bluuebunny/crossref_metadata_2025 huggingface dataset:
1019. The Future is Embedded in the Present - Characterizing Pharmacist Interventions in an Infectious Diseases Clinic
Authors: Depcinski Shawn , Bhargava Ashish
Published: December 2022

Background

Incorporating clinical pharmacists into the outpatient care setting can improve patient outcomes; however, the focus has mostly been on primary care. In 2021, Ascension Specialty Pharmacy embedded clinical pharmacists into clinics prescribing specialty medications to increase prescription capture and improve patient care. The clinical pharmacist incorporated into the Ascension St. John Infectious Diseases clinic provides patient outreach, care coordination, financial and prior authorization assistance, medication reconciliation and counseling, and clinical interventions. This study characterizes the pharmacist interventions provided during a six month timeframe.

Methods

As of September 2021, the clinical pharmacist’s interventions were consistently captured in a documentation system. Each patient encounter that resulted in one or more interventions were entered as one documentation event, which captures type of problem, recommendation category, intervention acceptance, and estimated time spent. If more than one problem within the same type occurred on a patient, it could only be recorded as one problem. A report was pulled over a six month period of September 2021 through February 2022.

Results

During the timeframe reported, infectious disease specialty prescriptions filled at Ascension Specialty Pharmacy had nearly doubled from before embedding the pharmacist (monthly average, 115 vs. 66). During the study period, 316 patient encounters resulted in clinical pharmacist interventions, which included 594 problem types. The frequency of problem types included under-treatment (32%), medication monitoring needed (28%), suboptimal drug (18%), sub-optimal dosing/duration/frequency/administration (12.52%), nonadherence (5.92%), and adverse drug event (4.74%). Pharmacist interventions were accepted 90% by physicians and 81% by patients. The pharmacist time spent on interventions was estimated at 203 hours during the study period.

Conclusion

Despite limitations in how interventions are documented and reported, this study demonstrates the significant impact a clinical pharmacist embedded into an infectious diseases clinic can have on optimizing patient care.

Disclosures

Shawn Depcinski, PharmD, bioMérieux: Honoraria.
1023. Thrice is Nice: Thrice Weekly Ertapenem Versus Daily Ertapenem in Patients on Hemodialysis
Authors: Mulugeta Surafel , Procopio Vince , Mannino Ii Andrew C , Aref Nada , Kwiatkowski Shaina
Published: December 2022

Background

Outpatient parenteral antimicrobial therapy (OPAT) has challenges: venous access complications, cost, and non-adherence. Venous line preservation is an added concern for patients on hemodialysis (HD). While ertapenem is dosed 500 mg daily post-HD, there is limited data on dosing it as 1 gm thrice weekly. This study compares disposition and outcome in patients treated with these two regimens.

Methods

IRB approved, retrospective cohort study. Inclusion: adult patients on intermittent HD, admitted 6/1/20 to 7/31/21, and discharged with ertapenem either with daily (daily group) or thrice weekly (TIW group) dosing. Data were reported using descriptive statistics and bivariate analysis. Primary endpoints: discharge delay after medical stability. Secondary endpoints: efficacy (readmissions, alterations in antibiotics, and mortality) and safety (line or drug – related adverse events including line infection and seizure).

Results

33 patients included: 10 daily and 23 TIW. Baseline characteristics were similar. Median (IQR) age: 57 (48-64) daily and 63 (47-70) TIW, P=0.552. Both groups had a high median Charlson index (IQR): 5 (4-5) daily and 4 (2-5) TIW, P=0.287. Primary reason for ertapenem use was infection from extended-spectrum beta lactamase producing organism: 60% daily and 52% TIW. The TIW group had significantly fewer lines placed (80% daily vs. 22% TIW, p=0.05). Median (IQR) length of stay in days was similar: 7 (6–15) daily and 8 (6-8) TIW, P=0.773. Discharge delays were similar (10% daily vs 9% TIW, P=1.0). Most patients were discharged home (60%). More patients received ertapenem at the dialysis center or infusion clinic in the TIW group (78% TIW vs 30% daily, P=0.016). There was no difference in safety and efficacy endpoints including readmission, mortality, alternation in antibiotics, and line infection.

Conclusion

In this study’s cohort, ertapenem thrice weekly dosing led to a decrease in line placement without compromising efficacy and safety.

Disclosures

All Authors: No reported disclosures.
1029. Clinical Characteristics and Outcomes of Neuroinvasive West Nile Virus Infection in Immunocompromised and Immunocompetent Individuals
Authors: Mbonde Amir , David Gritsch , Harahsheh Ehab , Kasule Sabirah N , Vikram Holenarasipur R , Hasan Shemonti , Butterfield Richard , Grill Marie
Published: December 2022

Background

Despite the increasing incidence of neuroinvasive West Nile virus (NiWNV) infection in the US, the spectrum of disease characteristics and neuroimaging findings in immunosuppressed (IS) individuals are not adequately described. We aimed to compare the clinical characteristics and outcomes of NiWNV infection in IS and immunocompetent (IC) patients.

Methods

We extracted relevant data from all NiWNV patients hospitalized 7/2003-10/2021 at Mayo Clinic hospitals. Cohort was inclusive of patients from the recent historic WNV outbreak in Arizona in 2021. Chi-Square or Kruskal-Wallis and logistic regression were used to compare relevant variables and determine predictors of mortality respectively.

Results

We included 115 patients (72 IC and 43 IS), mean age 63.5 years; neurologic syndromes included meningoencephalitis (85.2%), encephalomyelitis (8.7%) and myeloradiculitis (6.1%). Presenting symptoms were malaise (72%), fever (66%), altered mentation (64%), gastrointestinal (47%) and myalgia (35.7%). MRI brain was abnormal in 62.8% (49/78), demonstrating T2/FLAIR hyperintensities in 47.4% (brainstem, thalamus, temporal lobes), leptomeningeal enhancement (16.7%) and diffusion restriction (20.5%). Altered mental status (76.7% vs 56.9%), myalgia (44.4% vs. 20.9%), myoclonus (18.6% vs. 4.2%) and thalamic MRI T2 FLAIR abnormalities (11.4% vs 0%) were more common in IS patients. Higher CSF WBC counts were observed in IC vs IS patients (P< 0.05). Immunosuppressed patients were more likely to be treated with intravenous immunoglobulin (44.2% vs 8.3% p=< 0.001) and/or interferon therapy (32.6% vs 6.9%, p=0.0003) and had increased odds of 90-day mortality on multivariable analysis (Adjusted Odds Ratio, AOR 2.22; 95% CI 1.065-4.627, p=0.0334). In the IS subgroup, ICU admission, mechanical ventilation, and Glasgow coma scale of < 8 were associated with reduced overall survival/increased 90-day mortality (p< 0.005).

Conclusion

Individuals presenting in summer/fall months with the aforementioned symptoms and/or MRI abnormalities should be evaluated for NiWNV infection. Compared to the immunocompetent, immunosuppressed patients with NiWNV are at a significantly greater mortality risk. Novel and effective antiviral therapies aimed at improving outcomes are warranted.

Disclosures

All Authors: No reported disclosures.
1038. Assessment of risk factors for coronavirus disease 2019 in healthcare workers: a nested case-control study, Bishkek, Kyrgyzstan, June 2020-May 2021
Authors: Alymkulova Venera , Nabirova Dilyara , Kemelbek kyzy Nasyat , Otorbaeva Dinara , Zhumalieva Chynar , Abamuslimova Nazgul
Published: December 2022

Background

Despite infection control and mitigation measures against coronavirus disease (COVID-19) in Kyrgyzstan hospitals, 3173 healthcare workers (HCW) had been diagnosed with COVID-19 by September 2020 (22 COVID-19 cases/100 HCW). We aimed to identify risks for COVID-19 among HCW exposed to COVID-19 patients in Bishkek.

Methods

We conducted a case-control study in six hospitals with high COVID-19 incidence using incidence-density sampling. Cases were HCW with positive SARS-CoV-2 PCR and negative SARS-CoV-2 IgG results June 2020-May 2021 exposed to COVID-19 patients < 14 days prior to PCR positive test. Controls were randomly selected HCW working with COVID-19 patients at the same time with negative SARS-CoV-2 PCR and IgG results. HCW with COVID-19 contacts outside of the work setting were excluded. We used logistic regression to identify factors associated with COVID-19.

Results

We included 132 cases and 406 controls; 479 (89%) were women, and 256 (48%) were ages < 40 years. HCW wore different types of masks; among these medical respirators (FFP3) were used by 49% of cases vs 28% of controls. Comorbidities were reported in 34% of cases vs 14% of controls; 90% of cases vs 91% of controls stayed in shift-dormitories. Odds of COVID-19 were greater for HCW who used FFP3 vs other types of respirators including N95 (adjusted odds ratio=2.9, 95% confidence interval [CI]: 1.1–3.9), shared a shiftwork dormitory with another HCW diagnosed with COVID-19 vs not (2.9, CI: 1.5–5.5), and had a comorbidity vs not (2.3, CI:1.4–5.0).

Conclusion

HCW can become infected from exposures in a variety of settings. Our findings showed an association of COVID-19 with shared dormitory, comorbidity and FFP3 use. Results are not causal, but they point to the need for increased infection control and mitigation in communal spaces, including dormitories. Additionally, hospitals should ensure quality of respirators and correct training on respirator use.

Disclosures

All Authors: No reported disclosures.
1043. Gastrointestinal manifestations of COVID-19 and their association with disease severity and death in the Dominican Republic
Authors: Roque Yori A , Luna David De , Mena Lora Alfredo J , Santana Ysalda E , Rodriguez Alicia , Ramos Johan , Suarez Mariel
Published: December 2022

Background

The COVID-19 pandemic has strained healthcare systems worldwide. The disease spectrum of COVID-19 is wide, ranging from asymptomatic to respiratory distress and critical illness. A wide range of associated symptoms have been described, including gastrointestinal manifestations. Defining clinical characteristics that can help identify and triage cases towards COVID-19 treatment pathways early in low-and-middle income countries is of priority.

Methods

Single center retrospective review of cases admitted to a tertiary center with COVID-19 and gastrointestinal symptoms between March 2020 and November 2021. Inclusion criteria was defined as molecular diagnosis of SARS-CoV-2 with symptomatic gastrointestinal disease. Demographic and clinical characteristics were tabulated, and statistics of association and mortality were performed.

Results

A total of 95 cases admitted with SARS-COV2 pneumonia met the inclusion criteria. Cases were predominantly male (65.3%). Age distribution was 48.4% >61 years, followed by 51-60 (17.9%), 31-40 (15.8%) and 41-50 years (13.7%). The gastrointestinal findings associated with COVID-19 were transaminitis (48.4%), Nausea and diarrhea (29.5%), anorexia (28.4%) and abdominal pain (13.7%). Patients with abdominal pain had 46% with respiratory decompensation and 23% critical illness (Figure 1) compared to 39% and 17.9% in patients with diarrhea. Transaminitis was associated with highest association with progression to critical illness (30%) and death (55%).

Respiratory decompensation, critical illness and death by gastrointestinal findings

Conclusion

Gastrointestinal symptoms in COVID-19 have a wide range of clinical presentation and can be associated with severity of illness and decompensation. Transaminitis had the highest association with severe disease and death. These associations, if confirmed in larger studies, can help guide triage and prognostication in resource limited settings. Further studies are needed to validate these findings.

Disclosures

All Authors: No reported disclosures.
1059. The Experiences of Healthcare Workers during the Second Wave of COVID-19 Crisis in the South Indian State of Kerala
Authors: Issac Aleena , Kochuparambil Jose J
Published: December 2022

Background

The COVID-19 pandemic has presented an unprecedented crisis and challenge for healthcare professionals globally. This study aims to explore the challenges faced by healthcare professionals during the second wave of COVID-19 in the south Indian state of Kerala.

Methods

An online cross-sectional survey was designed and disseminated through social media and professional organizations to collect the relevant information from the healthcare workers. The questionnaire composed of demographics, and of questions about the employment, work role, and access to personal protective equipment.

Results

Of the 423 responses received, 268 (63.3%) were nurses, followed by pharmacists (7.4%), doctors (14.6%), and allied healthcare professionals (4.4%). Nearly half i.e., 198 (46.8%) of the total responders, expressed concern about work-related risks to themselves and their families. The primary concerns expressed by the participants include higher workload, psychological distress, shortage of quality personal protective equipment (PPE), lack of incentives, and social stigmatization. Just over a third of respondents (35%) perceived that care provided in their workplace was significantly worse than before the pandemic.

Conclusion

The study offers lessons for hospitals in middle-income and low-income countries to ensure a safe working environment for front-line healthcare workers in their fight against COVID-19. This implies the need to support with adequate safety kits, protocols, and support for both physical and mental health of the healthcare professionals.

Disclosures

All Authors: No reported disclosures.
1061. Evaluation of Measures for the Assessment of Covid-19 Signs and Symptoms in Children and Adolescents
Authors: Romano Carla , Mayorga Margaret , Ruiz-Guiñazu Javier , Trudel Géralyn C , Fehnel Sheri , McQuarrie Kelly , Chan Eric K H , Katz Eva G
Published: December 2022

Background

The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure developed to assess the presence and severity of COVID-19 signs and symptoms in adults. To further facilitate the evaluation of new vaccines and treatments in development, similar tools are needed for use within pediatric populations. The objectives of this study were to support adolescent self-completion and create an adaptation of the measure for caregiver assessment of signs and symptoms in children aged < 12 years (henceforth, the Pediatric SIC [PedSIC]).

Methods

After developing draft versions of the PedSIC and reference materials with definitions to facilitate accurate completion of both measures, iterative rounds of cognitive debriefing interviews were conducted from November 2020 through January 2021 to evaluate understanding of the SIC (in adolescents aged 12-17), and inform refinement of the PedSIC for caregivers of children aged < 12. Recruitment quotas were employed to support sample diversity.

Results

Nine adolescents (mean [SD, range] age, 14 [1.76, 12-17] years, 56% female, 78% white; round 1, n=6; round 2, n=3) and 17 caregivers (mean [SD, range] age, 34 [6.28, 26-41] years, 59% female, 65% white; round 1, n=9; round 2, n=8) completed interviews. All adolescents understood and completed the adult version of the SIC without instrument modification. Ease and accuracy of self-completion was improved through the use of reference materials. Caregiver feedback resulted in modification of the PedSIC to include two sections: observable signs (ages < 12), and symptoms assessed with input from children (ages ≥ 5-< 12). Reference materials provided standardization of item intent.

Conclusion

Results support using the SIC, PedSIC, and their associated reference materials to assess the presence and severity of COVID-19 signs/symptoms in adolescents and children aged < 12 years, respectively, who participate in vaccine and treatment clinical trials. Supported by Janssen Vaccines & Prevention B.V.

Disclosures

Carla Romano, MS, Janssen Pharmaceuticals: Grant/Research Support Margaret Mayorga, MS , MPH, Janssen Pharmaceuticals: Grant/Research Support Javier Ruiz-Guiñazu, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Géralyn C. Trudel, PhD, Janssen Pharmaceuticals: Stocks/Bonds Sheri Fehnel, PhD, Janssen Pharmaceuticals: Grant/Research Support Kelly McQuarrie, BSN, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Eric K. H. Chan, PhD, Janssen Global Services, LLC: Employee|Janssen Pharmaceuticals: Stocks/Bonds Eva G. Katz, PhD, MPH, RD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds.
1067. Predicting next 7-day Discharges of Hospitalized COVID-19 Patients Using Ensemble Learning
Authors: Ye Xiangyang , Zhang Mingyuan , Samore Matthew H , Shen Jincheng , Bohman Julia , zhang Yue , Humpherys Jeffrey
Published: December 2022

Background

COVID-19 pandemic, especially during resurgences of cases in hard-hit areas, led to significant shortage of hospital beds. Such shortages may be alleviated through timely and effective forecasting of hospital discharges. The objective of this study is to predict next 7-day discharges of hospitalized COVID-19 patients using daily-based electronic health records (EHR) data.

Methods

Using EHR data of hospitalized COVID-19 patients from 03/2020-08/2021, we employed ensemble learning to predict next 7-day discharges of individual patients. We used both baseline and daily inpatient features for model training, validation, and test. Baseline features include demographic and clinical characteristics, and comorbidities. The daily inpatient features were vital signs, laboratory tests, medications administered, acute physiological scores, use of ventilator, and use of intensive care unit.

1832 hospitalized patients were identified (12,397 hospital days). Samples were randomly split at patient level (7:2:1) into training set (N=1,283 patients with 8,704 hospital days), validation set (N=366 patients with 2,524 days), and test/holdout set (patient N=183, and 1,169 days). Prediction models were trained on the training set and the validation set. We conducted the model training separately on the samples of admission day and the samples of days after admission day.

The predictions were based on the ensemble learning from decision tree, XGBoost, logistic regression, and multilayer perceptron, long short-term memory (LSTM), bi-directional LSTM, and convolutional neural network.

The combination of ensemble learning on the test/holdout set was used for final next 7-day predictions based on ‘hard’ voting (by majority). Where there was a tie, we used ‘soft’ voting (sum of probabilities) to break the tie. Figure 1.Data Processing PipelineFigure 2.Ensemble Model Architecture

Results

The overall average hospital length of stay was 8.7 (SD=10.5) days. The ensemble learning accuracies for admission-day samples and after-admission-day samples were 0.781 and 0.793, and the F1-scores for were 0.761 and 0.789, respectively.

Conclusion

EHR data of hospitalized COVID-19 patients can be used to predict next 7-day hospital discharges. Additional inpatient features and more advanced machine learning techniques are needed for prediction accuracy improvement.

Disclosures

All Authors: No reported disclosures.
1075. The MET Project: Distinguishing Multisystem Inflammatory Syndrome in Children from Typhus Using Artificial Intelligence
Authors: Chun Angela , Bautista Abraham , Weatherly Chad , Osuna Isabella , Nasto Kristiana , Munoz Flor M , Schutze Gordon , Devaraj Sridevi , Muscal Eyal , Tejtel Kristen Sexson , Vogel Tiphanie , Kakadiaris Ioannis
Published: December 2022

Background

Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection shares features with other inflammatory states, notably Kawasaki Disease. The rickettsial infection murine typhus is also in the differential for MIS-C in endemic areas. As the therapeutic approaches differ, it is essential to distinguish these disorders soon after presentation, well before confirmatory serologic testing results. Our objective was to develop an algorithm to accurately predict MIS-C versus typhus.

Methods

Retrospective review extracted demographic, clinical, and laboratory features available within 6 hours of presentation for 133 MIS-C and 87 typhus patients. 33 features were broken into 44 inputs and passed through an attention module to compute importance. Inputs were then entered into machine learning algorithms as MIS-C or typhus. Patients were divided into training and test cohorts respecting proportions in the dataset. An equation was built to calculate the “MET” (MIS-C versus endemic typhus) score.

Results

MIS-C patients were younger (8.4 v 11.2 years, p< 0.0001) and the majority (71%) presented on day 4-6 of fever; most typhus patients (84%) presented with ≥6 days (mean 4.9 v 7.3 days, p< 0.0001). Typhus patients were more likely to have rash (86% v 51%, p< 0.0001) and MIS-C patients red eyes (71% v 36%, p< 0.0001), other features were similar. MIS-C patients had higher C-reactive protein levels (17.7 v 9.8 mg/dL), procalcitonin (14.0 v 0.48 ng/mL), fibrinogen (558 v 394 mg/dL) and neutrophil-to-lymphocyte ratio (12 v 3.5), all p< 0.0001, other parameters were similar. MIS-C patients were also more likely to have elevated troponin (0.48 v 0.01 ng/mL, p< 0.0001) and require intensive care (66% v 6%, p< 0.0001). A long short term memory network outperformed 6 other models (99% accuracy using all 33 elements). The MET score predicted MIS-C versus typhus with 90% accuracy using only 10 features (sensitivity 90%, specificity 90%).

Conclusion

The clinical and laboratory similarities between typhus and MIS-C present challenges, but they can be reliably distinguished using artificial intelligence with as little as 10 features. Our ongoing interprofessional collaboration aims to make the MET score readily available to clinicians for use in patient encounters.

Disclosures

Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB Tiphanie Vogel, MD, PhD, Moderna: Advisor/Consultant|Novartis: Advisor/Consultant|Pfizer: Advisor/Consultant.
1081. Clinical Characteristics and Predictive Factors for the Development of Hypoxemia in SARS-CoV-2 Infected Women during Pregnancy
Authors: Kim Young Keun , Kim Eui Hyeok , Choi Hee Kyoung
Published: December 2022

Background

There is limited information describing the clinical characteristics and prognosis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy. The clinical features and the predictive factors for development of hypoxemia were investigated in SARS-Cov-2 infected women during pregnancy.

Methods

From August 2020 to February 2022, 410 pregnant women were infected with SARS-CoV-2 who admitted to two hospitals, the National Health Insurance Service Ilsan Hospital in Goyang or the Wonju Severance Christian Hospital in Wonju, Korea. The clinical characteristics and prognosis were compared between pregnant women who required oxygen or not during hospitalization.

Results

The mean age of the patients was 33.3 years. The hospitalized pregnant women were categorized into two groups such as no oxygen group and oxygen group. Of 410 patients, 100 (24.4%) required oxygen therapy (81 low-flow, 15 high-flow oxygen and 4 mechanical ventilation including 2 extracorporeal membrane oxygenation). In oxygen group, the symptoms such as fever [163 (52.6%) vs 81 (81.0%), p< 0.001] and cough [172 (56.4%) vs 73 (73.0%), p=0.003] were frequently observed. In oxygen group, the frequency of whom were not vaccinated was more [264 (85.2%) vs 98 (98.0%), p=0.003], however, that of the SARS-CoV-2 omicron variant infected patients was lower [98 (31.6%) vs 18 (18.0%), p=0.009]. The risk for the development of hypoxemic respiratory difficulty was increased if the SARS-CoV-2 infection during third trimester (OR 5.083, 95% CI 1.095-23.593, p=0.038) and elevated C-reactive protein (≥1.0 mg/dL) at admission (OR 5.878, 95% CI 3.099-11.146, p< 0.001) in the SARS-CoV-2 infected pregnant women. However, the risk was decreased with vaccination (OR 0.186, 95% CI 0.041-0.838, p=0.028) and omicron variant infection (OR 0.498, 95% CI 0.258-0.961, p=0.038).

Conclusion

A quarter of SARS-CoV-2 infected women during pregnancy developed hypoxemic respiratory difficulty. The SARS-CoV-2 infection during third trimester and no vaccination increased the risk for the development of hypoxemic respiratory difficulty in pregnant women.

Disclosures

All Authors: No reported disclosures.
1092. Management of Transplant Graft and Role of Immunosuppression in the Outcome of Covid-19 Infection in Solid Organ Transplant Recipients
Authors: Sabunwala Suhel A , Cornelius Tuhina , Aslam Sadaf , Alrabaa Sally , Kumar Ambuj
Published: December 2022

Background

COVID-19 disease became a global health care crisis and was declared pandemic by WHO in March 2020. Little is known how the immunosuppressive medications impact the mortality rate in Solid Organ Transplant (SOT) recipients. There is also minimal data regarding the incidence of transplanted graft failure or rejection that could be attributed to the COVID-19 infection itself or its complications and management. Our study aims to investigate the management of COVID-19 infection, outcome of the infection, transplant failure and rejection rates in SOT recipients.

Methods

We conducted a retrospective cohort study of all consecutive SOT recipients who were admitted to our transplant center from March 2020 to April 2021 with COVID-19 infection. Data was collected from the electronic medical records after receiving Institutional Review Board approval. Table 1Characteristics of the Population in the two groups

Table 2 Type of Transplants in the two groups

Results

A total of 135 patients met the inclusion criteria. After the diagnosis of COVID -19 infection, 31% recipients had decrease in the dose of immunosuppressive medications (change group) and 69% had no changes in the dose (no change group). Out of the 73 Kidney Transplant recipients 33% were in the change group compared to 14% of liver, 25% of heart and 27% of lung transplant recipients. Of the total 42 recipients in the change group, 28.6% required Intensive Care Unit (ICU) level care significantly higher compared to 7.5% in the no change group (p-value < 0.005). Mechanical ventilation was required in 14.3% of the patients in the change group and 6.5% in the no change group (p-value < 0.5). Out of the total, 85.7% patients in the change group survived compared to 94.6% in the no change group (p-value < 0.1). Overall, the transplant rejection rate was higher in the change group compared to the no change group (p-value < 0.5). Table 3Comparison of the Outcomes in the two groups

Figure 1 Kaplan – Meier Curve for survival

Figure 2 Kaplan – Meier Curve with Cox Regression for survival

Conclusion

Our study showed a significantly higher ICU admission rate and mortality in SOT recipients who had their immune suppression reduced at the time of COVID-19 diagnosis. The same group also had a higher risk of rejection of transplanted graft. More studies with larger sample size needs to be done to further understand the management of immunosuppressive drugs in the SOT recipients with COIVD-19 infection.

Disclosures

All Authors: No reported disclosures.
1095. Retrospective Review of SARS-CoV-2 Infection in Immunocompromised Children at a Single Pediatric Institution
Authors: Khan Aslam , Mathew Roshni , Rosenthal Ayelet
Published: December 2022

Background

Immunocompromised individuals are considered higher risk for severe COVID-19 disease. Much of this data was collected from adults with limited pediatric reporting, although a recent study showed no worse outcome in immunocompromised children. In this study, we characterize our experience of immunocompromised children who were hospitalized with acute SARS-CoV-2 infection and aimed to identify a sub-group of patients who had worse outcomes.

Methods

We reviewed charts of all immunocompromised children hospitalized with SARS-CoV-2 RT-PCR positive results at our hospital from March 2020-April 2022. Disease severity was characterized according to the NIH COVID-19 guidelines. Clinical characteristics and outcomes were assessed. Individuals were grouped into solid organ transplant recipients, solid tumors, liquid tumors, and stem cell transplant recipients. Proportions were calculated per group in addition to the exact binomial confidence intervals (95%).

Results

We identified 39 pediatric aged patients ranging from 7 months to 20 years of age with a median age of 10. 35.9% (14/39) of individuals were solid organ transplant recipients, 25.6% (10/39) had solid tumors, 33% (13/39) had liquid tumors, and 5% (2/39) were stem cell transplant recipients. 17.9% were asymptomatic, 66.7% had mild disease, and 15.4% had severe/critical COVID-19 disease. The median time of positive SARS CoV-2 RT-PCR was 32 days. Six children had prolonged SARS-CoV-2 RT-PCR positive testing between 29-97 days with a mean of 49 days. Viral strand specific RNA testing for replicating virus was also persistently positive. Six experienced severe/critical disease resulting in death of three. Most of the patients were treated with predominantly T cell depleting agents (∼74%). However, four patients who had prolonged active critical infection were treated with B cell depleting agents or had known B cell dysfunction.

Conclusion

The majority of the immunocompromised children in our cohort had mild COVID-19 disease. A subset of individuals experienced ongoing prolonged RT-PCR positivity and testing indicating persistent viral replication, with three demonstrating an inability to control the virus and resulting in death. Worse outcomes may be related to their immune dysfunction and use of B cell depleting agents.

Disclosures

All Authors: No reported disclosures.
1108. Feasibility and Impact of a Monoclonal Antibody Infusion Program in Reaching Vulnerable Underserved Communities
Authors: Mena Lora Alfredo J , Herald Fischer , Lindsey Brenna , Echeverria Stephanie , Li Ella , Sanchez Lawrence , Truesdell Tiffany , Takhsh Eden , Lavani Romeen , Burgos Rodrigo M
Published: December 2022

Background

Monoclonal antibodies (mAbs) against SARS-CoV-2 are potent therapeutics that prevent progression of disease in high-risk patients. Deploying mAb infusion programs and reaching communities in need remains challenging. We established a mAb infusion program centered in the emergency department (ED) fast-track. We seek to assess the feasibility and impact of our mAb infusion program in reaching vulnerable underserved communities.

Methods

The ED fast-track was repurposed for mAb infusions. Indications and protocols were created by the infectious disease (ID) physician and antimicrobial stewardship program (ASP). Test to treat was deployed in the ED and a referral program connected patients from telehealth and providers in the community to the infusion program (Figure 1). Data on mAb use from November 2020 to February 2022 was reviewed. To assess the reach of the program in vulnerable communities, the COVID-19 Community Vulnerability Index (CCVI) map by zip code was used. The CCVI identifies communities at risk by using variables such as sociodemographic variables, occupational factors, cumulative COVID-19 burden, vaccine uptake and other factors. Figure 1.Monoclonal antibody infusion test-to-treat and referral process in the ED fast track

Results

mAbs were successfully deployed and sustained throughout the pandemic, increasing its use in each COVID-19 surge by >103% (Figure 2). A total of 267 patients were treated, with an average age of 52 years, of which 55% (147) were female. Ethnicity was 46% Hispanic and Race was 54% White, 28% Black, 1.4% Asian, 1.8% Multiracial and 14% Other. Zip codes by CCVI were 64% high, 18% medium, and 3% low CCVI index. 15% were outside of city limits without CCVI index (Figure 3). Figure 2.COVID-19 Community Vulnerability Index (CCVI) of patients who received monoclonal antibodies at our program

Figure 3 Monoclonal antibody infusions by COVID-19 Community Vulnerability Index (CCVI) and Zip codes

Conclusion

A mAb infusion program with test to treat and referrals from the community was successfully deployed in an ED fast track. The ED space and staff can be leveraged for mAbs during surges amid clinic staffing challenges. The program adopted novel mAbs as new COVID-19 variants emerged. Uptake increased with each wave, likely reflecting awareness of mAbs and the infusion program by patients and providers in the community. The majority of patients served (82%) were of high and medium CCVI. Thus, this mAb infusion program led by ID and ASP successfully reached predominantly underserved vulnerable populations.

Disclosures

All Authors: No reported disclosures.
1111. Baricitinib versus Tocilizumab for Hospitalized Adults with Severe COVID-19 in a Community Health System: A Retrospective Cohort
Authors: Gonzalez Alexandra , Martinez Aileen , Cardona Lyssette L , Hernandez-Jimenez Jarelys
Published: December 2022

Background

Severe coronavirus disease 2019 (COVID-19) is associated with respiratory failure as well as thromboembolic and cardiovascular complications from dysregulated immune responses. Baricitinib (BAR), a Janus kinase (JAK) inhibitor, and tocilizumab (TZB), a monoclonal anti-interleukin-6 (IL-6) receptor antibody, earned Emergency Use Authorizations (EUA) from the Food and Drug Administration (FDA) for the treatment of COVID-19. This study aims to compare the effects of BAR and TZB in severe COVID-19.

Methods

A retrospective chart review of patients admitted to Cleveland Clinic Martin Health with COVID-19 having received TZB or BAR was completed between 07/01/20 to 12/31/21. Exclusion criteria included patients who had received both agents in the same admission, received fewer than 5 doses of remdesivir, or were pregnant. The primary objective was to evaluate in-hospital mortality. For secondary outcomes, hospital length of stay (LOS), intensive care unit LOS, readmission due to respiratory-related causes, progression to mechanical ventilation (MV) and CRP levels upon discharge or death were assessed. Safety outcomes were described by incidences of superimposed bacterial infections, thrombosis, and herpes simplex virus reactivation.

Results

After adjustment of sex and CRP level, the odds of death in TZB was 86% higher than that of BAR group (OR 1.86, 95%CI 1.17-2.96, p=0.009). TZB group had more females (45% vs. 34%, p=0.036) and longer LOS (median [IQR]: 15 [10,23] vs. 13 [9,20], p=0.0390). TZB group had more organ support (47% vs. 29%, p< 0.001), more ICU admission and longer ICU LOS, more MV progression and longer duration of MV (36% vs. 22%, p=0.007; 0[0,9] vs. 0[0,2], p< 0.001). TZB had more additional source of infection (25% vs. 16%, p=0.043) and more positive microbiology from blood (10% vs. 3%, p=0.009).

Conclusion

Our findings suggest that BAR may have lower rates of in-hospital mortality when compared to TZB. TZB was also found to have higher needs for organ support. Superimposed infections, thrombosis, and HSV reactivation were similar in both groups. Larger randomized studies comparing these agents are needed.

Disclosures

All Authors: No reported disclosures.
1131. Evaluation of drug-drug interaction potential of ensitrelvir for CYP3A by clinical studies and physiologically-based pharmacokinetic model
Authors: Shimizu Ryosuke , Horiuchi Kana , Koshimichi Hiroki , Matsuzaki Takanobu , Yoshida Shinpei , Sakamoto Shingo , Kubota Ryuji
Published: December 2022

Background

Ensitrelvir is a new drug candidate to treat COVID-19 disease. According to the in vitro drug-drug interaction (DDI) study, time-dependent inhibition by ensitrelvir was observed on cytochrome P450 3A (CYP3A). The purpose of this study was to evaluate the effect of ensitrelvir on the pharmacokinetics (PK) of CYP3A substrates by clinial DDI studies and physiologically-based pharmacokinetic (PBPK) analyses.

Methods

Clinical studies: The effect of once daily multiple-doses of ensitrelvir with the loading dose on Day 1/ maintenance dose (750/250 mg) for 6 days on the PK of midazolam (MDZ) was assessed. MDZ was administered on Days -2 and 6. The effects of once daily multiple-doses of ensitrelvir with 750/250 mg for 5 days on the PK of dexamethasone (DXS) and prednisolone (PLS) were also assessed because these corticosteroids were also CYP3A substrates. DXS and PLS were administered on Days -2, 5 (co-administration with ensitrelvir), 9 and 14 to evaluate the effects after the last dose of ensitrelvir.

PBPK analyses: The effects of once daily multiple-doses of ensitrelvir with another dose regimen (the loading dose/mentenance dose [375/125 mg] for 5 days) on the PK of CYP3A substrates were predicted using Simcyp PBPK Simulator (Version 20, Certara UK Limited, UK).

Results

The AUC0-inf of MDZ co-administered with ensitrelvir was increased by 8.80-fold compared to those of MDZ alone, indicating that ensitrelvir is a strong CYP3A inhibitor with 750/250 mg for 6 days. The AUC0-inf of DXS on Day 5 was increased 3.47-fold and the effect of ensitrelvir on the PK of DXS was diminished over time after the last dose of ensitrelvir. The AUC0-inf of PLS on Day 5 was increased 1.25-fold and no clinically meaningful effect of ensitrelvir on the PK of PLS was observed. The PBPK analyses predicted that the co-administration of ensitrelvir increased the AUC of MDZ by 3.83-fold and the AUC of DXS by 2.49-fold following ensitrelvir at 375/125 mg for 5 days. A clinical study with MDZ under the analyses conditions is underway to confirm the PBPK results.

Conclusion

The clinical study revealed that ensitrelvir affects the PK of CYP3A substrates with 750/250 mg for 5 or 6 days. The PBPK analyses suggests that ensitrelvir is expected to a moderate inhibitor of CYP3A with 375/125 mg for 5 days.

Disclosures

Ryosuke Shimizu, Shionogi & Co., Ltd.: employee Kana Horiuchi, Shionogi & Co., Ltd.: employee Hiroki Koshimichi, n/a, Shionogi & Co., Ltd.: employee Takanobu Matsuzaki, Ph.D., Shionogi & Co., Ltd.: Employee Shinpei Yoshida, Ph.D., Shionogi & Co., Ltd.: employee Shingo Sakamoto, n/a, Shionogi & Co., Ltd.: employee Ryuji Kubota, Ph.D., Shionogi & Co., Ltd.: employee|Shionogi & Co., Ltd.: employee.
1136. No Change of Pharmacokinetics of Metformin by Concomitant Use of Ensitrelvir
Authors: Horiuchi Kana , Koshimichi Hiroki , Matsuzaki Takanobu , Shimizu Ryosuke , Yoshida Shinpei , Kubota Ryuji , Sakamoto Shingo
Published: December 2022

Background

Ensitrelvir is a novel oral SARS-CoV-2 3C-like protease inhibitor, and under late clinical development stage for COVID-19 diseases. Ensitrelvir exhibited an inhibition potency for organic cation transporter 1 (OCT1) and multidrug and toxin extrusion protein 1 (MATE1) in in vitro study and clinical drug-drug interaction (DDI) study is required judging from DDI guidance. Metformin is widely used for treatment of diabetes, and is a sensitive substrate for OCT1 and MATE1. We evaluated the effect of ensitrelvir on the pharmacokinetics (PK) of metformin with physiologically-based pharmacokinetic (PBPK) modeling and simulation and clinical DDI study.

Methods

The PBPK model of ensitrelvir was developed based on the physicochemical parameters, in vitro transporter inhibition parameters, and estimated PK parameters for human. DDI simulations between ensitrelvir and metformin were performed. Simcyp PBPK Simulator (Version 20, Certara UK Limited, UK) was used to develop PBPK model and simulate the DDIs. The in vitro 50% inhibitory concentration (IC50) values of each transporter were used as inhibition constant (Ki) for DDI simulations. Based on the PBPK analysis, the clinical DDI study planed.

Results

PBPK analysis: As the result of DDI simulation, ensitrelvir increased the area under the curve (AUC) of metformin by 12%. The result suggests that in vivo DDI potency of ensitrelvir via inhibition of OCT1 or MATE1 would be low at a single dose of ensitrelvir 1000 mg.

Clinical DDI study: The plasma concentration-time profile of metformin and ensitrelvir were monitored after 96 hours from a single dose of metformin with or without ensitrelvir. Ensitrelvir does not have effect on the PK of metformin (a geometric mean of AUC ratio was 1.02, Japanese healthy subjects, N=14), suggesting no MATE1 and OCT1 inhibition by ensitrelvir at a clinical dose. The PBPK analysis could well predict the clinical DDI study result.

Conclusion

The results of PBPK analysis and the clinical DDI study suggest that no OCT1 and MATE1 inhibition by ensitrelvir is in the clinical dose. Therefore, ensitrelvir does not have a clinically meaningful effect on the pharmacokinetic profile of OCT1 and/or MATE1 substrates including metformin.

Disclosures

Kana Horiuchi, Shionogi & Co., Ltd.: employee Hiroki Koshimichi, n/a, Shionogi & Co., Ltd.: employee Takanobu Matsuzaki, Ph.D., Shionogi & Co., Ltd.: Employee Ryosuke Shimizu, Shionogi & Co., Ltd.: employee Shinpei Yoshida, Ph.D., Shionogi & Co., Ltd.: employee Ryuji Kubota, Ph.D., Shionogi & Co., Ltd.: employee|Shionogi & Co., Ltd.: employee Shingo Sakamoto, n/a, Shionogi & Co., Ltd.: employee.
1138. Optimal Duration of Systemic Corticosteroids Use in COVID-19 Treatment: A Meta-analysis
Authors: Yu Nyein , Ssentongo Paddy , Ingram David , Paules Catharine I
Published: December 2022

Background

Corticosteroids confer a survival benefit in hospitalized COVID-19 patients requiring oxygen, but optimal treatment duration remains uncertain. The goal of this meta-analysis is to determine the optimal duration of corticosteroids in the treatment of severe COVID-19. Figure:The effect of systemic steroids on mortality stratified by the duration of treatment in days.

The greatest survival benefit was observed for the treatment duration of up to 6 days (A). No survival benefit was observed beyond 7 days of treatment (B).

Methods

Electronic databases (MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, the World Health Organization Global Literature on Coronavirus Disease, CoronaCentral, and Web of Science) and trial registries were searched to March 9, 2022, for randomized controlled trials and observational cohort studies reporting corticosteroid versus no corticosteroid treatment in hospitalized COVID-19 patients. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomized controlled trials) or the Newcastle-Ottawa Scale (observational studies). We estimated the effect of corticosteroids on mortality by random-effects meta-analyses using the generic inverse variance method. Subgroup analyses and meta-analyses were conducted to assess the optimal duration of corticosteroid treatment.

Results

We identified 28 eligible studies consisting of 13,404 hospitalized COVID-19 patients. Median age was 62 years (interquartile range: 59 – 67), and 65% were male. Eight randomized controlled trials and 20 observational studies were included in the meta-analysis of mortality, which suggested a protective association with corticosteroid therapy (risk ratio, 0.75; 95% CI: 0.64; 0.87). Pooled analysis of 19 studies showed the greatest survival benefit for a treatment duration up to 6 days (risk ratio, 0.54; 95% CI, 0.39; 0.74). Survival benefit was 0.68 (95% CI, 0.57; 0.82) up to 7 days, and no survival benefit was observed beyond 7 days of treatment (risk ratio, 0.71; 95% C: 0.51; 1.01).

Conclusion

In this meta-analysis, the optimal duration of corticosteroid treatment for hospitalized COVID-19 patients was up to 6 days, with no additional survival benefit with > 7 days of treatment. Future analyses should stratify survival benefit by baseline disease severity to see if subgroups of patients derive greater benefit from longer courses of steroids.

Disclosures

All Authors: No reported disclosures.
1140. Outcomes and Complications of Tocilizumab and Baricitinib use in Transplant Patients with COVID-19
Authors: Mendoza Maria A , Razonable Raymund R , Abu Saleh Omar M
Published: December 2022

Background

Immunomodulators have been shown to improve the outcomes of patients with severe COVID-19. However, it is not known if tocilizumab or baricitinib use would be beneficial in transplant patients who are already receiving immunomodulating agents. Moreover, augmented immunomodulation may increase risk of opportunistic infection. There are few studies analyzing the outcomes and complications of these medications in this population.

Methods

This is a detailed review of the medical records of all transplant patients who received tocilizumab or baricitinib for COVID-19 indication at our multi-state transplant center from April 2020 to March 2022.

Results

A total of 57 transplant patients received tocilizumab (n=48) or baricitinib (n=9) for management of COVID-19. Baseline characteristics are in Table 1. 60% had received at least one dose of COVID-19 vaccine. At diagnosis, all patients were lymphopenic (median 0.4 x109 cells/L) with high CRP (median 76.8mg/L) and elevated IL-6 levels (median 145.5pg/ml.). The majority had reduction in transplant immunosuppression (75%) and received remdesivir (86%) and dexamethasone (90%). Majority were admitted to the ICU (68%), including 40% who required invasive mechanical ventilation (Table 2). Almost a third developed bacterial or fungal superinfection. Bacterial infections include respiratory cultures with Klebsiella spp, MRSA, P. aeruginosa, Enterobacter spp and Stenotrophomonas. Blood cultures were positive for Klebsiella spp, MDR P. aeruginosa, E faecalis. Fungal infections include three patients with Aspergillus spp infections who received antifungals. No statistical difference was seen in mortality between patients with infections and not infections group. No statistical difference was seen between type of transplants for infection or mortality. Mortality at 90 days was 46%.

Conclusion

Transplant patients who received tocilizumab or baricitinib for severe or critical COVID-19 have poor outcome. This case series found high rates of mortality and opportunistic superinfections after tocilizumab and baricitinib use compared to the current literature. Future directions include a matched case-control study to compare the outcomes in this population.

Disclosures

Raymund R. Razonable, MD, Gilead: Grant/Research Support|Glaxo Smith Kline: Advisor/Consultant|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support.