bluuebunny/crossref_metadata_2025 huggingface dataset:
P-2268. Candida tropicalis Invasive Infection in Febrile Neutropenia, a High Mortality Infection
Authors: Arango Marcos , Ramirez Isabel C
Published: January 2025

Background

Invasive candidiasis due to species other than Candida albicans emerges as a problem in neutropenic patients receiving antifungal prophylaxis, due to decreased susceptibility to triazoles. Candida tropicalis is the most frequently species in this population and is associated with higher mortality when compared to Candida albicans. The aim of this study is to characterize the neutropenic population with invasive candidiasis and establish differences in outcome of patients with Candida tropicalis infection compared to other Candida species.

Characteristics of patients with invasive candidiasis

Methods

Retrospective cohort study of patients with hematological malignancies undergoing chemotherapy who developed invasive candidiasis between 2010 and 2022. Comparison of two qualitative variables was performed using Pearson's Chi-square test or Fisher's exact test. Estimation of group survival was performed using the Kaplan-Meier method and comparison of survival functions with the Log-Rank test.

Results of multivariate analysis of risk factors associated with adverse outcomes.

Results

At the time of fungemia, 85% of patients had active malignancy, with a median of 14 days of neutropenia until the development of infection. 15% of patients had mucositis and up to 60% had concomitant diarrhea. 95% had previously received antibiotics and 87.5% had a central catheter. In 40% of the patients, the infection occurred as a breakthrough infection and in 37.5% it was associated with azole resistance. 32.5% of cases were associated with deep-seated infection and 25% had persistent fungemia. The 30-day mortality of patients with candidemia due to C. tropicalis was higher than that experienced by subjects with candidemia due to other species (69% vs. 35%, p = 0.034). The median overall survival was 15 days (95% CI 12-18) for the first group. Multivariate analysis showed that C. tropicalis infection was associated with an increased risk of all-cause mortality. The risk factors associated with cutaneous lesions were C. tropicalis infection and azul resistance.

Overall survival of study patients

Conclusion

Patients who develop C. tropicalis candidemia during febrile neutropenia after chemotherapy for hematologic malignancies have a higher mortality than those infected with other Candida species. Azole resistance emerges as a threat given routine prophylaxis in this population, so mitigation strategies are necessary.

Disclosures

All Authors: No reported disclosures
P-2269. Mixed Fungal Infection in Patients with Hematological Malignancies
Authors: Ramirez Isabel C
Published: January 2025

Background

Invasive fungal infection (IFI) is a complication of neutropenia related to hematological malignancy that carries high mortality. Invasive candidiasis remains the predominant cause of yeast infection, followed by molds, primarily Aspergillus, Fusarium, and Mucorales. The clinical spectrum varies, with fungemia and pulmonary IFI being the most common; however, sinusitis, sinopulmonary and disseminated diseases also occur or may have overlapping manifestations. Commensalism and opportunism between microorganisms can favor superinfection as has been previously demonstrated with bacteria and yeasts, virus and mold species, however, mixed fungal infections (MFI) of both yeast and molds are rarely found simultaneously.

Characteristics of patients with mixed fungal infection

Methods

Medical records and laboratory data of patients with hematological malignancies with IFI were retrospectively reviewed over a 10-year period at a tertiary care hospital. Fungal infection was diagnosed according to the EORTC/MSG criteria, and MFI were defined as the simultaneous isolation of different fungal species in the same or in different representative microbiological specimens.

Results

22 episodes of MFI were found. In 90% of cases it was associated with prolonged neutropenia, most patients had acute leukemias. The most common manifestations were pulmonary IFI and fungemia (10/22), followed by sino-pulmonary IFI and fungemia. Infection by yeast and molds occurred in 13/22 cases and by different species of molds in 9/22 cases. The most common MFI was aspergillosis associated with invasive candidiasis (7/22), followed by aspergillosis and fusariosis (3/22) and aspergillosis associated with Curvularia infection (3/22). Breakthrough infection occurred in 11 of 22 cases. Mortality was 50%, those who survived, all resolved neutropenia.

Conclusion

MFI are rare and often associated with high mortality, neutropenia resolution is an important factor for survival. Mold infection is usually manifested with sino-pulmonary involvement, so it is considered that it is caused by the same fungus. However, this study demonstrates that the etiology of sinusitis may be different from that of pulmonary involvement and, therefore, highlights the need to emphasize invasive diagnosis at each of the sites involved.

Disclosures

All Authors: No reported disclosures
P-2270. Spectrum of Invasive Mold Sinusitis in Adults with Hematological Malignancies
Authors: Ramirez Isabel C
Published: January 2025

Background

Invasive mold sinusitis (IMS) occurs exclusively in immunocompromised patients. In patients with hematologic malignancies, it is associated with mortality and may affect cancer-related survival by causing delay of the chemotherapy regimen.

Clinical characteristics of patients with IMS

Methods

The records of adult patients with hematologic malignancies and proven or probable IMS over a 10-year period at a tertiary care hospital in Medellin, Colombia were retrospectively reviewed. Clinical aspects and results were evaluated

Microbiological data of IMS

Results

We identified 24 episodes of IMS in 23 patients. In all cases manifested with nasal congestion, 27% of the episodes occurred in acute leukemias, 50% in refractory disease and 22.2% in medullary aplasia and hematopoietic stem cell transplantation; 16.6% manifested as a breakthrough infection. 21 episodes were related to neutropenia at the time of diagnosis. Aspergillus spp. was isolated in 12 (52.1%) episodes, Fusarium spp. in 6 (26%). Other etiologies were Curvularia spp., Hormographiella aspergillata, Tropicoporus tropicalis, Rhizomucor spp., Cladosporium and Lasiodiplodia spp. In 5 episodes there was fungal coinfection mainly with Aspergillus spp. In 26% of the cases the sinusitis was related to invasive pulmonary aspergillosis (IPA). The galactomannan antigen test was positive in patients with IPA and negative in cases of isolated sinusitis. All patients underwent surgical debridement and had positive histology and microbiological isolation with morphological and/or molecular identification. 13 episodes were treated with voriconazole and the response was defined as complete and partial in 10 and 8 of the episodes respectively. 7 patients died, 5 due to refractory hematological disease and one attributable to infection as it was rhinosinusal mucormycosis.

Conclusion

IMS is an expected complication of cytotoxic chemotherapy and is usually associated with profound and prolonged neutropenia. It is related to high mortality given the underlying malignant disease. Although Aspergillus spp. is the most common etiology, there are other molds that must be taken into account for better therapeutic guidance and therefore the need for invasive diagnosis is highlighted.

Disclosures

All Authors: No reported disclosures
P-2279. Breakthrough Invasive Fungal Infections in Patients with Acute Myeloid Leukemia on Anti-Fungal Prophylaxis (2022)
Authors: Nelson Julia M , Azim Ahmed Abdul , Bhowmick Tanaya , Majumdar Anjali , Bhatt Pinki , Schmidt Elizabeth , Hayman Jaclyn , Narayanan Navaneeth , Mohayya Sana M , Baireddy Moulika , Vemulapalli Bhargav
Published: January 2025

Background

Patients with hematologic malignancies, particularly Acute Myeloid Leukemia (AML), are at high risk for invasive fungal infection (IFI). Mold Active-Primary Antifungal Prophylaxis (MA-PAP) is recommended in these patients to prevent IFI, which carries high morbidity and mortality risk. Very few studies have compared rates of breakthrough IFIs (bIFIs) in AML patients treated with different MA-PAP regimens.

Methods

This is a single-center, retrospective cohort study of adults with AML aimed at determining the efficacy of MA-PAP and the incidence and characteristics of bIFIs. We reviewed the medical records of patients ≥ 18 years old with a diagnosis of AML admitted to Robert Wood Johnson University Hospital (RWJUH) in 2022 and received MA-PAP with either Micafungin (MYC), Voriconazole (VCZ), Posaconazole (PCZ), or Isavuconazole (ISA) for > 7 days. bIFIs were classified as possible, probable or proven (based on the modified EORTC/MSG criteria) if they occurred after at least 7 days of MA-PAP initiation to within two weeks of discontinuation.

Results

A total of 87 patients were included. Twenty patients (24.1%) experienced a total of 22 bIFI events, with 2 considered proven, 5 probable, and 15 possible. The incidence of bIFI was 15.4% for MYC, 18% for VCZ, 28% for ISA, and 0% for PCZ. 59.1% of bIFIs were in patients that were neutropenic for > 2 weeks at the time of bIFI. Proven bIFI were due to Candida Krusei and Mucormycosis. The mean length of hospital and ICU stay was the longest in the MYC group at 31 and 6 days respectively. Those who received VCZ experienced the highest number of reported adverse events (28, 41%) most often hepatotoxicity. Mortality was highest in PCZ (15.4%) followed by VCZ (11.5%).

Conclusion

Our institution experienced a high rate of bIFI, particularly among patients who received MA-PAP with VCZ or ISA. Prolonged neutropenia was an important risk factor for bIFI. Larger cohort studies are needed to accurately assess the risk factors and possibly mitigate the incidence of bIFI in this patient population on various MA-PAP. A comprehensive 10-year retrospective study is currently underway at RWJUH.

Disclosures

Pinki Bhatt, MD, Sanofi: Grant/Research Support Navaneeth Narayanan, PharmD, MPH, BCIDP, Astellas: Honoraria|Beckman Coulter: Honoraria|Merck: Grant/Research Support|Shionogi: Grant/Research Support
P-2280. Community-Acquired Pneumonia in Immunosuppressed Patients Admitted to the ICU
Authors: Viñán Garcés André Emilio , Sanabria-Herrera Natalia , Duque Sara , Garcia-Gallo Esteban , Guerrón-Gómez Gabriela , Reyes Luis Felipe F
Published: January 2025

Background

Severe community-acquired pneumonia (sCAP) remains a crucial infectious cause of global mortality, accounting for a significant proportion of ICU admissions. Immunosuppressed patients frequently develop sCAP; however, the clinical characteristics and clinical outcomes of patients admitted to the ICU due to sCAP are not clear. Here, we attempted to bridge this gap in the literature.

Figure 1

Isolated microorganisms in respiratory samples. A. General cohort; B. No immunosuppression risk factors group; C. Immunosuppression risk factors group

Methods

This secondary analysis of the prospective MIMIC-IV database included adults admitted to the ICU with CAP diagnosis. Patients were stratified based on the presence or absence of immunosuppression. Bivariate, multivariate, and survival analyses were conducted to identify factors associated with mortality within the immunosuppressed and their impact on hospital mortality.

Figure 2

Kaplan-Meier survival curve of 1-year after discharge survival probability stratified by immunosuppression status. Patients with and without immunosuppression are represented, the first group with 1 (blue) and the last with 0 (red).

Results

A total of 4742 patients were included, with 1502/4742 (32%) being immunocompromised. The mean age (SD) was 66 ±16.1years, with 2627/4742 (55.4%) males. A total of 1384 respiratory isolations were obtained with Staphylococcus aureus (43.2% vs. 40.6%; p= 0.45) and Pseudomonas aeruginosa (10.20 % vs 11.69 %; p= 0.39) as the most representative in both groups (Figure 1). Immunosuppressed patients presented both higher Charlson comorbidity index (7.12, SD 3.14 vs. 4.97, SD 2.59; p < 0.01) and infection severity by the SAPS II score (39, [31-49] vs 37, [ 29-46]; p < 0.01). Immunosuppression was associated with increased mortality rates (IH: OR 1.99 [95% CI: 1.63-2.43]; 6 M: OR 1.79 [95% CI 1.52-2.12]; 12 M: OR 1.93 [95% CI 1.64-2.28]; p < 0.01) and both solid malignancy and infection severity were positively correlated with mortality (Table 1). Immunosuppressed patients had a lower survival rate even after adjusting for disease severity (Figure 2).

Table 1

Univariate and multivariate analysis of risk factors associated with in-hospital, 6-month, and 12-month deaths in the immunosuppressed population.

Conclusion

Immunosuppression was independently associated with mortality and lower survival in sCAP patients. An individualized patient risk approach is necessary as immunosuppression affects mortality differently than immunocompetent patients.

Disclosures

All Authors: No reported disclosures
P-2284. "Low Incidence of Bacterial and Viral Infection after Robotic Surgery Kidney Transplant"
Authors: Shah Nikita , DiStefano Nicholas , Morsi Mahmoud , Viotti Julia Bini , Simkins Jacques , Anjan Shweta , Guerra Giselle , Vianna Rodrigo , Natori Yoichiro
Published: January 2025

Background

Kidney and kidney-pancreas transplantation should benefit patients with end-stage kidney disease and diabetes mellitus. Immunosuppressive medication are required to prevent rejection and maintain graft. However, immunosuppression increases the risk of infection. Surgical procedures also lead to inflammation post-kidney transplant, which results in opportunistic viral/fungal infections. Robotic surgery is well established to be less invasive and cause less harm in the short term for patients. However, it has never been investigated for infectious disease complications post-kidney transplantation.

Methods

This was a single-center, retrospective cohort study conducted at a large kidney transplant center in the US. We included all recipients who had received kidney or kidney-pancreas transplants through robotic surgery between November 15th, 2022, and March 14th, 2023. We investigated the incidence of infection and its pathogen and the duration from transplant to infection for bacterial, fungal, and viral etiologies within 6 months post transplantation.

Results

Thirty-four, and 2 kidney and kidney/pancreas transplants were performed during the study period. Thirteen (36.1%) and 4 (11.1%) of urine culture positivity (predominantly Pseudomonas and E.coli) and bacteremia were identified. The causative pathogen of 4 bacteremia includes two Staphylococcus aureus, E.coli, and Morganella. Only 6/36 (16.7%) and 3/36 (8.3%) of clinically significant CMV and BK Polyomavirus DNAemia, which required treatment, including adjusting immunosuppression, were identified. Six cases of SARS-CoV-2 and one case of influenza were also identified.

Conclusion

We conducted a retrospective cohort study regarding infections after robotic kidney and kidney/pancreas transplant surgery. A very low surgical site infection and relatively low BK Polyoma viral infection rate were noted. Further study should be required to compare the incidence between robotic and traditional surgery.

Disclosures

Yoichiro Natori, MD, Eurofin/Viracor: Honoraria|Nobel Pharma: Advisor/Consultant
P-2287. Are Solid Organ Transplant or Hematopoietic Stem Cell Transplant Recipients at Greater Risks of Unfavorable Outcomes of Pneumocystis Pneumonia?
Authors: Winichakoon Poramed , Albasata Hanan , Poutanen Susan M , Hosseini-Moghaddam Seyed M
Published: January 2025

Background

Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients with Pneumocystis pneumonia (PCP) appear to be at risks of adverse outcomes and mortality with limited data.

Methods

In this retrospective cohort, we compared the PCP manifestations, including clinical presentation, laboratory data, imaging studies, treatment and outcomes between SOT and HSCT recipients diagnosed with PCP at University Health Network, Toronto, Canada, from January 2011 to January 2022. We measured a composite outcome including 21-day ICU admission and/or 28-day all-cause mortality following PCP diagnosis. Using multivariable logistic regression analysis, we estimated adjusted odds ratio (aOR) to determine the concurrent effects of covariates.

Results

During the accrual period, a total of 32 (55.2%) HSCT (20 allogeneic, 11 autologous, and one cord-blood transplant recipients) and 26 (44.2%) SOT (10 kidney, 8 liver, 5 lung, and 3 heart recipients) fulfilled the PCP diagnosis criteria. Notably, chronic steroid treatment was more common in SOT than in HSCT recipients [24 (92.3%) vs 13 (40.6%), p = 0.001]. The median time of post-transplant PCP diagnosis was 488 days with interquartile range (IQR) 90-481 in the HSCT group, and 1,453 (IQR 38-3,909) days in the SOT group. In comparison, dyspnea [25 (96.2%) vs 23 (71.9%), p = 0.015], desaturation [16 (72.7%) vs 12 (38.7%), p = 0.015], and pleural effusion [8 (30.8%) vs 2 (6.3%), p = 0.014] were more frequent in the SOT group. We observed a higher fungal load [11,450 (IQR 2,207-191,750) vs 10,295 (IQR 2,405-21,325) copies/mL, p = 0.043] and occurrence of the composite outcomes [13 (50%) vs 3 (9.4%), p = 0.001) in the SOT than the HSCT group. In the multivariable analysis, SOT recipients (aOR 7.1, IQR 1.3-37.4), patients received chronic steroid treatment (aOR 1.3, IQR 0.2-6.6), required supplemental O2 at the initial presentation (aOR 1.8, IQR 0.3-10.4), and had pleural effusion (OR 10.4, IQR 1.5-70.8) were significantly at the risk of composite outcome.

Conclusion

SOT recipients appear to be at a greater risk of ICU admission and mortality than HSCT recipients. SOT or HSCT recipients with pleural effusion or requiring supplemental O2 on admission, particularly if receiving chronic steroid therapy, are particularly at risk of severe outcomes.

Disclosures

All Authors: No reported disclosures
P-2291. Low-level CMV Viremia After Solid Organ Transplant: Should We Treat?
Authors: Goyal Rohan , Burack Daniel A , Orner Erika , Tow Clara , Alsunaid Sammar R , Rochlani Yogita , Kyriazis Periklis , Bartash Rachel , McCort Margaret E
Published: January 2025

Background

Cytomegalovirus (CMV) disease is known to affect morbidity and mortality after solid organ transplant (SOT). However, less is known concerning low-level CMV viremia (llCMV) (< 1000 IU/ml). Having llCMV and the decision to treat llCMV with antivirals may be associated with changes in long-term graft outcomes and mortality in SOT. We aimed to review patient-level outcomes of llCMV after SOT in our large urban academic medical center.

Methods

We performed a retrospective review of patients from Montefiore Medical Center who underwent heart, liver, lung, kidney, pancreas, or multi-visceral transplant between 2020-2021 and developed llCMV within 2 years of SOT. Chart review was performed to characterize how llCMV was managed and outcomes such as graft failure, graft rejection, rehospitalization, concomitant infections, and death relative to llCMV detection.Figure 1.Distribution of other infections affecting solid organ transplant recipients within 1 year of low level CMV viremia.

Results

Eighty-five adult SOT recipients who had CMV viral loads measured between 50 and 1000 IU/mL within two years of transplant were identified. See Table 1 for recipient details. The average time from transplant to llCMV was 272 days. Seventeen (20%) patients were receiving antiviral prophylaxis at the time of llCMV, while post-transplant CMV prophylaxis had been discontinued in 66 patients (78%) for an average of 149 days prior to llCMV. 64% (54/85) were started on antivirals or had an antiviral dose increase in response to llCMV, which was continued for an average of 109 days. Within a year of llCMV, 42 (49%) of SOT recipients were re-hospitalized. Forty-two (49%) of patients experienced non-CMV infections within 1 year of llCMV detection; see Figure 1. Graft rejection occurred in 25 (29%) of patients with llCMV, and 13 (15%) experienced graft failure. Mortality within 1 year of llCMV was 8% (7/85).

Conclusion

llCMV is likely a reflection of overall immune status and is often temporally associated with rehospitalization and concomitant infections. Graft rejection and death are uncommon in adult SOT recipients with llCMV within 2 years of transplant. Although antiviral use was common in response to llCMV, the benefit of this is unknown and comparison to outcomes of SOT recipients without llCMV or those not receiving therapy for llCMV is needed to better determine when treatment is needed.

Disclosures

All Authors: No reported disclosures
P-2309. Assessment of Risk Factors Associated with Subtherapeutic Posaconazole Levels
Authors: Garzia Christopher , Nelson Brian , Loo Angela , Demenagas Nicholas , Kubin Christine J
Published: January 2025

Background

There is significant variability in patient serum posaconazole levels, and it is unclear what characteristics increase the risk for subtherapeutic levels. Higher levels have been associated with improved outcomes. The purpose of this study is to identify risk factors associated with subtherapeutic posaconazole serum levels.

Methods

Retrospective study of adult patients admitted to NewYork-Presbyterian Hospital who received posaconazole with at least one level obtained at steady-state. Levels were obtained after at least five consecutive days of therapy with no interruptions > 24 hours or dosage changes prior to initial level. Patients were grouped based on if the initial level was therapeutic, defined as a serum level > 1 mcg/mL. Risk factor assessment was performed using a logistic regression model. Baseline characteristics between therapeutic and subtherapeutic groups were compared via chi-squared test for categorical variables and independent t-test for continuous variables.

Results

383 patients were included: 280 initial levels were therapeutic and 103 were subtherapeutic. Patients primarily consisted of those with solid organ transplant (48.8%) and hematologic malignancy (38.6%). Significant differences between therapeutic and subtherapeutic groups included median weight (73 vs 78 kg, p=0.017) and initial weight-based doses (4.4 vs 4.2 mg/kg, p=0.044), respectively. This prompted an exploratory analysis finding significant association with BMI > 35 (4.1% therapeutic vs 12.1% subtherapeutic, p=0.006). Initial dose thresholds of at least 3 mg/kg and 4 mg/kg showed nonsignificant increases in therapeutic levels (p=0.056 and p=0.107 respectively). On multivariable analysis, subtherapeutic levels were more likely in patients who are black or African American (OR 1.869, 95% CI 1.009, 3.465), had diarrhea (OR 1.978, 95% CI 1.149, 3.408), and had a BMI > 35 (OR 3.538, 95% CI 1.300, 9.628).

Conclusion

Patients who are Black or African American, have diarrhea, and have a BMI > 35 were identified as having increased risk for subtherapeutic levels at 300 mg daily dosing. Patients at risk may benefit from initial weight-based dosing of at least 4mg/kg, however this requires additional confirmatory studies.

Disclosures

All Authors: No reported disclosures
P-2310. Gammaproteobacteria Load Responses in the Intestinal Microbiota of Patients Undergoing Hematopoietic Cell Transplantation Predicts Resistant Gram-Negative Rod Colonization
Authors: Mortimer Leanne , Sénéchal Jaxon , Janusz Nicole , Carroll Amanda C , Yan Austin , Leite Tamara , Purssell Andrew , Kekre Natasha , Kennah Michael , Buchan C Arianne , MacFadden Derek
Published: January 2025

Background

Hematopoietic cell transplant (HCT) patients are at high risk of Gram-negative rod (GNR) blood stream infections (BSIs) particularly before pre-engraftment. Globally, breakthrough infections with resistant GNRs (rGNRs) are increasing in HCT while rGNR epidemiology has become increasingly complex to predict. It’s recognized that individualized antimicrobial HCT therapy is needed but it is unclear what screening strategies are optimal to detect rGNR colonization. Single taxon dominance of certain Gammaproteobacteria (ɣ-bacteria) species in HCT intestinal microbiomes is a BSI risk factor where colonizing strains present prior to transplant are predominant aetiologies of GNR BSIs. In this study we sought to understand how ɣ-bacteria loads respond to HCT antimicrobial therapy.

Methods

We performed a prospective study of 60 adult patients undergoing HCT at The Ottawa Hospital from 2021-2022. A baseline fecal sample collected < 1 week before conditioning was screened by culture for colonization with rGNR to fluoroquinolones (FQ), 3rd generation cephalosporins (3GC) and carbapenems. Total- and ɣ-bacteria loads were measured by qPCR in baseline and serial specimens until engraftment, expressed as the Log10 (ɣ-bacteria 16S copies / total 16S copies) per ng fecal DNA. Ceftriaxone (CTX) and piperacillin-tazobactam (TZP) are used for prophylaxis and empiric FN therapy, respectively at our institution.

Results

High ɣ-bacteria loads were associated with baseline rGNR colonization compared to no rGNR colonization (Log10 (-1.85) vs Log10 (-2.39), p < 0.0095) (Fig. 1). Highest loads occurred when resistant Escherichia coli or Klebsiella pneumoniae colonized the intestinal microbiota (Log10 (-1.34), p < 0.001). ɣ-bacteria loads were refractory to CTX and TZP therapy when colonizing E. coli or K. pneumoniae carried 3GC resistance (Fig. 2a). In contrast, ɣ-bacteria loads decreased > 2 Log10 in response to CTX and TZP if at baseline rGNRs were FQ resistant, expressed chromosomal AmpC, or if no rGNRs were detected (Fig. 2b, c, d).

Conclusion

ɣ-bacteria load measurement during HCT may be useful for predicting colonization with rGNR strains and identifying patients at risk of GNR BSI.

Disclosures

All Authors: No reported disclosures
P-2324. Detections of Endemic Coronaviruses in Medically Attended Respiratory Illness: Clinical Characteristics and Seasonal Trends from Two Public Health Surveillance Studies in Minnesota
Authors: Bastug Kristen , Martin Karen , Como-Sabetti Kathryn , Friedlander Hannah , Sanders Jeffrey , Brandstetter-Figueroa Izzy , Bistodeau Sarah , Strain Anna K , Vetter Sara , Lynfield Ruth , Thielen Beth K
Published: January 2025

Background

Human coronavirus (hCoV) strains OC43, NL63, HKU1, and 229E exist worldwide and have the potential to cause severe disease. Understanding hCoV seasonality, clinical symptoms, and risk factors for severe disease may help predict the impact of emerging respiratory viral pathogens.

Methods

Eighteen outpatient clinics submitted clinical data and respiratory specimens from patients with influenza-like illness between 2010-2023. Inpatient surveillance data was submitted from 3 hospitals (including one freestanding children’s hospital) between 2013-2018 from patients with acute respiratory illness. Respiratory specimens were tested using a multi-target real-time RT-PCR for 23 bacterial and viral respiratory pathogens.

Results

We tested 24,765 specimens (51.2% hospitalized, 48.8% outpatients) and identified 1,207 non-SARS-CoV-2 coronavirus-positive cases (42% hospitalized, 58% outpatient). 74% of inpatient cases were submitted by a standalone children’s hospital. For hCoV+ cases the median outpatient age in years was 36.5 and inpatient age was 0.6. All hCoV strains were detected at higher frequency during the winter months (Figure 1) and sequential winter seasons demonstrated different dominant strains of hCoV (Figure 2). hCoV was co-detected with other viral pathogens in 29% of cases but strains were not co-detected with each other (Figure 3). The median age for cough, diarrhea, fever, URI symptoms, seizure, vomiting and wheeze was ≤1.0 years, while headache, myalgia, and sore throat was 27-31 years (Figure 4). Among hospitalized children with only hCoV detected, comorbidities included neurologic disorder(22%), developmental delay(14%), seizure disorder(14%), cardiovascular disease(13%), prematurity(12%), and asthma(10%). 16% required mechanical ventilation, 27% required ICU admission, and 41% received antiviral therapy. Patients with hCoV+1 other pathogen compared to those with singular hCoV+ infection did not have an increased risk for ICU admission or mechanical ventilation.

Conclusion

hCoV circulation in Minnesota demonstrates temporal variation in dominant hCoV strain. hCoV infection may present with different symptoms according to the patient’s age. hCoV may contribute to severe respiratory disease in the absence of other pathogenic viruses.

Disclosures

Beth K. Thielen, MD, PhD, GSK: Honoraria|Merck: Grant/Research Support|Sanofi: Honoraria|Seegene: Honoraria
P-2338. Global surveillance of human Metapneumovirus (hMPV) and Respiratory Syncytial Virus (RSV) epidemiology since 2022
Authors: Billard Marie-Noelle , Wildenbeest Joanne G , Braas Olivier , Schneijdenberg Rob , Rodgers-Gray Barry , Fullarton John , Bont Louis J
Published: January 2025

Background

Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are common respiratory pathogens. Whilst the seasonality of RSV is well-documented, less is known about the epidemiology of hMPV and the global impact of the SARS-CoV-2 pandemic on both viruses. The objective of this study was to monitor the real-time temporal and geographic distribution patterns of hMPV and RSV over two seasons.

Methods

A global surveillance dashboard using publicly available outputs of (sub-)national clinical or laboratory-based surveillance data was developed in 2022. Twenty-six countries from both hemispheres were included, based on the availability and consistency of surveillance data for both viruses. For each country, data were extracted on the weekly number of hMPV- or RSV-positive cases and the weekly positivity rate (cases/total tested).

Results

From Jan-22­, hMPV and RSV circulated globally with seasonal patterns in most geographic regions. The hMPV season was typically observed in winter and spring, following the RSV season in autumn and winter. There was some overlap between the hMPV and RSV seasonal epidemic curves in most countries. The number of cases and the peak positivity rate were generally lower for hMPV than RSV. However, not all countries fit these patterns: hMPV can circulate year-round in tropical countries, and RSV peaked particularly early in East Asia, with a second peak in the spring and summer. While these data suggest a trend for both hMPV and RSV to return to pre-pandemic seasonality, there was residual displacement of the timing of the peaks in multiple countries.

Conclusion

hMPV and RSV displayed seasonal patterns in most countries with an evolving return to pre-pandemic seasonality. Continued surveillance is required to confirm this trend during the coming season to better understand the dynamics of hMPV seasonality.

Source of funding: Funded by Icosavax, a member of the AstraZeneca Group. All authors contributed to the development of the publication and maintained control over the final content.

Disclosures

Barry Rodgers-Gray, n/a, AstraZeneca: Employer has received payment from AstraZeneca for work on various projects outside the scope of this study|Sanofi: Employer has received payment from Sanofi for work on various projects outside the scope of this study John Fullarton, n/a, AstraZeneca: Employer has received payment from AstraZeneca for work on various projects outside the scope of this study|Sanofi: Employer has received payment from Sanofi for work on various projects outside the scope of this study
P-2354. Neonatal Enterovirus and Parechovirus Infections—National Enterovirus Surveillance System, United States, 2004–2022
Authors: Delahoy Miranda , Getachew Halle , English Randall , Kidd Sarah
Published: January 2025

Background

Enteroviruses (EV)—a group of viruses including echoviruses (E) and coxsackieviruses (CV)—and parechoviruses (PeV) can cause a range of symptoms, including respiratory illness; hand, foot, and mouth disease; acute flaccid myelitis; meningitis; and sepsis. Neonates (persons < 1 month old) are at higher risk of severe EV or PeV disease. We analyzed data from the National Enterovirus Surveillance System (NESS) to assess types and outcomes of neonatal EV and PeV infections reported during 2004–2022.

Methods

NESS is a passive, laboratory-based surveillance system that collects reports of positive EV and PeV virus type results in the United States. We analyzed data on EV and PeV specimens collected during January 1, 2004–December 31, 2022. Outcome data (defined as whether the patient died) were reported to NESS during 2014–2022. Chi-squared tests were used to compare virus type frequencies by age, with differences considered significant if p < 0.05.

Results

Overall, 10,833 EV and PeV infections were reported during 2004–2022: 9,197 (85%) had reported age, of which 753 (8%) were among neonates. Among 631 neonatal EV or PeV infections with identified virus type (84%), Coxsackievirus type B5 (CVB5) (76; 12%), CVB3 (64; 10%), PeVA3 (61; 10%), E11 (54; 9%), and CVB4 (52; 8%) were detected most frequently. Compared with persons ≥ 1 month old, CVB types 1–5, PeVA3, and E11 were significantly more likely to be detected among neonates, whereas EV-D68 and E30 infections were less common. Among 483 neonates with EV or PeV infections during 2014–2022, 68 (14%) had known outcome, of whom 16 (24%) died.

Conclusion

EV and PeV infections can cause severe disease among neonates. The frequencies of EV and PeV virus types detected among neonates differ from those among persons ≥1 month old, although this may partially reflect testing differences by age. Assessing mortality among neonates with EV and PeV illness is limited by incomplete outcome data and lack of systematic EV and PeV testing and reporting, which may be biased toward including patients with more severe illness. Strengthening capacity for EV and PeV testing, typing, and surveillance would be beneficial for understanding the disease burden among neonates and informing treatment options and prevention measures.

Disclosures

All Authors: No reported disclosures
P-2357. Respiratory Syncytial Virus (RSV) Disease Burden among Adults in Primary Care Settings in High-income Countries: a Systematic Review and Modelling Study
Authors: Li You , Kenmoe Sebastien , Begier Elizabeth , Wahi-Singh Pia , Wahi-Singh Bhanu , Liang Caihua , Sato Reiko , Gessner Bradford D , Nair Harish
Published: January 2025

Background

Data on RSV disease burden in adults remain scarce and mostly focus on hospitalisation. We aimed to estimate RSV disease burden in primary-care settings among adults in high-income countries.Figure 1.PRISMA flowchart

Methods

We conducted a systematic review to include studies that reported RSV disease burden in primary-care settings; studies of emergency department (ED) visits were also included but analysed separately. We searched MEDLINE, Embase, Global Health, CINAHL, Web of Science, and Global Index Medicus for eligible studies published between 1 Jan 1996 and 30 Nov 2022 and conducted citation searching of identified studies. Using a random-effects meta-analysis, we synthesised RSV incidence rate, positive proportion, and incidence-to-hospitalisation ratio. When estimating RSV incidence rate and positive proportion, we adjusted for RSV under-ascertainment related to clinical specimens and diagnostic tests used in individual studies by a previously published two-stage statistical framework. We used the Joanna Briggs Institute critical appraisal checklist for assessing study quality.

Results

We included 14 studies (Figure 1), with 13 studies rated as high-quality. RSV incidence rate increased with increasing age in primary-care settings and in ED; the adjusted annual incidence rate in primary-care settings ranged from 2,350 (95% CI: 1,254–4,405) per 100,000 in 18–49 year-olds to 4,339 (3,267–5,763) in adults ≥65 years (Table 1). The RSV positive proportion in acute respiratory infection episodes in primary-care settings was higher among those aged ≥65 years than 18–49 years (Table 2). In adults ≥65 years, 6.2% (1.4–23.8) of RSV episodes in primary-care settings led to hospitalisation, equivalent to one patient progressing to hospitalisation for every 16 outpatient visits. According to five studies (total N=413; age: >60 or >65 years), no RSV-associated deaths occurred in primary-care settings.

Conclusion

RSV disease burden in primary-care settings is substantial among adults in high-income countries, particularly for older adults. Further larger studies are needed to assess mortality risk following RSV-related outpatient visits. This study’s estimates have important implications for evaluating RSV prevention programmes’ impact.

Disclosures

You Li, Pfizer: Advisor/Consultant Elizabeth Begier, MD, M.P.H., Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds (Private Company) Caihua Liang, MD, PhD, Pfizer: Stocks/Bonds (Private Company) Reiko Sato, PhD, Pfizer Inc: employee|Pfizer Inc: Stocks/Bonds (Private Company) Bradford D. Gessner, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Harish Nair, n/a, Pfizer: Advisor/Consultant
P-49. Sexual and Gender Minority Veterans With HIV More Likely Vaccinated Against HPV Than Those Without HIV in a Nationwide Cohort
Authors: Van Epps Puja , Meriwether Wyatt E , Matza Alexis (Lexi) , Mcconnell Alex , Shipherd Jillian , Kauth Michael R
Published: January 2025

Background

Certain sexual and gender minority (SGM) adults, particularly those with HIV, experience a disproportionate impact of Human Papillomavirus (HPV) and its related diseases. Vaccination against HPV, which is recommended in all adults up to age 26 and in some up to age 45, is an important tool in addressing this disparity. In non-Veteran cohorts, young SGM adults, particularly of non-White race are less likely to be vaccinated against HPV. We examined HPV vaccination rates in the Veterans Health Administration (VHA) among a nationwide cohort of age eligible SGM Veterans and report on disparities across racial groups and HIV status

Methods

We queried VHA’s national database to identify Veterans whose sexual orientation is recorded as lesbian, gay, bisexual or queer (LGBQ+) and gender identity as transgender woman (TGW) as of April 2024. Birth sex male LGBQ+ and TGW Veterans of both birth sexes were included in the cohort, stratified by age, race/ethnicity and HIV status. Within these cohorts we quantified receipt of HPV vaccine doses in the VHA starting 2022 and compared rates of vaccine initiation or completion across groups.

Results

Among the 1802 LGBQ+ males age 26 and under, 561 (31%) had received at least one dose of the HPV vaccine in the VHA; of these, 50% had completed the series (Figure 1). In the 27-45 age group, 2082/14863 (14%) had initiated and of these, 60% had completed the series. Non-Whites in both age groups had higher rates of series initiation compared with Whites (19-26: 34% vs. 30%; 27-45: 17% vs. 11%) (Figure 2). Those with HIV had higher rates of series initiation in both age groups compared to those without (19-26: 52% vs. 30%; 27-45: 26% vs. 16%) (Figure 3). Among TGW: 26 and under (n=154), 21% had received at least one dose and 38% of these have completed the series; 27-45 (n=932) 9% had initiated the series, but rates were much higher in those with HIV in this group (series initiation: 33%; completion rate: 63%).

Conclusion

Less than a third of eligible SGM Veterans have received HPV vaccination in the VHA. Unlike non-Veteran cohorts, younger age and non-White race were associated with increased vaccination rates, with rates among those with HIV being the highest and those among TGW the lowest. More efforts are needed to increase HPV vaccination in these high need populations.

Disclosures

All Authors: No reported disclosures
P-55. Knowledge of Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women: A survey among Healthcare Professionals
Authors: Santoyo Leticia , López Karina , Martínez-Reséndez Michel F , Aguirre-García Gloria Mayela , Garza Erick
Published: January 2025

Background

Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory tract infection (RTI), playing a significant role in infant mortality under six months of age, especially in low and middle-income countries. In August 2023, the U. S. Food & Drug Administration approved active immunization of pregnant women between 32 to 36 weeks gestational age for the prevention of lower RTI and severe lower RTI caused by RSV in infants up to 6 months of age.

Figure 1.

Distribution of responses according to medical specialt

Methods

An electronic survey comprised of 18 questions was administered to primary care physicians, internists, gynecologists, and pediatricians. The survey included 4 items to gather participant characteristics, 1 addressing general vaccination recommendations during pregnancy, 5 covering general aspects of the RSV vaccine, 7 focusing on knowledge of the RSV vaccine during pregnancy and 1 item to ascertain whether they recommend this vaccine. If participants lacked prior knowledge of the vaccine or its use in pregnant patients, the survey was concluded

Figure 2.

Previous Knowledge of RSV Vaccine by Medical Speciality

Results

168 responses were received, the distribution by specialties is shown in Figure 1. A total of 76/168 doctors (45.2%) were aware of the existence of a vaccine against RSV (Figure 2), 52/76 (68.4%) had knowledge of the vaccine targeted to pregnant women (Figure 3). Among the doctors familiar with this vaccine, 29/52 (55.8%) knew that it is a single-dose vaccine. Additionally, 28/52 (53.8%) were aware of when it should be administered, 31/52 (59.6%) knew it is a seasonal vaccine and 27/52 (51.9%) were previously aware of its efficacy in providing protection to infants up to 6 months old. Furthermore, 100% of the surveyed expressed that they would recommend the vaccine once it is approved in Mexico

Figure 3.

Previous knowledge of the vaccine targeted to pregnant women

Conclusion

Only 27/168 (16%) of the surveyed demonstrated a satisfactory knowledge about the RSV vaccination in pregnant women, including details such as dosage, indication, timing of administration and efficacy.

These surveys serve to assess physicians knowledge on the topic under study, and are valuable educational tools for the respondents by provifing information and reliable sources for further reading of the topic. Nevertheless our findings highlight the need for additional comprehensive educational campaigns targeting healthcare providers

Disclosures

All Authors: No reported disclosures
P-57. Durability of SARS-CoV-2 specific Cellular Immune Response after COVID-19 Vaccination in PLWH
Authors: Sehgal Amit , Nischal Neeraj , Ranjan Sanjay , Mahishi Niranjan , Jorwal Pankaj , Wig Naveet , Grover Pragati , Khan Maroof a , Awasthi Amit , Binayke Akshay
Published: January 2025

Background

People living with HIV (PLWH) face the dual challenge of human immunodeficiency virus(HIV) infection and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. It is associated with severe outcomes and a higher risk of mortality.

In January 2021, the vaccination campaign against SARS-CoV-2 was launched in India and started mass administration of two types of vaccines. The two vaccines used on a large scale were, a recombinant, replication-deficient chimpanzee adenovirus vectored vaccine/ ChAdOx1 nCoV-19 (Covishield) and whole virion inactivated vaccine/ BBV152 (Covaxin).The study of cellular immune responses to COVID-19 vaccination in PLWH was vital for safeguarding this vulnerable population.

Methods

Study design: Prospective observational study

Study population: The individuals recruited in the study were vaccinated with at least 2 doses and/or booster dose of the COVID-19 vaccine (COVISHIELD/COVAXIN). The individuals were segregated into two groups (PLWH and non-HIV-infected healthy individuals).

Testing Method: Peripheral blood mononuclear cell (PBMC) were cultured to test the SARS-CoV-2-specific T cell immune response using activation induced marker/ intracellular cytokine staining (AIM/ICS) assay.

Distribution of CD4 T lymphocytes count in HIV patients with mean CD4 count 470 cell/µl.

Results

We conducted did this study in two phases. The first phase was conducted between August 2022 and December 2022, while the second phase, or the follow-up, took place from January 2023 to December 2023. In the first phase/ first visit (V1), we recruited 50 adult PLWH and 40 adult healthy controls. Subsequently, in phase 2/follow-up/ second visit (V2), we achieved a follow-up rate of 100% in each arm.

SARS-CoV2-specific cellular immune response after COVID-19 vaccination was comparable and durable IN PLWH as compared to healthy controls.

Conclusion

Comparable and durable immune response was observed in PLWH population on regular highly active antiretroviral therapy (HAART), with stable viral suppression and good CD4+ T cell counts. This was consistent over time across 1 year gap in both phases of the study and across different vaccine types. This outcome indicates that the cellular immune responses in our PLWH cohort is comparable and durable to that of the general population, which is a reassuring finding for the public health.

SARS-CoV-2-specific CD8 T-cell immune response (scatter plots displaying the results of CD8 T cell assays, specifically evaluating the production of various cytokines (IFNγ (Interferon-gamma), TNFα (Tumor Necrosis Factor-alpha), and IL-2 (Interleukin 2), Granzyme B (Gran-B) at two different time points V1 and V2 (visit 1 and visit 2) with p values mentioned at the top.

Disclosures

All Authors: No reported disclosures
P-79. Racial/ethnic disparities and facility-level variation in major lower limb amputation among patients with a new diagnosis of diabetic foot ulcer within the Veterans Health Administration
Authors: Suzuki Hiroyuki , Vaughan-Sarrazin Mary , Ohl Michael , Mecham Bradley , Mccoy Kimberly , Livorsi Daniel J
Published: January 2025

Background

Diabetic foot ulcers (DFU) are associated with high morbidity and mortality, including major lower limb amputation (LLA). Little is known about racial/ethnic disparities and facility level variation in major LLA in large healthcare systems, such as Veterans Health Administration (VHA). VHA cares for over 9 million Veterans in 140 facilities with no insurance-related barriers to care.Figure:Caterpillar plot of relative odds of major LLA in each medical center

Methods

This is a retrospective cohort study of all Veterans with a new diagnosis of DFU during 2016-2021. The outcome was major LLA within 12 months from DFU diagnosis. We conducted multivariable logistic regression with random facility intercepts to assess variation in major LLA across VHA facilities while adjusting for patient demographics, comorbidities, and the severity of DFU at initial diagnosis. We calculated odds ratios (ORs) and confidence intervals (CIs) for associations between patient-level variables and major LLA. We calculated the median OR (MOR) as a measure of facility-level variation in major LLA. The MOR can be interpreted as the median change in odds of major LLA associated with care in all pairs of facilities.

Results

There were 105,644 patients from 140 hospitals in the cohort. The median age was 67. Most patients were White (75.6%), followed by Black (18.5%) and Hispanic (6.0%). At presentation, 91.6% had an early-stage ulcer while the rest had complicated DFU. Major LLA occurred in 4055 patients (3.8%). In the logistic regression model, variables associated with higher odds of major LLA were Black (OR 1.77, 95%CI 1.62-1.92), Native American (OR 2.08, 95%CI 1.57-2.75), Hispanic (OR 1.38, 95%CI 1.19-1.60), complicated DFU (OR 3.36, 95%CI 3.11-3.64), chronic kidney disease (OR 1.11, 95%CI 1.01-1.21), peripheral vascular disease (OR 3.49, 95%CI 3.24-3.76) and myocardial infarction (OR 1.32, 95%CI 1.21-1.49). The facility-level variation in major LLA (MOR: 1.87, p< 0.001) was larger than most of patient-level risk factors, suggesting that facility-level factors play an important role in the outcome of DFU.

Conclusion

Our study showed racial/ethnic disparities and facility-level variation in major LLA within the VHA. Future studies should investigate the reasons for this variation and develop strategies for reducing disparities in LLA.

Disclosures

Daniel J. Livorsi, MD, Merck: Grant/Research Support