bluuebunny/crossref_metadata_2025_split huggingface dataset:
458. Risk of COVID-19 and vaccine immunogenicity in pediatric solid organ transplant recipients – a single center study in South Korea
Authors: Baek Jee Yeon , Ihn Kyoung , Koh Hong , Lee Keum Hwa , Kim Min Young , Kim Sinyoung , Kang Ji-Man , Choi Jun Yong , Park Younhee , Kim Myoung Soo 
Published: November 2023

Abstract

Background
Solid organ transplant (SOT) recipients are at high risk for severe COVID-19 due to immunosuppressant (IS) use. Compared to adult SOT recipients (SOTRs), studies on risk and vaccination effectiveness in pediatric SOTRs are limited. We aim to investigate the epidemiologic characteristics of COVID-19 and vaccine immunogenicity in pediatric SOTRs.

Methods
This study was conducted at Severance Hospital in Korea, between 1999-2022. All SOTRs received SOT at the age ≤ 18 years were included. SOTRs who had a history of COVID-19 before SOT were excluded. Severe case was defined when there’s oxygen demand. Demographic data and information for risk factor exploration were retrospectively collected through chart review. Blood samples were collected prospectively after the COVID-19 vaccination policy for children was implemented. Humoral immunogenicity to WT, Delta and Omicron was investigated after 2 doses of BNT162b2 (BNT) using SARS-CoV-2 anti-S IgG titers, surrogate neutralization inhibition and plaque reduction neutralization tests. Post-vaccination samples of adult SOTRs were used as controls.

Results
A total of 118 SOTRs were included. The median age at SOT was 5 years (1-11 years), and the male to female ratio was 1:1.1. About 77% (91/118) had COVID-19 and 11% (10/91) of them were hospitalized for COVID-19 management. Four cases were severe cases and there was no death. The number of IS was significantly associated with the number of infection (p=0.04), distinct from hospitalization and severity (p=0.82 and 0.50), and there was no significant difference in outcomes between SOTRs received ≥ 3 doses of the COVID-19 vaccine and those received 0-2 doses (p=1.00, 0.21 and 1.00, respectively). Multiple logistic regression showed age at SOT and re-SOT as factors associated with number of COVID-19 (p=0.03, CI 0.36-0.96 and p=0.03, CI 1.74-6431.8). In vaccine immunogenicity analysis, humoral responses in pediatric SOTR were not lower than in adult SOTRs (table 1). However, the vaccine immunogenicity against Omicron was very poor compared to WT or Delta (figure 1).

Conclusion
Pediatric SOTR is susceptible to COVID, especially in older children at SOT and those who have undergone re-SOT. Two or Three doses of vaccination may be suboptimal for Omicron, so additional preventive measures are needed.

Disclosures
All Authors: No reported disclosures
463. Immunogenicity and Safety of mRNA-based SARS-CoV-2 vaccination in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review
Authors: Cardenas-Alvarez Jorge Luis , Triana Abel , Uribe Juan , Morgenstern-Kaplan Dan , Reynolds John M , Raja Mohammed , Natori Yoichiro 
Published: November 2023

Abstract

Background
Immunization is an effective strategy to decrease hospitalization and mortality related to SARS-CoV-2. Since the introduction of mRNA-based SARS-CoV-2 vaccines (BNT1261b2 and mRNA-1273), several studies have outlined the immunogenicity and safety of these in hematopoietic stem cell transplant (HSCT) recipients. Herein, we describe the first systematic review and meta-analysis with pooled data of available evidence on SARS-CoV-2 vaccination in this patient population.

Methods
We conducted a systematic review and meta-analysis of prospective cohort studies up to May 24 2022 in adult HSCT recipients who were vaccinated with ≥1 doses of either mRNA-based SARS-CoV-2 vaccine. The outcomes measured included: a) vaccine immunogenicity, b) safety, and c) breakthrough SARS-CoV-2 infections. Patients with solid organ transplant or prior documented history of SARS-CoV-2 infection were excluded.

Results
1084 unique studies were identified. After abstracts review, 81 full-text studies were assessed by two independent reviewers. Twenty-nine studies were included. A total of 1738 patients were analyzed, out of which 1478 received allogeneic-HCST (Allo-HSCT) and 260 autologous-HSCT (Auto-HSCT). Median IgG positivity after at least 1 dose of vaccination (among studies) was 77.3% (range: 0-100%) among Allo-HSCT and 91.7% (range: 60-100%) among Auto-HSCT. Cellular immunity was reported in 5 studies, describing IFN-gamma and/or lymphocyte response. Median positivity was 42% (range: 24-78%) among Allo-HSCT. Pooled incidence of adverse events reported among all HSCT recipients was 38.72%. The most common side effect was injection-site pain. No grade 5 adverse events were described. De-novo or exacerbation of graft versus host disease was reported in the median of 2.28% (range: 0-6.6%) of Allo-HSCT recipients. Breakthrough COVID-19 infections were reported in both Allo-HSCT and Auto-HSCT in 1/479 (0.2%) and 2/254 (1.29%), respectively.Figure 1.Pooled incidence of antibody positivity after one or more doses of mRNA-based SARS-CoV-2 vaccination in HSCT recipients

Conclusion
mRNA-based SARS-CoV-2 vaccination was immunogenic in HSCT recipients, particularly among Auto-HSCT recipients. One or more doses of mRNA-based vaccine elicited a greater humoral response, compared to that of cellular immunity. Adverse events were common, but often were mild. Breakthrough infections are rare after ≥ 1 doses.

Disclosures
John M. Reynolds, MLIS, Pfizer Inc: Stocks/Bonds
498. Covid-19 Hospitalization Rates in Kidney Transplant Patients Treated with Tixagevimab/Cilgavimab
Authors: Dugan Katherine , Casale Jillian , DeSanto Heather , Dowling Colleen , Smoke Steven 
Published: November 2023

Abstract

Background
Tixagevimab/cilgavimab (T/C) is a monoclonal antibody that was previously authorized for pre-exposure prophylaxis of COVID-19 in individuals with moderate to severe immune compromise. Limited evidence of safety and efficacy in immunocompromised populations was available at the time of authorization. The purpose of this study is to assess the safety and efficacy of T/C for pre-exposure prophylaxis of COVID-19 in a large cohort of kidney transplant patients.

Methods
This was a single-center Institutional Review Board-approved retrospective study. This study included adult patients that received a kidney transplant within the prior two years and received T/C between January 1, 2022, and March 31, 2022. The efficacy population comprised those that received the full 300 mg / 300 mg dose and the safety outcome population included those that received any amount of T/C. Patient demographics, transplant course history, and clinical interventions required during hospitalization due to COVID-19 infection were collected. The primary efficacy outcome was the rate of hospitalization for COVID-19 infection within 6 months of T/C administration. The secondary safety outcome was the rate of serious adverse events. Causality was assessed with the Naranjo algorithm.

Results
A total of 240 patients were reviewed for eligibility and 122 were included. A majority (60%) were male, 34% white and the median age was 57 (IQR 47-62) years old. The efficacy population included 115 patients. Most patients had hypertension (96%), decreased renal function (median CrCl 48 mL/min [33-63]), and had been vaccinated for COVID-19 (98%). The rate of hospitalization for COVID-19 infection within 6 months of T/C was 2% (2). The median time to hospitalization was 158 days. Neither patient required an ICU admission, mechanical ventilation, or experienced mortality. There was no incidence of heart failure, myocardial infarction, or anaphylaxis secondary to T/C. Other adverse effects (2%) considered possibly due to T/C included cardiac arrest (1) and atrial fibrillation (1).

Conclusion
Rates of COVID-19 hospitalization and adverse events within 6 months of T/C were low within a large cohort of kidney transplant patients.

Disclosures
All Authors: No reported disclosures
502. Telemedicine Service for Evaluation of Pediatric Outpatients at High Risk for Severe COVID-19
Authors: Weakley Kathryn E , Bryant Kristina 
Published: November 2023

Abstract

Background
During the COVID-19 pandemic, neutralizing monoclonal antibody (mAb) products received emergency use authorization for treatment of mild to moderate COVID-19 in high-risk patients. Expert consensus guidance recommended individualized risk assessment when considering mAb therapies in children and adolescents, as well as a process to ensure safe and timely administration. In one health system, high demand for mAb to treat adult patients, a finite supply, and a lower risk of severe COVID-19 in children led to allocation of a limited number of doses of mAb for pediatric use. The clinical outcomes of pediatric patients evaluated for allocation of mAb using telemedicine have not been well-described.

Methods
A pediatric infectious diseases (PID) telemedicine service was established to evaluate children with COVID-19 and adjudicate the administration of mAb based on risk assessment, symptoms, physical exam, and the availability of mAb product. Only PID providers were permitted to order mAb in pediatric patients. Demographics and clinical outcomes data were retrospectively collected from the charts of patients evaluated between August 1, 2021 and April 30, 2022.

Results
Two hundred sixty-seven patients were evaluated; 134 medical records have been reviewed to date. The average age was 14.7 years. The most common high-risk condition was obesity. The median time from onset of symptoms to telemedicine evaluation was four days. The median time from COVID-19 diagnosis to telemedicine evaluation was 1.5 days. Six patients were acutely referred to the emergency department (ED); three were admitted, one was given mAb and discharged, and two did not report to the ED as advised. Outpatient mAb was recommended for 12 patients; one declined and 11 received therapy with no serious adverse events. Only two of the remaining 116 untreated patients required COVID-related ED visits within 14 days of telemedicine evaluation; one was admitted with idiopathic thrombocytopenia and the other was discharged. All 134 patients made a full recovery.

Conclusion
Most children evaluated for mAb did not receive treatment and recovered. Telemedicine is a safe and effective way to evaluate patients with COVID-19. Individualized risk assessment can assist with allocation of scarce resources such as mAb.

Disclosures
Kathryn E. Weakley, MD, MSc, Pfizer: Grant/Research Support Kristina Bryant, MD, FPIDS, Enanta: Grant/Research Support|Gilead: Grant/Research Support|Oxford University Press: Royalties|Pfizer: Grant/Research Support
521. A phase II, double blind, placebo-controlled, randomized evaluation of the safety and efficacy of tafenoquine in patients with mild-moderate COVID-19 disease
Authors: Dow Geoffrey 
Published: November 2023

Abstract

Background
Tafenoquine is an 8-aminoquinoline antimalarial approved by the US FDA for malaria prevention and is being evaluated in clinical trials for potential use in other disease areas.

Methods
The safety and efficacy of tafenoquine administered as a 200 mg dose once per day on days 1, 2, 3, and 10 was evaluated over a 28-day period in mild-moderate COVID-19 patients. The primary endpoint was Day 14 clinical recovery from COVID-19 symptoms, defined as cough mild or absent, respiratory rate &lt; 24 bpm, and no shortness of breath or fever. Following a successful futility analysis after n = 86 patients out of a target n = 275 were randomized, the study was terminated and unblinded early to facilitate planning for confirmatory studies.

Results
The proportion of patients not recovered on Day 14 was numerically decreased by 27% in the ITT population [8/45 v 10/42 not recovered in the tafenoquine and placebo arms, P = 0.60] and 47% in the PP population [5/42 v 9/41, P = 0.25]. Amongst individuals who recorded responses in an electronic diary at Day 28, all tafenoquine patients were recovered, whereas up to 12% of placebo patients exhibited lingering dyspnea. Time to clinical recovery from COVID-19 symptoms was accelerated in the tafenoquine arm by about 2-2.5 days. There were two COVID-19 related hospitalizations in the placebo arm and one in the tafenoquine arm. Mild, drug related adverse events occurred in 8.4% of individuals in the tafenoquine arm [v 2.4% in the placebo].

Conclusion
Although this trial was underpowered for the primary endpoint due to its early termination, the data are suggestive of a therapeutic benefit associated with tafenoquine administration in outpatients with mild to moderate COVID-19 disease, and larger studies are planned.

Disclosures
Geoffrey Dow, PhD, 60 Degrees Pharmaceuticals, INC: Board Member|60 Degrees Pharmaceuticals, INC: Inventor on Company covid + malaria patents|60 Degrees Pharmaceuticals, INC: Ownership Interest
614. Experience with Using MALDI-TOF MS to Diagnose Clinically Significant Filamentous Fungal Isolates
Authors: Murray Hugh , Crowe Amy 
Published: November 2023

Abstract

Background
Matrix assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS) technology has revolutionised bacterial diagnostics. Filamentous fungi are a varied and important group of pathogens that cause a wide spectrum of clinical disease. Identification of these traditionally relies upon highly experienced practitioners identifying unique fungal morphological characteristics, along with specific molecular techniques, but MALDI-TOF MS may be a useful alternative. The aim of this retrospective review was to determine how useful MALDI-TOF MS was as an adjunct to filamentous fungi identification at our laboratory service.

Methods
All fungal diagnoses made at St Vincent’s Pathology Melbourne, a large metropolitan laboratory servicing multiple tertiary hospitals and community pathology centres, from 2018 to 2022 were extracted. For clinically significant filamentous fungal isolates, the method of diagnosis was reviewed and categorised into; morphological diagnosis, Bruker MALDI Biotyper® diagnosis, and national reference laboratory diagnosis. All clinically significant isolates where MALDI-TOF MS was attempted were also reviewed.

Results
A total of 256 clinically significant isolates were extracted and reviewed. MALDI-TOF MS was attempted in 59 of these, with success in 39 (66.1%). Of the 20 cases where MALDI-TOF MS was attempted but did not identify the isolate, 16 were diagnosed morphologically and four required send out to the national reference laboratory. 71.2% of MALDI-TOF MS attempts were in the 2021-22 period when successful identification occurred 80.9% of the time. No species/genus appeared more or less readily identifiable. Of the remaining cases, 208 were identified morphologically and nine using the national reference laboratory.

Conclusion
MALDI-TOF MS performed modestly well at identifying filamentous fungi during this study period. Increased use and successful isolate identification in the 2021-22 period likely reflects improvement in the Bruker MALDI-TOF MS database for filamentous fungi. The MALDI-TOF MS system is a useful option in the identification of clinically significant filamentous fungi however morphological and molecular techniques remain important.

Disclosures
All Authors: No reported disclosures
616. Candidemia in a Dominican tertiary care hospital: Six years of history
Authors: Rojas-Fermin Rita A , Guzman-Marte Anel E , Sanchez-Marmolejos Ann Stephany , Cedeño-Bruzual Maria Fernanda , Rojas-Jiménez Javier , Rojas -Jiménez Marlon 
Published: November 2023

Abstract

Background
Despite the high mortality caused by invasive candidiasis or the fact that, as of 2022, a list of priority fungal agents was created by WHO, including Candida species in the three categories, global information is not robust, so it is difficult to estimate the distribution of these infections, species, antifungal resistance patterns, and clinical characteristics of the different types of patients affected globally.

Methods
We performed a retrospective review of patients with candidemia from 2017 to 2022. Data extracted from e-medical records from a teaching hospital with 289 beds included clinical and demographic information, co-morbidities, risk factors, antifungal resistance patterns, and outcomes.

Results
A positive rate of 0.75 percent was seen in 210 cases in 197 patients; 103 of them (52.28%) were men. With 52 cases each, 2021 and 2022 saw the most cases. In six years, the average age was 53 (IQR 54). The most frequent comorbidities were hypertension (52.79%), chronic pulmonary disease (45.68%), and nephropathy (31.98%). Intensive Care Unit stays (74.11%) and prior antibiotic exposure (92.89%) were the most prevalent risk factors, with statistical significance for length of stay in the ICU, the use of vasopressors, and central catheters (p 0.001). Surviving patients had a median length of stay of 26 days (p 0.001). The mortality rate for all patients was 49.2%. C. auris or C. krusei species were not isolated during the study period. The most frequently isolated species were C. tropicalis (40.4%), followed by C. parapsilopsis (23.8%) and C. albicans (20%). Fluconazole resistance was 6% (n=12) across all isolated species, with C. parapsilopsis having the highest prevalence 12% (n=6). C. tropicalis was the species most associated with death, followed by C. albicans.

Conclusion
In the post-pandemic period, we observed an increase in Candida isolates and noted a steady increase in cases of C. glabrata, especially in the ICU. Length of ICU stay, vasopressor use, and central catheters were seen as significant risk factors for candidemia, with older patients being the most affected as well as having higher mortality rates. Although C. auris hasn´t been detected at our institution, we recommend continued surveillance for our infection prevention program.

Disclosures
All Authors: No reported disclosures
625. Association of Eosinophilia with Parasites in Rhode Island Refugees, 2015-2020
Authors: Cruz-Sanchez Margarita , Marin Benjamin Gallo , Osorio Marcela , Teferi Maranatha , Ding Ann , Lorenz Matthew , Michelow Ian C 
Published: November 2023

Abstract

Background
Newly arrived refugees in the United States have high rates of parasitic infections that may contribute to morbidity and mortality. There is little consensus on testing for eosinophils to screen for parasites. We hypothesized that eosinophilia was a useful biomarker for various parasites that could help guide the management of refugees in the future.

Methods
We performed a retrospective chart review of all pediatric and adult refugees attending the only three refugee clinics in Rhode Island from 01/2015 to 12/2020. Individuals whose initial evaluation was delayed or took place in another state were excluded. Data were systematically collated in RedCap, and descriptive statistics were performed.

Results
Of 812 eligible refugees, 147 (18.1%) had eosinophilia ( ⪰ 450/uL). The majority of refugees (505, 62.2%) were from Africa, 242 (29.8%) from Asia, 32 (3.9%) each from the Americas, Europe, and 1 (0.1%) from Australia. Eosinophilia was mild (450-1499/uL) in 113 (76.9%), moderate (1500-4999/uL) in 30 (20.4%), and severe ( ⪰ 5000/uL) in 4 refugees (2.7%)(Table 1). The prevalence of symptoms ranged from none (bloody stools) to 17.1% (abdominal pain). 48 (32.7%) refugees with eosinophilia tested positive for a parasite in their stool by O&P and/or PCR assay. The most prevalent organisms were Giardia (n=25) and Blastocystis hominis (n=22). An additional 22 (15%) tested positive for Schistosoma or Strongyloides (Table 2). Forty-six (31.3%) refugees with eosinophilia were treated with antiparasitic agents. Sixty-three (42.9%) had no follow-up eosinophil tests. Of the 84 patients who did have monitoring of their eosinophilia during the first year after arriving in the US, eosinophilia resolved in only 53 (64.6%). One patient (0.7%) had a severe complication: Strongyloides hyperinfection syndrome. Five patients (3.4%) received alternative diagnoses that explained their eosinophilia, including eczema, myelofibrosis, and a drug allergy.

Conclusion
Eosinophilia occurred in almost 1/5 of newly arrived refugees in RI. Diagnostic, therapeutic, and follow-up practices varied substantially. Approximately 1/3 of evaluable refugees had persistent eosinophilia at one year. A standardized screening approach for eosinophilia is needed to inform appropriate management.

Disclosures
All Authors: No reported disclosures
636. Epidemiology and Outcome Among the Elderly Hospitalized Patients with Respiratory Syncytial Virus Infections
Authors: Bhargava Ashish , Szpunar Susan M , Malik Ambreen , Tehaili Hussein , Sharma Mamta 
Published: November 2023

Abstract

Background
Elderly patients with congestive heart failure (CHF), chronic lung diseases (CLD) and immunocompromised conditions are considered a high-risk category for severe respiratory syncytial virus (RSV) infections. Our study aimed to identify RSV disease epidemiology and its outcomes among the elderly hospitalized patients with and without high-risk conditions (HRC).

Methods
We conducted a multicenter historical cohort study of adult patients for laboratory-confirmed RSV-related diseases in Ascension hospitals in southeast Michigan between January 2017 and December 2021. Patients were identified using ICD 10 codes for RSV diseases. Patients with HRC were those elderly patients with CHF, CLD and immune-compromised conditions. Data were analyzed using SPSS v. 29.0.

Results
Among 240 patients, 31.3% (75) were without HRC whereas 68.7% (165) had at least one HRC. The mean (sd) age of the patients without HRC was 81.9 + 8.9 years, 47 (62.7%) were female, 52 (69.3%) were white and mean body mass index (BMI) was 28.9 + 8.3 years. The mean (sd) age of the patients with HRC was 76.6 + 7.7 years, 111 (67.3%) were female, 125 (75.8%) were white and BMI was 29.8 + 9.0 years. Major comorbidities among patients without HRC compared to those with HRC were hypertension (77.3% vs 69.1%), cerebrovascular condition (25.3 vs 10.9%), diabetes (18% vs 37.6%), dementia (21.3% vs 8.5%), and chronic kidney disease (CKD) (16% vs 21.2%). Current smokers were 30.7% vs 66.1% among patients without HRC compared to those with HRC. On admission, median (IQR) qSOFA scores were 0 (0-2) vs 1 (0-3) among patients without HRC compared to those with HRC. Lower respiratory tract infections (LRTI) were 32% vs 43%, acute kidney injury (22.7% vs 24.2%), liver injury (1.3% vs 3%), mechanical ventilation (6.7% vs 9.1%), pressors (1.3% vs 1.8%), and ICU requirement (10.7% vs 15.2%) among patients without HRC compared to those with HRC. In-hospital mortality were 1.3% vs 5.5% among patients without HRC compared to those with HRC.

Conclusion
In our study, elderly patients with HRC were younger, smokers with higher incidence of diabetics, CKD, higher qSOFA on presentation with higher LRTIs, and other complications including mortality. Targeted risk mitigation strategies can help reduce disease burden and cost associated with RSV infections.

Disclosures
All Authors: No reported disclosures