bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1967. Characteristics of the first immunocompromised patients to receive Sipavibart as an early access treatment for COVID-19 pre-exposure prophylaxis in France
Authors: Loubet Paul , Gaborit Benjamin , Salpin Mathilde , Gardeney Hélène , Benotmane Iliès , Systchenko Thomas 
Published: January 2025

Abstract

Background
Immunocompromised patients account for a large proportion of COVID-19 hospitalizations and deaths, even in the most recent periods, despite having received several COVID-19 vaccine doses. Monoclonal antibodies effectively prevented COVID-19 in the general population in randomized control trials and the immunocompromised population in real-world studies. Unfortunately, the emergence of new variants precluded their use. Sipavibart (AZD3152) is an investigational long-acting monoclonal antibody designed to provide broad coverage across Omicron and ancestral viral variants currently being studied in the SUPERNOVA prevention trial. France was the first country to grant Sipavibart as a COVID-19 pre-exposure prophylaxis treatment in immunocompromised individuals with an early access authorization in December 2023.

Methods
We performed a retrospective multicentric study in France, including the first consecutive patients to receive one intramuscular dose of Sipavibart in January and February 2024, to collect their characteristics and COVID-19-related medical history.

Results
Overall, we included 47 patients with a median age of 61 years (IQR:64—69) and 64% male. The three main immunosuppressive conditions were Stem cell transplants (38%), solid organ transplants (32%), and immune-based therapies (mostly Rituximab) (19%) for chronic inflammatory diseases or haematologic malignancies. Nearly half had hypogammaglobulinemia and 71% had at least another key comorbidity (Table 1). 15% and 11% had a history of severe and persistent COVID-19, respectively. The median number of COVID-19 doses was 4 (IQR 3-6), and nearly one-third had previously received previous generation of monoclonal antibodies for COVID-19 prophylaxis (Casirivimab/imdevimab or Tixagevimab/Cilgavimab). SARS-CoV-2 serology results before Sipavibart administration were available in 11 patients (without Immunoglobulins substitution). The median anti-Spike IgG titers was 30 UI/L (IQR 0-179).

Conclusion
The first patients to receive Sipavibart in France had different profiles, but they were all highly immunocompromised with frequently associated hypogammaglobulinemia and other chronic conditions.

Disclosures
Paul LOUBET, MD, PhD, Astrazeneca: Advisor/Consultant|Gilead: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant Iliès Benotmane, n/a, Astrazeneca: Advisor/Consultant|Astrazeneca: Board Member
P-1974. Surface Protein Profiling of Extracellular Vesicles: A Novel Biomarker Approach for Long COVID Diagnosis?
Authors: Ikeda Gentaro , Jagannathan Prasanna , Leki Mario , Inoue Hiroyuki , El Kamari Vanessa , Dadhania Arya V , Miglis Mitchell , Shafer Robert W , Geng Linda N , Yang Phillip C , Bonilla Hector F 
Published: January 2025

Abstract

Background
Extracellular vehicles (EVs) are lipid bilayer vesicles secreted by all cell types into the circulation. EVs carry an array of biomolecules indicative of their origin cells and act as cargo vesicles capable of delivering proteins, mitochondria, and viral particles. However, whether long COVID affects the profile of plasma EVs remains unknown.

Methods
Plasma samples were selected from the Stanford repositories of Long COVID participants—seventy-six plasma samples from patients with documented SARS-CoV-2 infection. Twenty-five participants had full recovery (10 months post-infection, Stanford Lambda Trial), 24 patients with Long COVID with CFS phenotype and 27 with ME/CFS from the Stanford Long COVID clinic. Plasma EVs were isolated using size-exclusion columns (qEV, Izon Science). The positivity for surface markers and mitochondrial membrane potentials of the plasma EVs were evaluated by flow cytometry. Samples were stained with pre-titrated volumes of the following fluorochrome-conjugated monoclonal antibodies: CD45 leukocytes, CD3/T cells, CD20/B cells, CD14/Monocytes, CD16/NK cells, CD144/endothelial cells, CD41a/Platelets, CD56/neural cell adhesion molecule (NCAM), and Mitotracker deep red/mitochondrial membrane potential.

Results
The total EV counts and the proportion of mitochondria-positive were decreased in Long COVID group compared to the COVID recovery group (5.02 x 106 vs. 1.92 x 107 /mL, and 42.7 vs. 56.7%, respectively). Compared with the recovery group, Monocyte and NK cell-derived EVs were significantly increased, whereas Endothelial cell-derived EVs were decreased in the Long COVID group. The EVs from the Long COVID group consistently exhibited lower positivity of mitochondrial membrane potential regardless of the parental cells. No difference was observed in plasma EVs derived from NCAM positive cells. NK cell proportion is the only difference between LC/CSF and CSF (P= 0.046).

Conclusion
Patients with Long COVID showed alterations in plasma EV profiles. These findings may offer insights into the pathogenesis of long COVID.

Disclosures
All Authors: No reported disclosures
P-1978. Long-Term Mast Cell Activation Patterns in Systemic and Tissue-Resident Compartments Following COVID-19: Insights from a 2-Year Post-Infection Study
Authors: Augustin Max , Picard Lea Katharina , Zenev Elisabeth , Ball Melanie , Rostocki Isabella , Pracht Elisabeth , Rauschning Dominic , de Silva Ute Sandaradura , Lin Ting-Huee , Petschnak Sophia , Kirschner Harald , Stingl Michael , Komenda-Lett Martin , Födinger Manuela , Wenisch Christoph , Lehmann Clara , Zoufaly Alexander 
Published: January 2025

Abstract

Background
The pathogenesis of Post-COVID syndrome (PCS) following mild coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) remains unclear. In particular, the involvement of activated mast cells (MC) in the highly angiotensin converting enzyme 2 (ACE2) expressing small bowel, the largest lymphoid organ, might be significant in PCS pathogenesis. This study aimed to elucidate the role of activated MC, residual SARS-CoV-2 spike (S) protein and zonulin (a marker for impaired intestinal integrity), in the context of PCS, examining peripheral blood (PB) and terminal ileum (TI) 2 years post-infection.

Methods
In this cross-sectional, controlled study, paired PB and TI samples were obtained from 21 SARS-CoV-2 convalescents with (PCS+) and 11 without PCS (PCS−). CD117+CD25+ activated MC and residual S protein were assessed using fluorescent immunohistochemistry on sections of the the ileal tissue from the gut. Tryptase, zonulin and S protein were quantified in serum by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assessed frequencies of T-cells (CD3+CD4+ (TCD4), CD3+CD8+ T-cells (TCD8)) and CCR7±CD27± memory subsets (TCM: T central memory, TEM: T effector memory) on mononuclear cells of PB and TI.

Results
Among PCS+ and PCS−, median follow up was 22 and 18 months post-infection, 81% and 73% were female, and 57% and 55% had pre-existing conditions of which arterial hypertension, chronic lung disease and diabetes mellitus were the most frequent. Compared to PCS−, PCS+ expressed significantly more MC (p&lt; 0.0001) in ileal sections, along with elevated levels of tryptase (p=0.0196) and zonulin (p=0.024) in PB. S protein, by contrast, was undetectable in PB of PCS+ and PCS− even 2 years post-infection. In TI however, the frequency of tissue-resident S protein-infected cells was significantly higher in PCS+ compared to PCS− (p=0.0135). Interestingly, systemic tryptase levels correlated positively to elevated TCM in TI (r=0.7407, p=0.0034).

Conclusion
Elevated MC activity and S protein in the TI, along with increased tryptase and zonulin levels in PB, indicate ongoing immune activation and intestinal damage in the TI of PCS+. Understanding the role of tissue-resident MC in PCS pathogenesis could lead to targeted therapies.

Disclosures
All Authors: No reported disclosures
P-1987. Effectiveness of Tixagevimab-Cilgavimab as Pre-Exposure Prophylaxis in Patients Undergoing Hematopoietic Cell Transplant or Chimeric Antigen Receptor T-cell Therapy
Authors: Juneja Arjun , Armistead Paul , Thakkar Astha , Ptachcinski Jonathan , Herman Catherine A 
Published: January 2025

Abstract

Background
Tixagevimab-cilgavimab (tixa-cil), was approved for emergency use authorization by the FDA in December of 2021 for pre-exposure prophylaxis of the COVID-19 virus in immunocompromised populations due to concerns about vaccine efficacy. Data regarding real world efficacy of tixa-cil in preventing SARS-CoV-2 infection in immunocompromised patients is limited.Table 1Patient Demographics

Methods
We conducted a retrospective analysis of all patients who had received hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell (CAR-T cell) therapy between 12/1/2021-12/1/2022 at the University of North Carolina Bone Marrow Transplant and Cellular Therapy Program and were eligible to receive tixa-cil as pre-exposure prophylaxis. Patient demographics, underlying malignancy type, COVID-19 vaccine status, data and number of tixa-cil injections, cellular infusion type, presence of GVHD, adverse events, and cause of death if related to COVID-19 were all collected.Table 2Therapeutic Agents Used For Treatment of COVID-19

Results
Of 184 eligible patients, 113 (61%) received at least one tixa-cil injection. Forty-five cases of either documented or reported COVID-19 infection following cell infusion (including 8 recurrent infections) were identified. Of the 113 patients who received tixa-cil, 14 (12%) had a documented positive COVID test within 6 months. In comparison, 23 (32%) of the 71 patients who did not receive tixa-cel had a documented positive COVID test, (p=0.0013, Fisher’s exact test), OR=0.2951. Of 13 COVID-related hospitalizations, only one occurred in a patient who received tixa-cil, (p=0.0048, Fisher’s exact), OR=0.0641.
Number of Patients with Documented COVID Infections Who Did and Did Not Receive Tixa-Cil

Conclusion
Our findings indicate that tixa-cil was effective as pre-exposure prophylaxis in reducing SARS-CoV-2 infection and disease severity in a highly immunocompromised patient population. While the FDA removed authorization for ongoing use of tixa-cil in January 2023 due to its ineffectiveness against the Omicron variants, our data suggest that mAbs are highly effective in providing protective passive immunity to patients at risk of impaired vaccination responses. Pemibivart, a new anti-SARS-CoV-2 spike protein mAb, was recently authorized by the FDA. Our results suggest a clinical benefit for this therapy; however, real world studies will be needed to determine actual efficacy.
Number of Patients Hospitalized Related to COVID Infection Who Did and Did Not Receive Tixa-Cil

Disclosures
Jonathan Ptachcinski, PharmD, Johnson & Johnson: Company Employee
P-2012. Predicting Persistent SARS-CoV-2 Shedding in Immunocompromised Patients: A Probability-Based Approach
Authors: Chang Eui Jin , Kim Jun-Won , Jang Choi-Young , Kang Sung Woon , Kim Ji Yeon , Bae Seongman , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Yang Jeong-Sun , Kim Kyung-Chang , Lee Joo-Yeon , Yun Sung-Cheol , Kim Sung-Han 
Published: January 2025

Abstract

Background
Prolonged SARS-CoV-2 shedding frequently occurs in immunocompromised patients, making the determination of their isolation periods challenging. This study aims to estimate the probability of viral clearance in immunocompromised patients, stratified by elapsed days and other relevant variables.
Figure 1
The estimated probability of viral clearance along days, stratified by SARS-CoV-2 PCR Ct value and immunocompromised conditions

Methods
This prospective study was conducted at Asan Medical Center, a 2,732-bed tertiary teaching hospital in the Republic of Korea, from January 2022 to May 2023 during the prevalence of the Omicron variant. We enrolled immunocompromised patients, defined as 'moderately or severely immunocompromised' according to CDC guidelines. All participants, diagnosed with COVID-19 via nasopharyngeal swab PCR, provided weekly respiratory specimens for viral load measurement using real-time RT-PCR. Positive samples underwent viral culture. The Cox time-varying proportional hazard model was applied to identify significant predictors of viral culture negative conversion, employing backward elimination for model refinement. Analyses were conducted using R software, version 4.3.2, and included the assessment of viral copy number dynamics and treatment effects on viral shedding probabilities.
Baseline characteristics of the immunocompromised patients

Results
In a cohort of 70 immunocompromised patients, 48 (68.6%) had hematologic malignancies and 22 (31.4%) underwent solid organ transplants. Univariate and multivariate analyses revealed that the use of B-cell depleting agents, CAR T-cell therapy, and viral copy number significantly influenced viral culture negative conversion. These findings were incorporated into a refined model to predict viral shedding probabilities. Patients with a history of both B-cell depleting agents and CAR T-cell therapy exhibited the lowest negative conversion rates, with median durations of viral shedding from 76 days to undeterminable depending on SARS-CoV-2 Ct values. In contrast, patients receiving neither treatment showed markedly faster viral clearance, typically within one to two months after COVID-19 diagnosis, regardless of Ct values.
Predictive factors for viral culture negative conversion in the immunocompromised patients

Conclusion
Ending the isolation of immunocompromised patients with COVID-19 should be determined individually, based on the viral copy number at specific time points and treatment conditions.
Table 3
Probability of culture-negative conversion among immunocompromised patients based on treatments received, days elapsed after diagnosis, and SARS-CoV-2 PCR results

Disclosures
All Authors: No reported disclosures
P-13. Awareness, Attitudes, Knowledge and Barriers Related to Adult Pneumococcal Vaccination among Internal Medicine Residents and Fellows in University Hospital, Thailand
Authors: Roongjiraroj Thanasate , Phuensan Pawat 
Published: January 2025

Abstract

Background
Pneumonia is the leading cause of global mortality with Streptococcus pneumoniae as a leading pathogen in high-risk adults. Although vaccination is crucial for preventing pneumococcal infections, its uptake remains suboptimal in Thailand. Internists, pivotal in managing such patients, are at the forefront of promoting vaccination. Therefore, this study aimed to explore factors related to physicians’ pneumococcal vaccine administration among high-risk adults in university hospital in Thailand.

Methods
This web-based survey cross-sectional study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand (university hospital). Participants were residents and fellows in Department of Medicine. The questionnaire included demographic data and vaccine-related inquiries in various aspects including awareness, attitudes, and knowledge towards pneumococcal vaccination.

Results
The study involved 93 participants. Demographic data was presented in table 1. Awareness of pneumococcal vaccination was generally high and attitudes were positive. Overall, participants showed a good knowledge of pneumococcal infection, but participants with lower rate of vaccination administration had significant lower knowledge than participants with higher rate of vaccination administration (table 2). Key barriers to vaccination included limited access to advice and recording systems, cost issues, and a lack of specialized consultation. Potential quality improvement strategies were electronic vaccination record, easy-to-access guideline, and vaccine consultation clinic.

Conclusion
This study emphasizes the importance of addressing barriers like limited access to vaccination advice and recording systems, cost issues, and a lack of specialized consultation. Implementing targeted interventions and raising knowledge and awareness of vaccination are key steps toward reducing the burden of pneumococcal infections. These results would lead to improvement of residency and fellowship training program and vaccination practice in our hospital.

Disclosures
Pawat Phuensan, MD, MSc, GSK: Grant/Research Support|GSK: Honoraria|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Siam Pharmaceutical: Grant/Research Support|Takeda: Honoraria
P-2129. Analytical Validation of a Next-Generation Sequencing Assay for the Detection of Microbial Pathogens in Human Plasma
Authors: Bacon Curtis , Bixler Ellis , Cowden Scott , Nutt Jamie , Kleiboeker Steve 
Published: January 2025

Abstract

Background
Fungal and acid-fast bacteria (AFB) infections can be a serious complication for immunosuppressed patients. Identification of the pathogen involved in invasive fungal/AFB infections (IFIs) can allow for reduced time to initiation of the appropriate targeted therapy through elimination of ineffective therapies. Current fungal/AFB diagnostics suffer from low sensitivity/specificity, invasiveness (e.g., biopsy or antigen), have long turnaround times (e.g., culture), and/or require an a priori hypothesis regarding the causative pathogen (e.g., PCR based methods). To overcome shortcomings in fungal/AFB diagnostics, an unbiased next-generation sequencing (NGS) approach can be utilized to characterize pathogen cfDNA present in a patient blood sample.

Methods
Sequencing of IFIs through hybrid capture has the potential to detect a broad range of pathogens yet can still specifically target the most clinically relevant. Compared to standard whole-genome sequencing methods, hybrid capture followed by NGS can be more specific and sensitive due to an enrichment step using probes specific to cfDNA targets of interest. This additional enrichment step can result in more sequencing reads being dedicated to cfDNA derived from pathogens of interest rather than to cfDNA derived from non-relevant organisms. Here is described a hybrid capture assay that uses &gt;30,000 probes to detect &gt;600 Fungal and select AFB species in plasma.

Results
Cutoffs for target coverage and kmers/million were established through ROC analysis of 170 contrived plasma samples resulting in an analytical specificity of ∼96% and a sensitivity of ∼1,200 molecules/mL. 98% of the 40 contrived samples used for accuracy were correctly identified while 100% intra- and 93%-inter assay precision was achieved. In silico validation demonstrated the assay’s ability to detect closely related species unable to be tested at the bench. Several species have been detected in the initial clinical samples received thus far, however, all have been below the reportable cutoff values.

Conclusion
The analytical validation described here demonstrates the analytical performance of hybrid capture in human plasma.

Disclosures
Curtis Bacon, PhD, Eurofins Viracor: employee Ellis Bixler, n/a, Eurofins Viracor: Employee Scott Cowden, n/a, Eurofins Viracor: Employee Jamie Nutt, n/a, Eurofins Viracor: Employee Steve Kleiboeker, PhD, Eurofins: employee|Eurofins: Stocks/Bonds (Public Company)
P-2140. Clinical Review of Respiratory Tract Infections Caused by Exophiala dermatitidis Misidentified as genus Rhodotorula: Case Series
Authors: Setoguchi Daichi , Iwanaga Naoki , Hirayama Tatsuro , Yoshida Masataka , Takeda Kazuaki , Ide Shotaro , Tashiro Masato , Takazono Takahiro , Kosai Kosuke , Izumikawa Koichi , Yanagihara Katsunori , Mukae Hiroshi 
Published: January 2025

Abstract

Background
Exophiala dermatitidis is a black fungus isolated from wet environments such as soil and baths. Human infections have been reported chiefly as skin and soft tissue infections, and respiratory infections have been extremely rare. The fungus is dimorphic and known to be yeast-like in culture, changing to filamentous fungi over time. The fungus is often misidentified as yeast during the first few days of culture, and preliminary experiments have shown that it can be misidentified as Rhodotorula spp. by commercially available yeast identification kits.

Methods
Genetic identification was performed using 44 strains isolated from airway specimens over the past 11 years from July 2012 to September 2023, except for one difficult to culture, by determining the sequence of the ITS and D1/D2 regions. Cases genetically identified with E. dermatitidis were examined retrospectively for clinical information except for seven cases identified of the same cases.

Results
Of the 43 strains identified genetically, 22 were identified as E. dermatitidis, indicating that they were misidentified in approximately 50% of the cases; analysis of the clinical information of the 15 cases identified as E. dermatitidis and for which a retrospective search was possible showed that chronic lower respiratory tract infection or pneumonia due to E. dermatitidis was definite in six cases, active infection was possible in five cases and airway colonization only in four cases. Comorbidities included pulmonary non-tuberculosis mycobacterium (NTM) in five cases, chronic progressive pulmonary aspergillosis (CPPA) in three cases, and pulmonary nocardiosis in one case, suggesting concurrent chronic pulmonary infections due to other microbes. Steroid and immunosuppressive agent use was observed in ten cases. Five of the six definite cases responded to azoles, and one case resolved spontaneously with only a reduction of the immunosuppressive drugs. Drug sensitivity testing showed that all cases were resistant to Candin and sensitive to azoles and polyenes.

Conclusion
E. dermatitidis is a dimorphic fungus that is time-consuming to culture and may have been underestimated previously, misidentified as Rhodotorula spp. In addition to NTM and CPPA, E. dermatitidis might be differentiated in chronic lung infections.

Disclosures
Hiroshi Mukae, M.D., Ph.D., AstraZeneca: Lecture fees|Gilead Sciences: Lecture fees|GSK: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Lecture fees|Shionogi & Co., Ltd.: Advisor/Consultant|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Lecture fees