bluuebunny/crossref_metadata_2025 huggingface dataset:
329. Vancomycin area under the concentration-time curve monitoring from Bayesian modeling in outpatient parenteral antimicrobial therapy
Authors: Gillett Eric M , Aleissa Muneerah M , Pearson Jeffrey C , Kubiak David W , Dionne Brandon , Chan Brian T
Published: November 2023

Background

Current vancomycin monitoring guidelines recommend area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) monitoring for patients with serious MRSA infections. Most AUC monitoring studies have included hospitalized patients only; however, many patients complete vancomycin therapy in the outpatient setting. While traditional two-level AUC calculations are logistically challenging for outpatients, Bayesian modeling software can allow for single level AUC estimations. There are sparse data on the feasibility, safety, and efficacy of vancomycin AUC monitoring in OPAT.

Methods

We conducted a single-center, quasi-experimental, interrupted time series study of adult patients enrolled in the OPAT program at our institution for vancomycin management. Our institution implemented a pharmacist-driven vancomycin monitoring program using AUC targets from September 8th, 2019 to February 25th, 2020, and again from September 25th, 2022 to March 16th, 2023. Patients enrolled in the monitoring program underwent vancomycin monitoring using an AUC goal of 400-600 mg*hr/L, estimated using Bayesian modeling. A cohort comprising all patients enrolled in the OPAT program from July 4th, 2021 through August 27th, 2022 for trough only vancomycin monitoring was used for comparison. Patients were excluded from analysis if they were undergoing renal replacement therapy at baseline, enrolled in OPAT for ≤ 72 hours, or did not have vancomycin levels drawn for ≥ 14 days. The primary outcome was nephrotoxicity defined as a serum creatinine increase by ≥ 0.5 mg/dL or ≥ 50% during outpatient vancomycin therapy.

Results

There were 63 patients in the AUC arm, and 60 patients in the trough-only arm. The incidence of nephrotoxicity was lower in the AUC cohort (6.3% vs 23.3%, p=0.01). There was no difference in other vancomycin-related adverse event rates (1.6% vs 10.0%, p=0.06). Vancomycin discontinuation due to adverse event was lower in the AUC arm (6.3% vs 20.0%, p=0.03).

Conclusion

Patients undergoing AUC monitoring were significantly less likely to develop nephrotoxicity during outpatient vancomycin treatment. Bayesian modeling represents a viable and safe option for vancomycin AUC monitoring in OPAT.

Disclosures

David W. Kubiak, PharmD, BCPS, BCIDP, FIDSA, Astellas Pharma, Inc.: Advisor/Consultant|AVIR Pharma Inc: Advisor/Consultant|Cidara Therapeutics: Advisor/Consultant|Shionogi Inc: Grant/Research Support
341. Attitudes and Experiences of Individuals Approached to Participate in a Randomised, Placebo-Controlled, Feasibility Study of Encapsulated Faecal Microbiota Transplantation (FMT) for the Eradication of Gastrointestinal (GI) Carriage of Antibiotic Resistant Organisms (ARO): a Nested Qualitative Study
Authors: Merrick Blair , Prossomariti Désirée , Kertanegara Michael , Wyatt David , Goldenberg Simon D
Published: November 2023

Background

We undertook a single-centre, randomised placebo-controlled study to assess feasibility of eradicating GI carriage of ARO using encapsulated, lyophilised FMT – FERARO – IRCTN reg. no. 34467677. To aid design of future substantive trial, a nested qualitative study collected participant experiences and perceptions.

Methods

A subset (n=24) of recruited participants were approached and 13/24 (54%) participated in one of two 2-hour in-person semi-structured focus groups during, or shortly after completion of, their 6-month study follow-up. Additionally, where given, reasons for non-participation in approached eligible individuals were collected (n=110). Qualitative data underwent thematic analysis; initial coding and theme identification were undertaken by 2 trial researchers independently before further analysis in collaboration with third independent qualitative researcher.

Results

Four central themes were identified; (i) barriers to, and (ii) drivers of, trial participation, (iii) participant randomised controlled trial experience, and (iv) support of future research projects. Participation was influenced by physical ability and time availability to complete study related activities, prior treatment journey and experiences, as well as ongoing available treatment options, and altruism - a willingness to give back to the National Health Service (NHS). Importantly, neither the Covid-19 pandemic, nor lack of acceptability (‘yuck’ factor) of encapsulated lyophilised FMT, were identified as barriers to participant recruitment. FMT was well tolerated, and an intervention that participants viewed as ‘natural’ when compared to other medical treatments. Participants reported that both physical and mental health and/ or health behaviours improved as a result of trial participation, regardless of treatment allocation.

Themes, subthemes, and their relationships.

Conclusion

The frequency of face-to-face hospital-based study appointments presented a barrier to study participation, particularly for less mobile, more comorbid patients – a cohort that may benefit the greatest from participation. Substantive trial recruitment may be incentivised by the use of remote and/ or home visits including for investigational medicinal product (IMP) administration.

Disclosures

Simon D. Goldenberg, FRCPath, MD (Res), PGDipID, DipHIC, MSc, EnteroBiotix: Honoraria|Tillotts Pharma UK: Honoraria
342. Evaluation of Patient Satisfaction with Outpatient Parenteral Antibiotic Therapy (OPAT) at a University Medical Center
Authors: Sawey Ciara , Munsiff Sapan A , Burgoyne Colleen
Published: November 2023

Background

With the expansion of OPAT care over recent years, new devices such as elastomeric balls have been added to the available drug delivery options, which also include syringe, electronic pumps and gravity bags. The primary objective of this study was to evaluate the experience of patients (and their caregivers) on OPAT, ease of use with various delivery methods, and barriers to outpatient care.

Methods

The survey included questions on IV antibiotic received, delivery method, who administered the medicines, effect on daily activities, ease of access to staff, and thoughts on various aspects of the process and experience. Questions were multiple choice, based on Likert scale, or open-ended. Patients were recruited in person during infectious diseases (ID) clinic visits, or by phone, just before or around the time OPAT ended.

Results

We had 51 responses from 130 patients from 10/1/22 thru 3/31/23. Median age group was 55-64 years, 45% were women, for 78% it was first OPAT episode, and 23% received > one IV drug. Syringe push was used for 37%, elastomeric ball for 38%, gravity bag for 18% and electronic pump for 7% of agents. Most (76%) received help in administering treatment by friend or family (spouse=75%). 44% of infusions were once/day and 27% were 3 or more times/day. Home nursing services were received by 94% (5 different agencies) and > 6 different infusion pharmacies supplied the medicines. Medicine was always delivered on time for 38 of 45 respondents.

All patients found IV push and elastomeric ball easy to use; 25% disagreed with this about gravity bag or electronic pump. Overall satisfaction was 94% with OPAT course and 94% felt instructions on how to administer medicines at home were clear and easy. Financial hardships were noted by 9 of 48 respondents (12 responded “neutral”) and 77% had to curtail some or most of their daily activities while on OPAT.

Conclusion

Overall, patients’ responses were positive of our OPAT program. However, the large portion of patients needing to curtail their usual activities highlights the need for more study on how regimen details such as delivery device and infusion frequency impact patient and caregiver experience. Financial hardships may be underestimated as final bills may not yet have been received by patients.

Disclosures

All Authors: No reported disclosures
344. Evaluation and Comparison of the Complex Outpatient Oral Antibiotics Therapy (COPAT) Program vs Oral Parenteral Antibiotic Therapy (OPAT) Program at West Virginia University (WVU) Medicine Healthcare System
Authors: Okunlola Ololade O , Pizzuti Vincenzo J , Johnson Jessica , Juskowich Joy J , Sarwari Arif R , Reece Rebecca
Published: November 2023

Background

Patients with severe infections often require several weeks of antibiotic therapy. Outpatient Parenteral Antibiotic Therapy (OPAT) services decrease hospital length of stay, incidence of hospital-associated infections, healthcare costs, and increase patient recovery rates. Complex outpatient oral antibiotics therapy (COPAT) is an alternative to OPAT that transitions patients to appropriate and equally efficacious oral antibiotics. While there is extensive body of literature on OPAT, there is a paucity on COPAT. We aimed to examine the COPAT program at WVU Medicine, particularly patient demographics and clinical outcomes, and compare these to OPAT.

Methods

This was a retrospective chart review of patients enrolled in COPAT and OPAT program between January 2021 to May 2022 at WVU Medicine, excluding patients who switched cohorts. From the electronic health record, both demographic and clinical variables were extracted. Descriptive analyses were done comparing demographics and clinical outcomes of OPAT, COPAT and non-intravenous drug use (IVDU) COPAT patient groups. Inferential analysis is currently underway.

Results

A total of 334 charts were reviewed with 55% in OPAT program and 45% in COPAT. Demographic differences included younger age, higher tobacco and IVDU, and fewer other co-morbidities in COPAT group (Table 1). Separate analysis of non-IVDU COPAT found a similar trend of younger with fewer co-morbidities. The most common infection across groups was septic arthritis, comprising around 13% (OPAT) and 20% (COPAT) of cases. However vertebral osteomyelitis and endocarditis were higher in COPAT cohorts. Outcome findings were increased length of stay in COPAT but reduction in readmission rates compared to OPAT cohort. Increased safety interventions (22%) in OPAT compared to only 7% in COPAT, mostly due to acute kidney injury and myelosuppression. (Table 2)

Demographics and Infection Types Seen in OPAT, COPAT and Non-IVDU COPAT Patients.

Clinical Outcomes and Adverse Events observed in OPAT, COPAT and Non-IVDU COPAT Patient Groups.

Conclusion

This study demonstrated that COPAT is a suitable treatment option for both IVDU and non-IVDU patients with decreased rates of readmission and safety interventions and with lower rates of severe adverse events. While selection bias may explain differences in risk factors between OPAT and COPAT, the large variance in readmission and safety intervention rates suggests a possible causal relationship.

Disclosures

All Authors: No reported disclosures
364. Novel Polygalacturonic and Caprylic Acid (PG+CAP) Antimicrobial Wound Ointment is Effective in Managing Microbially Contaminated Chronic Wounds in a Pilot Prospective Randomized Clinical Study
Authors: Hachem Ray Y , Hakim Christopher , Dagher Hiba , Samaha Roula , Hammoudeh Diya' , Hamerschlak Nelson , Nasr Janane , Rosenblatt Joel , Jiang Ying , Chaftari Anne-Marie , Ghanem Odette , Ibrahim Amir , Bizri Abdul Rahman , Raad Issam I
Published: November 2023

Background

The use of antibiotics and antiseptics in the management of biofilm colonized chronic wounds is not fully effective in eradicating multidrug-resistant organisms. We developed PG+CAP ointment combining naturally derived agents commonly used in skin care and showed in our in vitro study that PG-+CAP combination ointment could rapidly eradicate gram positive, gram negative and fungal organisms embedded in biofilm within 1 hour. Furthermore, in a full thickness, microbially contaminated swine wound model study we found that with daily ointment application, PG+CAP ointment was significantly better at healing wounds at 2 weeks compared to MediHoney and was also significantly better at eradicating microbes colonizing wound tissues. In this current pilot human study, we compared PG+CAP ointment to MediHoney at three international centers.

Methods

This is a multicenter prospective randomized open label comparative study where patients with chronic full-thickness wounds at three academic international medical centers (American University of Beirut and Lebanese American University, Lebanon and Albert Einstein Medical Center, Brazil) were randomized to a daily treatment with either PG+CAP ointment or MediHoney. Clinical and wound assessments were obtained weekly up to 6 weeks. Full improvement was defined as 50% or greater decrease in wound size and/or a 75% or greater re-epithelialization and granulation of the wound with no necrosis or related adverse events (AEs) or sepsis. The validated Pressure Ulcer Scale for Healing (PUSH) score was used to track wound healing.

Results

A total of 20 patients with chronic wounds were included (10 patients in each arm). Age and clinical characteristics were comparable in both groups. Diabetes mellitus tended to occur more frequently in the PG+CAP arm (See Table 1-P=0.06). Full improvement/healing occurred in all patients (100%) randomized to PG+CAP with no AEs vs 70% full improvement in the MediHoney arm. Patients who received PG+CAP had more than two-fold wound improvement in terms of their PUSH scores compared to MediHoney:Table 1.Characteristics & Outcomes

Conclusion

Based on preliminary data from this prospective randomized multicenter trial, PG+CAP is safe and possibly more effective in achieving full improvement of chronic contaminated wounds when compared to MediHoney.

Disclosures

Joel Rosenblatt, PhD, Novel Anti-Infective Technologies, LLC: Licensed Technology Issam I. Raad, Distinguished Professor, Novel Anti-Infective Technologies, LLC: Technology License
372. Co-Administration of OVX836, NP-Based Universal Influenza Vaccine Candidate, with Conventional HA-Based Influenza Vaccine: Results of Phase 2a Clinical trial
Authors: Willems Paul , Tourneur Jessika , Guyon-Gellin Delphine , Le Vert Alexandre , Nicolas Florence
Published: November 2023

Background

Quadrivalent Inactivated Influenza Vaccine (QIV) generate antibody responses mostly directed against the highly mutating hemagglutinin. An alternative path for influenza vaccination is to generate cellular immunity to well-conserved nucleoprotein (NP), which has been associated with protection against influenza disease.

OVX836 is an unadjuvanted recombinant vaccine targeting NP. We have previously shown that OVX836 induces strong, dose-dependent NP-specific T and B-cell immune responses in human, with a signal for efficacy of 84% (95%CI=17%-97%), together with synergistic protection with QIV in preclinical models.

Here, we investigate in human the concomitant administration of OVX836 with QIV.

Methods

Phase 2a, randomized, double-blind, controlled, study to evaluate immunogenicity and safety of the concomitant administration of OVX836 and QIV in healthy adults (18-55 years) as 2 separate injections into the same arm, compared to (i) QIV and (ii) OVX836.

Results

Safety: All three treatments were safe and well tolerated. All occurrences of local and/or systemic signs and symptoms were mild or moderate in severity, except for one severe fatigue and myalgia in the QIV group and one severe headache in the OVX836 group.

Immunogenicity: Primary endpoint was achieved for the QIV and the OVX836+QIV, which triggered adequate immune response to the QIV (Hemagglutination Inhibition - HAI). Geometric mean fold-rise at Day 29 vs Day 1 of the HAI were similar between the QIV and OVX836+QIV groups for all strains contained in the QIV (figure 1). While there was an increase in NP-specific T-cell IFN-γ ELISPOT response at Day 8 for the OVX836 and the OVX836+QIV groups compared to QIV (p< 0.0001, Wilcoxon rank-sum test), no significant difference was observed in terms of change (D8-D1) between OVX836 and OVX836+QIV – figure 2.

The analysis of additional NP-specific immune parameters supports similar conclusion, with no to very limited immune interference between vaccines.Figure 1:Geometric Mean Ratio of HAI for each strain of the QIV between D1 and D29Figure 2:Mean Change (+Standard Deviation) of IFNg ELISpot response b/w D1 and D8

Conclusion

OVX836 co-administered with QIV was safe, with no immune interference on either HAI or NP-specific IFN-γ ELISPOT, thus warranting further evaluation in larger trials.

Disclosures

Paul Willems, n/a, Osivax: Advisor/Consultant Jessika Tourneur, n/a, Osivax: Stocks/Bonds Delphine Guyon-Gellin, n/a, Osivax: Stocks/Bonds Alexandre Le Vert, Osivax: Board Member|Osivax: Stocks/Bonds Florence Nicolas, n/a, Osivax: Stocks/Bonds
373. An open-label 24-week randomised multicentered clinical trial of Bictegravir/Emtricitabine/Tenofovir Alafenamide compared to Tenofivir/Lamifuvine/Efavirenz as an initial regimen in Chinese late presenters with HIV-1 infection
Authors: Qin Ling , Lu Ruichao , Wang Rugang , Zhou Yingquan , Wei Hongxia , Ma Ping , Zhang Junyan , Lyu Wei
Published: November 2023

Background

Despite tremendous efforts, late presenters (CD4 ≤ 350 cells/μl) still account for a staggering proportion of HIV patients at the time of diagnosis. The main objective of this study was to evaluate the viral-immunological efficacy of bictegravir/emtricitabine/ tenofovir alafenamide (BIC/FTC/TAF) in treatment-naïve, late presenters in Chinese patients with HIV-1 infection, comparing with national free tenofovir disoproxil fumarate/lamivudine/efavirenz/(TDF/3TC/EFV).

Methods

We conducted an open-label, randomized controlled trial at six HIV care centers in China, starting recruitment from June 2021 to December 2022. All treatment-naïve late presenters were randomised to receive TDF/3TC/EFV (group A) or BIC/FTC/TAF (group B). Serum HIV loads and CD4 cell counts were measured at baseline, 4 weeks, 12 weeks, and 24 weeks. The proportion of HIV-RNA < 50 copies/ml at 12 weeks was considered the primary endpoint and changes in viral loads and CD4 cell counts at other time points were secondary outcomes in PP and ITT analysis.

Results

We enrolled 200 late presenters, randomizing to group A (n=99) and group B (n=101). As of April 2023, 178/200 (89%) and 156/200 (78%) of randomized individuals completed 12 weeks and 24 weeks of follow-up. The study groups (n=200) were similar at baseline with a mean age of 43.0±13.8 years, 83.5% men, HBV co-infection percentage of 4%, HCV co-infection percentage of 2.5%, HIV viral load of mean 4.7±0.7 log copies/ml and CD4 cell counts of mean 109±74 cells/μl (Table 1). PP analysis showed 67.9% (57/84) of patients in group B had achieved viral suppression (< 50 copies/mL) at 12 weeks in comparison to 48.1 % (37/77) of that in group A (p< 0.01). The mean viral load levels decreased sharply in the drug B group from 4.70 ± 0.72 to 1.62 ± 0.47 log copies/ml over 12 weeks, compared to group A (p< 0.01, figure 1). However, in the two groups, CD4 counts had a similar change trend over 24 weeks and the proportion of CD4 cell counts over 200 cells/μl remained identical (figure 2). ITT analysis further demonstrated the results above.

Conclusion

Compared to TDF/3TC/EFV, BIC/FTC/ TAF as the initial choice for late presenters had better performance to achieve rapid viral suppression, especially in the first three months therapy, but showed no superiority in immune deficiency improvement.

Disclosures

All Authors: No reported disclosures
379. Research nurses in Europe: education paths and key tasks, results from VACCELERATE
Authors: Salmanton-Garcia Jon , Stewart Fiona A , Wipfler Pauline , Hofstraat Sanne H I , Bruijning-Verhagen Patricia , Cornely Oliver A
Published: November 2023

Background

From January 2023, VACCELERATE offers a specific course to become “Research Nurse”. The term “Research Nurse” makes reference to nurses actively participating in the conduct of clinical trials and epidemiological studies. Despite being key to clinical research environment, the requirements of becoming a research nurse, or which tasks are assigned, might vary between countries. We aimed to depict the current situation in Europe-

Methods

Relevant bodies in charge of nursing education in general, and Research Nurses in particular, were contacted, following advice of the VACCELERATE National Coordinators and the VACCELERATE Site Network. Participants were asked to complete an online survey on Research Nurse.

Results

Responses from 38 countries were collected. Before becoming a Research Nurse, a nursing degree was necessary in 33 (87%) countries, for which training may take 3-5 years (Figure 1). A Good Clinical Practice (GCP) course was necessary to become a Research Nurse in 24 (63%) out of 38 countries. Overall, courses relevant for compliance with Research Nurse tasks are provided by different bodies, such as: online institutions (n=18, 47%), organisations external to the respective clinical trial unit (n=16, 42%), or on site at hospitals or universities (n=14, 37%, each). Eighteen (47%) countries reported the existence of dedicated Research Nurse courses in their boundaries, but 29 (76%) considered them necessary. Administration of investigational medicinal products (country n=33, 87%) was the most commonly assigned task, both in phase I-IV clinical trials and registry trials/observational studies. Other relevant tasks were processing of blood samples (n=32, 84%), patient training for new medicines/procedures (n=30, 79%), and shipment of clinical samples (n=29, 76%). Obtaining patient informed consent (n=18, 47%) or prescription of investigational medicinal products (n=6, 16%) was a task in only a few countries.education in their country.

Conclusion

Despite the baseline educational background varying widely between countries within Europe, the tasks assigned to Research Nurses

are generally similar, which may consist of study administrative tasks, sample processing and patient training.

Disclosures

Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds
390. Corticosteroid Treatment in Severe Patients with SARS-CoV-2 and Chronic HBV Co-infection: A Retrospective Multicenter Study
Authors: Biju Sanju , Paulson Shon , Raju Jomel
Published: November 2023

Background

The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids with these patients.

Methods

This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2021, to December 1, 2022, in three centers in India, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-CoV-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of the following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroid effects was minimized using a multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on the propensity score.

Results

The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors.

Conclusion

In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with an increased risk of 28-day and in-hospital mortality.

Disclosures

All Authors: No reported disclosures
397. The Three COVID-19 Prognostic Tools (CALL, 4Cs, NLR): Head-to-Head Comparison
Authors: Doumat George , Yazbeck Hady , Itani Hassan , Wazzi-Mkahal Rayyan , Badr Mario , Moussa Elie , Barakat Salim , Osman Wael , Kanafani Zeina
Published: November 2023

Background

Risk stratification of patients is crucial for treating COVID-19 infection, but studies have not compared prognostic tools like neutrophil to lymphocyte ratio (NLR), CALL score, and 4C mortality score. Our aim is to determine the most accurate prognostic score for predicting COVID-19 patient outcomes in a retrospective cohort at a tertiary care center in Lebanon.

Methods

The study included adult patients with COVID-19 infection admitted from 2020 to 2021 at the American University of Beirut Medical Center. We calculated the NLR, CALL, and 4C scores and we recorded various outcomes for each patient. The outcomes of interest were need for mechanical ventilation (MV), intensive care unit (ICU) admission, illness progression, mortality, length of hospital stay, length of ICU stay, and length of MV. We also created a combined score from variables within each score and correlated it with outcome measures.

Results

We enrolled 401 patients with confirmed COVID-19 infection. Patients were predominantly males (67%) with an average age of 67 years. The median length of hospital stay was 15 days and illness progression was recorded in 66% of patients. Around 50% of patients required ICU admission with a median stay of 14 days, and 31% required MV with a median duration of 16 days. The mortality rate was 31%. The CALL score was a significant predictor of need for ICU admission (difference of means [DOM] 0.73), MV (DOM 0.81), disease progression (DOM 0.78), and mortality (DOM 0.90), with p≤0.01 for each outcome). The 4C score was positively associated with disease progression (DOM 1.0) and mortality (DOM 1.9) (p≤0.03 for each outcome), while NLR was only predictive of disease progression (DOM 0.2; p=0.04). The combined score was able to predict mortality (DOM 1.7; p< 0.002) but none of the other outcomes.

Conclusion

The CALL score proves to be the most useful tool in predicting several patient outcomes. However, the 4C score is a better predictor of mortality. There seems to be no added benefit from using a combined score. The evaluation of more advanced scoring systems is highly recommended to optimize risk stratification.

Disclosures

All Authors: No reported disclosures
413. Living with Long COVID: A Study on Persistent Symptoms and Vaccination Outcomes Two Years After COVID-19 Infection
Authors: Kim Yoonjung , Kim Shin-Woo , Bae Sohyun , Chang Hyun-Ha
Published: November 2023

Background

Understanding the characteristics of long COVID and the effect of COVID-19 vaccinations on patients after 24 months of COVID-19 infection is crucial for effective disease management. This study aims to determine the prevalence of long COVID and its impact on lifestyle 24 months after COVID-19 infection.

Methods

This prospective cohort study included 235 adult patients diagnosed with COVID-19 between February 17, 2020, and March 24, 2020. The participants visited the study hospital four times, at 6, 12, 18, and 24 months after acute COVID-19 infection, to assess their symptoms, quality of life, and mental health. The clinical characteristics, self-reported long COVID symptoms, EuroQol 5-dimension 5-level (EQ-5D-5L) index, Korean versions of the Patient Health Questionnaire-9 (PHQ-9), Posttraumatic Stress Disorder Checklist-5 (PCL-5-K), and Generalized Anxiety Disorder-7 (GAD-7) scale scores were investigated 24 months after acute COVID-19 infection. The presence or absence of 24-month long COVID symptoms and COVID-19 vaccination, initial disease severity, and clinical characteristics over time were compared and analyzed.

Results

Out of the 235 patients, 121 (51.5%) completed the study visits, and 75 (62.0%) still experienced long COVID symptoms 24 months after acute infection. Fatigue, amnesia, difficulty concentrating, and insomnia were the most common symptoms (Figure 1). The frequency of neuropsychiatric symptoms did not differ based on vaccination status or the number of doses received. However, patients with long COVID symptoms had significantly higher scores on measures of anxiety and depression than those without long COVID symptoms. The quality of life for the participants improved over time but still affected 32.2% of respondents, particularly in the anxiety/depression dimension.

Conclusion

This study highlights that long COVID symptoms can persist up to 24 months after acute COVID-19 infection, affecting mental health and quality of life. Although COVID-19 vaccination did not seem to impact the frequency of neuropsychiatric symptoms, further research is needed to fully understand the long-term impact of COVID-19 and the efficacy of COVID-19 vaccinations on long COVID symptoms.

Disclosures

All Authors: No reported disclosures
416. Poor clinical outcomes of COVID-19 patients receiving rituximab during the Omicron era
Authors: Lee Chan Mi , Kang Chang Kyung , Jo Hyeon Jae , Choe Pyoeng Gyun , Kim Nam Joong , Park Wan Beom , Oh Myoung-don
Published: November 2023

Background

Rituximab (RTX), a widely used anti-CD20 monoclonal antibody, has been suggested as a risk factor for poor outcomes of coronavirus disease 2019 (COVID-19). However, it remains largely unknown whether COVID-19 outcomes remain worse in patients receiving RTX compared to those not being treated with RTX during the Omicron-dominant period, when patient fatality has significantly decreased compared to the Delta-dominant period. Therefore, we aimed to investigate the outcomes of COVID-19 patients receiving RTX during the Omicron-dominant period.

Methods

Among all laboratory-confirmed COVID-19 patients who were admitted to Seoul National University Hospital from February 2022 to January 2023, those who had received RTX before diagnosis of COVID-19 were included in the RTX group, while those who had the same underlying diseases but had not received RTX were included in the non-RTX group. The COVID-19-related outcomes were compared between the RTX and non-RTX groups. Multivariate logistic regression analyses were used to identify factors associated with severe to critical COVID-19 and COVID-19-related mortality.

Results

The proportion of severe to critical COVID-19 and COVID-19-related mortality were significantly higher in the RTX group than in the non-RTX group (41.9% vs. 28.3%, P = 0.030; 11.8% vs. 2.8%, P = 0.005). RTX therapy (adjusted odds ratio [aOR] 2.21, 95% confidence interval [CI] 1.21–4.04, P = 0.010) and chronic kidney disease (aOR 3.28, 95% CI 1.56–6.91, P = 0.002) were independent risk factors for severe to critical COVID-19, whereas being effectively vaccinated (aOR 0.47, 95% CI 0.25–0.85, P = 0.013) was a protective factor. In addition, only RTX therapy was independently associated with COVID-19-related mortality (aOR 4.03, 95% CI 1.17–13.86, P = 0.027).

Conclusion

RTX therapy was associated with poor clinical outcomes of COVID-19, even in the Omicron-dominant period. This suggests that RTX should be used with caution even during the Omicron-dominant period.

Disclosures

All Authors: No reported disclosures
420. Prevalence of comorbidities and COVID-19 vaccination among COVID-19 deaths
Authors: Lyons Zin , DiBiase Lauren , Sickbert-Bennett Emily , Weber David J
Published: November 2023

Background

It is crucial to note that comorbidities may significantly increase the risk of mortality among COVID-19 patients. That's why it's vital for individuals with multiple comorbidities to make getting fully vaccinated a top priority, in order to safeguard their own health and the health of those around them. This study describes prevalence of comorbidities and COVID-19 vaccination among patients who died of COVID-19.

Methods

This was a retrospective study that assessed 220 inpatients at the UNC Medical Center who died with COVID-19 per discharge diagnosis from 7/11/21-4/3/23. Data included demographics, COVID-19 vaccination status and preexisting comorbidities. Comorbidities were classified based on CDC designated risk factors for severe COVID-19 (CDC, 2023).

Results

Of 220 patients who died, 45% were > 65 years, 60% were male, and 90% of patients had comorbidities ranging from 1 to > 3. The top 6 comorbidities among all genders and ages were hypertension (48%), heart conditions (42%), diabetes (35%), chronic kidney disease (29%), immunocompromised (29%), and obesity (25%), respectively. The proportion vaccinated was 38%; among those vaccinated, doses received were 1 (11%), 2 (40%), 3 (32%), 4 (10%), and 5 (7%). Among those who died and were vaccinated, they were 1.13 times more likely to have comorbidities (97%) compared to those not vaccinated (86%) (Risk ratio (RR) 1.13, 95% CI 1.05-1.22, P=0.004) (Table).

Prevalence of comorbidities and vaccination among COVID-19 deaths

Conclusion

In this cohort study of COVID-19 deaths, the majority of patients dying with COVID-19 were White, non-Hispanic, males > 65 years with comorbidities, most often with multiple comorbidities. Hypertension, heart conditions, diabetes, chronic kidney disease, immunocompromised, and obesity emerged as the most common comorbidities. More than half of the patients had not received COVID-19 vaccination. This highlights the importance of getting fully vaccinated, especially for those with pre-existing conditions.

Disclosures

David J. Weber, MD, MPH, BD: Advisor/Consultant|Germitic: Advisor/Consultant|GSK: DSMB|PDI: Advisor/Consultant|Pfizer: Advisor/Consultant|Wellair: Advisor/Consultant
423. Development and Validation of a Predictive Model of New-Onset Deep Vein Thrombosis/Pulmonary Embolism Among Hospitalized COVID-19 Patients: A Retrospective Cohort Study
Authors: Meng Qingqing , Rodriguez-Nava Guillermo , Egoryan Goar , Kishmiryan Armen
Published: November 2023

Background

COVID-19 can increase the risk of thromboembolism events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE). This study aimed to develop a risk prediction model for new-onset DVT/PE in hospitalized COVID-19 patients based on baseline characteristics, major complaints, and lab values.

Methods

Retrospective data from 671 hospitalized COVID-19 patients were collected between March and October 2020. After excluding missing values, 241 cases were included in the final analysis (Table 1). Lasso regression was used to select related variables, and a prediction model was built using logistic regression (Figure 1). A nomogram was established based on multivariate analysis, and the model was validated using the bootstrap method.

Results

Among the 241 hospitalized patients with COVID-19 infection, 18 (7.5%) developed new-onset DVT/PE during hospitalization. The final prediction model included the history of diabetes mellitus, chills, sore throat, anorexia, hemoglobin, and D-dimer levels on admission. A predictive nomogram model for new-onset DVT/PE based on these variables was built (Figure 2). Our prediction model showed good predictive performance with an area under the curve (AUC) of 0.89 and a bootstrap-corrected AUC of 0.82 (95% CI: 0.767-0.873) (Figure 3). The calibration plots demonstrated good agreement between the estimated probability and the actual observation (Figure 4A). Decision curve analysis shows the nomogram is clinically useful (Figure 4B).

Conclusion

The developed model for new-onset DVT/PE in hospitalized COVID-19 patients based on baseline characteristics, major complaints, and lab values had good discrimination and calibration. It may help identify high-risk patients who require close monitoring and prophylactic anticoagulation. Future studies are needed to validate the model in different populations and settings.

Disclosures

All Authors: No reported disclosures
424. High Prevalence of Neuropsychiatric Symptoms and Pre-COVID-19 Mental Health Disorders in Patients with Post-Acute COVID
Authors: Mokraoui Nassim , Brenner Sara , Westlake Amanda , Rastegar Vida , Skiest Daniel
Published: November 2023

Background

Individuals with post-acute COVID syndrome (PAC), also known as long-COVID, have new or continuing symptoms lasting more than 1 month from COVID-19 infection. Patients may present with neuropsychiatric (NP) and non-NP symptoms. Whether prior mental health disorders correlate with NP symptoms is unknown. The study aims were to describe the demographics, clinical factors, comorbid conditions, and presenting symptoms of PAC.

Methods

We included patients evaluated at Baystate Health PAC clinic from January 2021-April 2022, with prior COVID-19 infection and new or persistent symptoms of at least 6 weeks. We defined the primary presenting symptoms as NP (cognitive dysfunction (brain fog), anxiety, or depression) or non-NP (dyspnea, fatigue, dizziness, palpitations). The clinician’s diagnostic impression was recorded and characterized as NP or non-NP.

Demographics

Results

We randomly selected 150 of 250 clinic patients for chart review. Most were women, 117 (78%); mean age was 52. Most 106 (71%) had mild acute COVID illness; 36 (24%) were hospitalized. 49% (n=73) had a pre-existing mental health disorder: mood disorder (depression/bipolar) 26 (17%), anxiety 18 (12%), both anxiety and mood disorder 27 (18%). The most common presenting symptoms in order of frequency were fatigue, dyspnea, brain fog, anxiety, depression, and palpitations. 106 (71%) had at least 1 NP presenting symptom or combination of NP symptoms; cognitive dysfunction with anxiety in 23 (15%), and cognitive dysfunction with anxiety and mood disorder in 13 (9%). The clinician's final diagnostic impression was fatigue (47%), cognitive dysfunction (36%), anxiety (29%) depression (33%) and PTSD (3%). A NP diagnosis was made in 81 (54%).

Primary Symptoms

Primary Diagnosis

Conclusion

The majority of PAC clinic patients were female and had mild COVID illness. We noted a high prevalence of pre-existing mental health disorders. More than two-thirds presented with one or more NP symptom. Further studies should explore the association of pre-COVID mental health disorders with PAC.

Disclosures

All Authors: No reported disclosures
425. Characterization and predictive risk scoring of long COVID in a South Indian cohort after breakthrough COVID infection; a prospective single centre study
Authors: Moni Merlin , Nair Pranav , Nair Chithira , Kulirankal Kiran , Corley Elizabeth , Edathadathil Fabia , Gutajhr Georg , Sathyapalan Dipu T
Published: November 2023

Background

The majority of existing literature on long COVID has been focused on hospitalised patients. However, in the real-world setting of the post-vaccination era where breakthrough infections are the norm, it becomes a priority to assess the clinical profile of long COVID symptoms among such individuals. Through our study, we aim to describe the incidence, characterise and stratify the risk of developing long COVID breakthrough infections.

Methods

This prospective observational study included adult patients with breakthrough COVID-19 infections diagnosed at a tertiary hospital in India. Post-COVID symptoms at weeks 2, 6 and 12 after testing negative were extracted using a questionnaire after which multi-variate analysis was done.

Results

Out of 414 patients analysed, 164 reported post-COVID symptoms beyond 6 weeks of the infection. Univariate analysis showed that the presence of long COVID was found to be significantly higher among patients above 65 years of age at 31.3% in comparison to the long COVID presence at 29.4% among those below age 65 (p < 0.001). Systemic hypertension was also significantly associated with the presence of long COVID (72.3%), along with bronchial asthma (68.8%) with a p-value of < 0.0001 in both instances. Backwards selection was used leading to a reduced model consisting of age OR 1.053, 95% CI 0.097–1.07), p < 0.001), hypertension (OR 2.59, 95% CI 1.46–4.59, p = 0.001) and bronchial asthma (OR 3.7176, 95% CI 1.24–11.12, p = 0.018) to be significant predictors of long COVID incidence. These were used to develop a propensity score (C statistics – 80.9%).

1A: Long COVID symptomatic profile at weeks 2, 6 and 12 weeks 1B: Organ system wise distribution of long COVID symptoms at 2, 6 and 12 weeks

Conclusion

A significant presence of long COVID at 12 weeks among non-hospitalised breakthrough infections calls for a series of review check-ups for the early detection of long-term complications. The proposed predictive risk scoring based on significant risk factors may assist clinicians in identifying patients at risk of developing long COVID, leading to appropriate, individualised management.

Table 4

Figure 3A & 3B

3A: Logistic regression model for predicting long COVID incidence 3B: Clinical prediction nomogram to depict risk of long COVID incidence

Figure 4A & 4B

4A: Association of propensity risk score for Long COVID incidence with symptom burden 4B: Association of propensity risk score for Long COVID incidence with functional status

Disclosures

All Authors: No reported disclosures
428. Risk Stratification and Clinical Outcomes in a Mixed Vaccination Cohort of COVID-19 Patients Admitted in a Tertiary Hospital Using ISARIC 4C Scores
Authors: Pascual May Anne S , Reyes John Robinson L
Published: November 2023

Background

The risk of clinical deterioration and death with the use of prognostic tools remain necessary for strategic planning among COVID-19 patients. The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) developed and validated Coronavirus Clinical Characterization Consortium (4C) scores to predict clinical deterioration and mortality. ISARIC 4C scores uses readily available clinical parameters. With the increasing uptake of COVID-19 vaccine, there is a need to evaluate these tools. The study examined a cohort of fully vaccinated (FV), partially vaccinated (PV) and unvaccinated (UV) COVID-19 patients and determined their clinical outcomes and stratified risks using ISARIC 4C scores.

Methods

We reviewed medical records of confirmed COVID-19 patients admitted to a single tertiary hospital between May 2021 and April 2022. Vaccination status were classified as FV, PV and UV. The primary outcome was in-hospital mortality. Baseline data were collected and predictors recorded upon admission were used to calculate the 4C scores. Multiple logistic regression analysis was used to determine the association of vaccination status and 4C Deterioration and Mortality scores with in-hospital mortality. STATA 14 was used for data analysis and p< 0.05 was considered statistically significant.

Results

A total of 301 confirmed COVID-19 patients were included and 46.5% were fully vaccinated. FV patients had significantly lower CRP (p< 0.0001), had higher mean oxygen saturation (p< 0.0001), had lower mean mortality score (p=0.004), had lower mean % risk for deterioration (p< 0.0001) and had significantly lower 30-day mortality (< 0.0001) compared to those UV and PV. Patient who died had significantly higher mean age (p=0.001), lower mean lymphocyte ratio (p=0.0004), had significantly higher mean deterioration and mortality score (p< 0.0001). Being fully vaccinated was associated with lower risk for mortality (OR=0.4, 95%CI=0.2 to 0.7).

Conclusion

Fully vaccinated patients were at lower risk for deterioration and mortality. High ISARIC 4C scores were also significantly associated with higher risk for mortality. Risk stratification tools should be utilized in COVID-19 management as they provide a helpful means to identify patients at risk for worse outcomes.

Disclosures

All Authors: No reported disclosures
446. Post-Acute Sequelae of COVID-19 in a Rural Wisconsin Community Prospective Cohort
Authors: Sundaram Maria , Alonge Oluwakemi , Petrie Joshua , Feldstein Leora R , Rolfes Melissa A , Kawaoka Yoshihiro , Neumann Gabriele , Belongia Edward , McLean Huong
Published: November 2023

Background

Some individuals experience post-acute sequelae of SARS-CoV-2 (PASC), a variety of persistent symptoms related to different organ systems after a SARS-CoV-2 infection. There are limited data on the prevalence of PASC after SARS-CoV-2 Omicron variant infection. We assessed the relative risk of persistent symptoms consistent with PASC, during a period of SARS-CoV-2 Omicron circulation.

Methods

A longitudinal cohort in rural Wisconsin was followed from November 2020 – July 2022 to assess incidence of SARS-CoV-2 infection. In March – April 2023, participants completed a survey about ongoing symptoms lasting ≥ 4 consecutive weeks and beginning on or after January 2022 (Omicron period). Poisson regression models were used to assess the relative risk of persistent symptoms overall and by symptom category among those with RT-PCR-confirmed or self-reported SARS-CoV-2 infection since January 1, 2022 (Omicron infection) vs. no history of SARS-CoV-2 infection (by self-report or RT-PCR detection), controlling for participant age group (17-49 vs. ≥50 years), having ≥2 COVID-19 vaccine doses before 2022 (yes/no) and chronic health conditions (yes/no).

Results

Of 573 respondents aged ≥17 years (66% response rate), 63% were female, 60% were ≥50 years old, and 51% had a chronic health condition. The presence of ≥2 persistent symptoms was 27% among Omicron-infected individuals and 24% among never-infected individuals (28% for those with SARS-CoV-2 infection prior to 2022). The risk of having ≥2 persistent symptoms was similar for Omicron-infected vs. never-infected individuals (adjusted relative risk [aRR]: 1.1; 95% CI: 0.9, 1.4). In models investigating symptom categories, aRRs for cardiac, pulmonary, neurologic, and menstrual symptoms were elevated (but not statistically significant) for Omicron-infected vs. never-infected individuals (Figure 1).Figure 1.Relative risk of PASC-related symptoms by category among individuals with Omicron infection, compared to individuals with no history of SARS-CoV-2 infection.

Conclusion

Preliminary data from this cohort show presence of persistent symptoms with and without a history of SARS-CoV-2 infection. We observed elevated though non-significant aRRs for cardiac, pulmonary, and neurologic symptoms for Omicron-infected individuals, similar to other findings in the literature. Although data are sparse, elevated aRRs for auditory and menstrual outcomes may warrant further analysis.

Disclosures

Maria Sundaram, PhD, MSPH, GlaxoSmithKline: Grant/Research Support Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support Gabriele Neumann, Ph.D., FluGen: US-20110150925-A1, US-20100021499-A1, US 8,163,523 B2|FluGen: Ownership Interest|FluGen: Stocks/Bonds Edward Belongia, MD, Seqirus: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support