authors: Lee Ki Hyun , Yeom Joon-sup , Choi Jun Yong , Ku Nam Su , Jeong Su Jin , Kim Jung Ho , Ju Lee Se , Kim Jinnam , Kim Chang Hyup , Lee Jung Ah , Jang Ji Eun , Won Dongju , Shin Saeam , Lee Seung-Tae , Ahn Jin Young
Published: December 2022

Background

Invasive aspergillosis (IA) is a great threat to the severely immunocompromised and patients with coronavirus disease (COVID-19). However, diagnosis of IA is often difficult due to need for invasive biopsy and low sensitivity of other diagnostic tests. Next-generation sequencing (NGS) of plasma cell free DNA (cfDNA) can be a novel non-invasive diagnostic modality. We evaluated the clinical accuracy and utility of microbial cfDNA NGS for the diagnosis of IA in patients with hematologic malignancy (HM) and COVID-19.

Methods

A single-center prospective study of plasma microbial cfDNA NGS was conducted in a tertiary-care hospital in South Korea. We enrolled adult patients with HM and COVID-19, who suspected IA and performed conventional diagnostic tests for IA. The results of NGS were compared with the diagnosis of IA through conventional methods. IA cases were diagnosed according to EORTC/MSG definitions in patients with HM, and modified AspICU criteria in patients with COVID-19. (Figure 1). Figure 1.Flow chart for the participant selection method used in this study

Results

Between March 2021 and January 2022, a total of 33 participants (22 [64.7%] male, median age 66.0 [50.5, 72.0]) were enrolled;19 participants with HM and 15 with COVID-19 were analyzed (Figure1 and Table1). In participants with HM, aspergillus cfDNA was detected in 100% of both proven (1/1) and probable (12/12) IA cases, and 33.3% of both possible (1/3) and no IA (1/3) cases. In participants with COVID-19, 46.2% of probable IA (6/13) showed positive aspergillus cfDNA. Detection rate of aspergillus cfDNA was significantly higher in proven/probable IA cases in participants with HM compared to participants with COVID-19. (100% vs 46.2%, p=0.005) (Figure 2). As shown in Table 2, among proven/probable IA cases, participants with positive aspergillus cfDNA showed significantly higher rate of having uncontrolled hematologic disease, receiving stem cell transplantation and recent chemotherapy. In three participants with HM, non-aspergillus strains confirmed by cfDNA NGS were in accordance with pathogens identified through conventional culture methods. Table 1.Baseline characteristics of participants suspected of invaisve aspergillosis performing microbial cell free DNA NGSFigure 2.cfDNA detection rate in participants with suspected fungal infection according to the EORTC/MSG or modified AspICU diagnostic criteria

Conclusion

Detection of aspergillus cfDNA showed high concordance in the results of conventional diagnostic methods in proven/probable IA of patients with HM and could be a helpful non-invasive approach to IA diagnosis in those populations.

Disclosures

All Authors: No reported disclosures.
327. Understanding Current Clinical Scenarios for Plasma Microbial Cell-free DNA Diagnostic Testing toward Informing Diagnostic Stewardship
Authors: Lau Constance , Matthew Hill T , Messacar Kevin , Nolte Frederick S , Park Sarah Y
Published: December 2022

Background

Plasma microbial cell-free (mcfDNA) testing has emerged as a promising tool for unbiased detection of pathogens in patients with suspected infections. A systematic evaluation of the patient populations in which this test is used may provide insight into applications for clinical use. We describe demographic and clinical characteristics of patients tested with plasma mcfDNA linked to the Premier Healthcare Database (PHD).

Methods

A retrospective cross-sectional analysis was conducted using the PHD: a US hospital-based, service-level, all-payer database containing information primarily from geographically diverse communities, teaching hospitals, and health systems. Patients with plasma mcfDNA testing 4/1/2018-12/31/2020 were deterministically linked to the PHD. Patient characteristics were collected via chargemaster data, ICD-10 diagnosis, and procedure codes. Immunocompromised (IC) status was identified using 2021 Agency for Healthcare Research (AHRQ) ICD-based definitions. The AHRQ Elixhauser Comorbidity Index score was derived using ICD-10 codes to indicate comorbidity burden.

Results

A total of 778 patients in the PHD underwent plasma mcfDNA testing during the study period, 88% of whom were tested in the inpatient setting (Table 1). Thirteen percent had a discharge diagnosis of sepsis with an unspecified organism. Median inpatient length of stay was 10 days with a median of 4 days from time of admission to plasma mcfDNA testing. Forty-seven percent of patients were IC with a majority (62%) having an Elixhauser score ≥ 7, suggestive of a high comorbidity burden (Table 2). Two hundred forty-nine (32%) inpatients required intensive care unit (ICU) level care for a median 15 days.

Conclusion

Plasma mcfDNA testing is primarily being used in the inpatient setting in a wide variety of clinical scenarios, particularly among seriously ill and immunocompromised patients, who tend to have broad infectious disease differentials and high morbidity and mortality risks. Understanding the current populations, indications, and timing of mcfDNA testing may contribute to developing diagnostic stewardship research and guidelines to optimize impact on clinical outcomes.

Disclosures

Constance Lau, MPH, Karius, Inc.: Current employee|Karius, Inc.: Stocks/Bonds T. Matthew Hill, PharmD, PhD, Karius, Inc: Paid employee|Karius, Inc: Stocks/Bonds Frederick S. Nolte, PhD, D(ABMM), F(AAM), Karius: Employee.
329. Bedside Inoculation of Blood Culture Bottles Does Not Improve Ascites Culture Positivity Rate in Spontaneous Bacterial Peritonitis
Authors: Brehm Tyler , Al Mohajer Mayar , Lasco Todd M
Published: December 2022

Background

Prior research demonstrates increased positivity rate for ascites cultures in spontaneous bacterial peritonitis (SBP) when directly inoculated into blood culture bottles at bedside, versus the “conventional method” - transportation of ascitic fluid in a sealed syringe to the laboratory, centrifuging, and plating on Chocolate, Blood, and MacConkey’s agars and in a Schaedler broth. We hypothesized that collection of ascites via direct inoculation into blood culture bottles would improve ascites culture positivity rate in SBP when compared to prior methods.

Methods

In November of 2021, our institution implemented a policy in which all ascites cultures were directly inoculated into blood culture bottles at bedside. We retrospectively reviewed all ascites cultures collected from May of 2021 through April of 2022, including all cultures with an absolute neutrophil count of greater than 250 cells/mm3. We excluded all samples from patients with secondary bacterial peritonitis and all samples collected in November. If a patient had multiple samples that met inclusion criteria, only the first was included for analysis. Our primary outcome was positivity rate of cultures pre- and post-implementation of this new policy.

Results

1375 ascites cultures were collected. Of these, 52 met our inclusion criteria. These patients were on average 58 years old (range 33-74), 50% female, with a median MELD of 25.5 (range 8-40). The conventional method was positive in 7/37 (18.9%) cultures, and direct inoculation of blood cultures in 1/15 (6.67%), p = .27.

Conclusion

As opposed to the previous literature, we detected no difference in positivity rate between the conventional method of ascites culture compared to direct inoculation of blood cultures at the bedside. This difference from prior literature may be due to differences in time to inoculation, our smaller sample size, or overfilling of the bottles during inoculation.

Disclosures

All Authors: No reported disclosures.
332. Broad range PCR of pleural fluid improves diagnosis of bacterial pneumonia complicated by parapneumonic effusion
Authors: Upadhyayula Shankar
Published: December 2022

Background

Bacterial pneumonia complicated by a para pneumonic effusion is frequently encountered in hospitalized patients. However, identifying the etiology of pneumonia remains elusive. Published data report rates of bacteremia ranging from 13-26% among patients with pneumonia complicated by parapneumonic effusion. Good quality sputum samples are difficult to obtain in children. Culture of pleural fluid is helpful, but most patients are already pretreated before a specimen is obtained limiting utility. Nucleic acid assays of pleural fluid have reported sensitivities from 40-80%. We wanted to review our experience with pleural fluid nucleic acid assay at Akron childrens hospital

Methods

Using help from our laboratory data support team, we retrospectively reviewed the records of all pleural fluid isolates that were sent out to Washington University Medical Center for 16 S rRNA sequencing (broad range polymerase chain reaction assay). The review covered a 8-year time period ranging from January 2014 to March 2022. Negative blood and pleural fluid cultures were a prerequisite before the send out for nucleic acid assay.

Results

A total of 29 pleural fluid samples were sent out for 16S rRNA sequencing. 22 of these had a detectable target. This translated into a yield of about 75%. The following table summarizes our findings.

Conclusion

In our experience, nucleic acid assay of the pleural fluid is valuable in making a bacteriological diagnosis of pneumonia with para pneumonic effusion. Its benefit remains in patients pretreated with antibiotics. For the individual patient it may help narrow antibiotic therapy. At an institutional level it would allow for developing guidelines for empiric antibiotic management. However, in most institutions’ nucleic acid assay of pleural fluid remains a send out test and optimizing workflows to reduce turnaround time remains a challenge.

Disclosures

All Authors: No reported disclosures.
333. Clinical Impact of a Multiplex Rapid Diagnostic Panel in Critically Ill Patients
Authors: Esplund Jayda , Taylor Alex D , Stone Tyler , Palavecino Elizabeth , Kilic Abdullah , Luther Vera , Beardsley James
Published: December 2022

Background

The BioFire FilmArray® Pneumonia Panel® (PP) is a rapid diagnostic test that detects select bacterial and viral respiratory pathogens and the presence of certain antimicrobial resistance genes within 75 min of testing. Starting Nov 2021 respiratory specimens from all adult ICU patients (pts) with quantitative cultures (cx) obtained by bronchoalveolar lavage (BAL) or tracheal aspirate (TA) were automatically tested with PP. The purpose of this study was to evaluate the clinical impact of the PP.

Methods

This single-center, retrospective cohort study compared patients prior to (PRE) (Jan - Mar 2021) and after (POST) (Jan - Mar 2022) implementation of the PP. Adult ICU pts with a quantitative cx obtained by BAL or TA during the study periods were reviewed in random order until 25 pts from each study month meeting study criteria were identified (75 pts in each cohort). Pts with another infection other than bacteremia with the same causative pathogen requiring antibiotics (ABX) in the previous 14 days through 5 days after specimen collection or pts who died within 5 days after specimen collection were excluded. ABX therapy for the 5 days after cx collection was evaluated. The primary outcome was time to first ABX change based on microbiologic test results. Secondary outcomes included ABX days of therapy (DOTs), time to adequate therapy, and potential vs actual ABX changes made based on the PP in POST cohort.

Results

PRE pts were a median of 54 yrs old and 56% female compared to 59 yrs and 32% female in POST cohort. Median time to first ABX change based on microbiologic data was 50.3 hrs PRE vs 21.2 hrs POST (p=0.0006). 56 (75%) of POST ABX regimens were eligible for change based on PP results; actual change occurred in 30 (54%) of these regimens (ABX de-escalation in 23 and escalation in 7). Median ABX DOTs were 8 PRE vs 6 POST (p = 0.07). For the pts with ABX changes made based on PP results, median time to first ABX change was 10 hrs. For pts who were initially on inadequate therapy, time to adequate therapy was 67 hrs PRE vs 37 hrs POST.

Conclusion

The PP was associated with decreased time to first ABX change and fewer ABX DOTs. The PP may have had a larger impact if a higher percentage of potential ABX changes were implemented. The PP may be a useful ABX stewardship tool.

Disclosures

All Authors: No reported disclosures.
335. Comparison of inner colony production among Escherichia coli (EC) and Klebsiella pneumoniae (KP) during fosfomycin disk diffusion (DD) testing
Authors: Bixby Morgan L , Salay Jenna , Hirsch Elizabeth B
Published: December 2022

Background

Recent studies have indicated the presence of IC arising within the zone of inhibition during fosfomycin DD testing. CLSI and EUCAST have contradicting recommendations for interpreting these IC; CLSI recommends considering the presence of IC when interpreting DD results while EUCAST recommends ignoring them. Although DD testing is approved only for use with EC per both organizations, it is often used for testing of non-EC organisms despite neither organization publishing non-EC Enterobacterales breakpoints (BP). We sought to compare the rates of IC production among EC and KP isolates in order to assess the applicability of fosfomycin DD for KP isolates.

Methods

A convenience sample of 128 (80 KP and 48 EC) clinical isolates with varied phenotypic profiles from 3 United States locations were included. Of these, 26% (n = 21) of KP and 29% (n =14) of EC displayed ESBL phenotypes and 19% (n = 15) of the KP were KPC producing. Fosfomycin susceptibility testing via DD was conducted in duplicate on separate days following interpretations recommended by each organization. Isolates were considered IC-producing if at least 5 IC arose during ≥ 1 replicate of DD testing.

Results

Overall, 61% (n = 78) of isolates produced IC including 75% (n = 36) of EC and 52.5% (n = 42) of KP (Table 1). Of the EC isolates that produced IC, 89% (n = 33) were susceptible per CLSI and 92% (n = 34) were susceptible per both EUCAST oral and IV BP. In contrast, only 41% (n = 17) of KP isolates with IC were susceptible per CLSI and 2% (n = 1) were susceptible per both EUCAST BP. The presence of IC did not result in significant differences of zone diameters (1-14mm, EC; 2-13mm, KP) when comparing organization procedures. Table 1.Production of IC by susceptibility categorization based on three sets of fosfomycin BP

This table compares the KP and EC collection based on three different breakpoints (CLSI, EUCAST oral, and EUCAST IV) using the entire collection and the subset that produced IC (EC: 36/48 and KP: 42/80).

Conclusion

The BP and IC interpretations from EUCAST and CLSI categorized most EC isolates, including those that produced IC, as susceptible. EUCAST’s larger zone measurements and ignoring IC produced near identical results to CLSI. EUCAST’s lower BP categorized very few KP as susceptible even when ignoring the presence of IC. CLSI BP captures a more diverse categorization of susceptibility of KP isolates consistent with the diversity of zone measurements. These findings warrant further investigation into the clinical relevance of IC and applicability of fosfomycin DD BP in KP.

Disclosures

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