bluuebunny/crossref_metadata_2025_split huggingface dataset:
503. In vitro Evaluation of Sitagliptin-HIV-1 Trans-activator Transcription Peptide Nano-formula for Antiviral Activity Against SARS-CoV-2: Drug Repurposing Approach
Authors: Eljaaly Khalid , Asfour Hani , Ibrahim Tarek , Ahmed Osama , Alhakamy Nabil , Fahmy Usama , Al-Rabia Mohammed , Aloafi Ahmed , Tantawy Mohamed , Hussein Khulood , Aldarmani Ahmed , Elfaky Mahmoud 
Published: December 2021

Abstract

Background
The outbreak of COVID-19 pandemic in China regarded as a major health/economic hazard. The importance of coming up with mechanisms for preventing or treating COVID-19 has been felt across the world. This work aimed at examining the efficiency of Sitagliptin (SIT) and human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) against SARS-CoV-2.

Methods
SIT-TAT nano-conjugates were prepared according to a full three-factor bi-level (23) factorial design. SIT concentration (mM, X1), TAT concentration (mM, X2), and pH (X3) were selected as the factors. Particle size (nm, Y1) and zeta potential (mV, Y2) were assessed as responses. Characterization of the optimized formula for Fourier-transformed infrared (FTIR) and Transmission electron microscope was carried out. In addition, IC50 in Vero E6 cells, In vitro 3CL-protease inhibition and docking tests were investigated.

Results
The prepared complex’s formula was as follows 1: 1 SIT: TAT molar ratio, whereas zeta potential and particle size values were at 34.17 mV and 97.19 nm, respectively. This combination did exhibit its antiviral potentiality against SARS-CoV-2 via IC50 values of 9.083 5.415, and 16.14 µM for TAT, SIT-TAT, and SIT, respectively. In addition, the complex SIT-TAT showed a significant (P &lt; 0.001) viral-3CL-protease inhibitory effect (IC50 = 3.959 µM ± 0.011) in comparison to isolated components (IC50 = 10.93 µM ± 0.25) and TAT (IC50 = 8.128 µM ± 0.42). This was further confirmed via in silico study. Molecular docking investigation has shown promising binding affinity of the formula components towards SARS-CoV-2 main protease (3-CL).

Conclusion
While offering significant binding interactions with protein’s key pocket residues, an optimized formulation of SIT-TAT could guarantee both the enhanced delivery to the target cells and the improved cellular uptake. The presented findings would guarantee further investigations regarding formula optimization against SARS-CoV-2.

Disclosures
All Authors: No reported disclosures
504. Case SEries: Nasal Antimicrobial Photodisinfection (APDT) as Treatment Protocol for Asymptomatic and Early Stage COVID-19 Patients
Authors: Kolenda Jack , Argemi Josepmaria 
Published: December 2021

Abstract

Background
Targeted reduction of SARS-CoV-2 viral load in the nose may mitigate the severity of lower tract respiratory disease as well as reduce hospitalization and mortality rates. Nasal Photodisinfection has been deployed for 10 years in Canadian hospitals reducing post-surgical infections. The objective of thiswork was to demonstrate effectiveness of APDT in early stage COVID-19 and asymptomatic carriers.

Methods
A cohort of 40 COVID-19 positive patients were treated with nasal photodisinfection (Steriwave) at a private clinic. All patients were previously identified by PCR as SARS-CoV-2 positive and admitted into the treatment cohort. BD rapid antigen nares testing was used before and after Photodisinfection treatment. Of the 40 patients, 13 were female and 27 were male. Age range was 9- 56 years of age. Treatment involved 3-4 applications of photosensitizer and 16-24 minutes per patient of treatment time. Patients were followed up within 24 hours, 48 hours as well as day 5 and 6 and day 10/11. Patients filled out a COVID-19 score card.

Results
Results demonstrated APDT was capable of significant and rapid viral load reduction in COVID-19 carriers. 100% of patients were converted from positive rapid antigen test to negative. 60% of patients reported fever resolution within 24 hours. Fever resolution occurred in 100% of patients within 48hours. Moreover, results demonstrated accelerated resolution of COVID-19 symptoms and significantly improved mental health benefits from reduction of COVID-19 related stress and anxiety. None of the patients experienced severe symptoms and no patients were hospitalized. Safety outcomes demonstrated no patient safety issues with only minor transient side effects (rhinorrhea, sneezing) observed. Moreover, the treatment procedure was pain-free and well tolerated by all patients.

Conclusion
Photodisinfection-based nasal decolonization anti-viral efficacy was demonstrated with improved outcomes for all patients treated in this case series. Significant rapid viral load reduction was confirmed by rapid antigen tests in all patients. More clinical studies are warranted in support of Photodisinfection based therapy for upper respiratory infections such as COVID-19.

Disclosures
All Authors: No reported disclosures
506. Outpatient Bamlanivimab, Casirivimab and Imdevimab for COVID-19: Single Center Feasibility Analysis
Authors: Chundi Vahini , Wenner Jennifer J , Scheib Christopher , Patel Yatin , snider Cynthia , Hatcher Jeffrey C , McQuaid Douglas B 
Published: December 2021

Abstract

Background
Monoclonal Antibodies directed at the spike protein of SARS-COV-2 are approved by the FDA for Emergency Use for outpatients with COVID- 19 who are at risk for severe complications. Here we present a single center experience using Bamlanivimab and Casirivimab/Imdevimab to prevent hospitalizations due to SARS-COV-2.

Methods
Adult patients who tested positive for SARS-COV-2 in our health system were offered outpatient monoclonal antibody infusion if: (1) testing was done within the previous 7 days, (2) the patient had fewer than 10 days of symptoms, (3) the patient was not currently hospitalized, and (4) met at least 1 of 8 criteria in the FDA EUA Fact Sheet for Bamlanivimab and Casirivimab/Imdevimab. Patients who met the criteria were offered the monoclonal antibody available at time of infusion. Those who declined antibody infusion were used as potential controls. The primary outcome was the discrepancy in hospitalization rates at 14-days past the infusion date for patients receiving the monoclonal antibody regimen versus 14-days past when those in control group would have been scheduled for infusion had they accepted. Secondary outcomes included emergency room visits, duration of hospitalization, and Intensive Care Unit stays. Coarsened exact matching (CEM) was used to obtain balance between treatment and control groups. A logistic regression model measured statistical differences between the groups.

Results
Between November 23, 2021 and February 8, 2021, 5567 patients were offered a monoclonal antibody infusion. A total of 894 patients completed infusion who were able to be matched with patients in the control group. Patients who received the infusion were statistically less likely to be hospitalized than those who did not receive the infusion (2.68% vs 6.70%, p&lt; 0.001).

Conclusion
This feasibility study shows reduction in hospitalization in patients who received monoclonal antibody versus standard care. It provides real-world information regarding using monoclonal antibodies as a tertiary prevention strategy to limit the progression of SARS-CoV2 infections, which will lead to improved clinical outcomes and decreased healthcare costs.

Disclosures
All Authors: No reported disclosures
507. Impact of Baricitinib on Outcomes in Patients Treated with Remdesivir and Dexamethasone for SARS-CoV-2 Pneumonia: A Retrospective Cohort Study
Authors: Dea Lauren , Piwonka Hal , Gonzales Learned , Kerkar Shubha , Mdluli Xolani , Kim Yisu 
Published: December 2021

Abstract

Background
There is a lack of data specifically addressing the effects of triple therapy consisting of baricitinib plus remdesivir plus dexamethasone compared to dual therapy with remdesivir plus dexamethasone among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia.

Methods
This retrospective study enrolled hospitalized adults with SARS-CoV-2 receiving supplemental oxygen without invasive mechanical ventilation (IMV) being treated baricitinib (≤10 days) plus remdesivir (≤10 days) plus dexamethasone (≤10 days) or remdesivir (≤10 days) plus dexamethasone (≤10 days). The primary endpoint was 28-day mortality. Secondary objectives of this study were to measure progression to IMV, pulse oximetry (SpO2)/fraction of inspired oxygen (FiO2) from hospitalization to discharge, hospital length of stay (LOS), 14-day mortality, 14-day hospital readmissions, inflammatory markers, and safety outcomes.

Results
Among patients receiving supplemental oxygen without IMV, 28-day mortality for triple therapy vs. dual therapy was 20% and 24%, respectively (P=1.000). The effect of triple therapy compared to dual therapy on lung function was demonstrated by a 76% vs. 25% increase in SpO2/FiO2. This benefit must be contextualized by an increased progression to IMV among patients receiving triple therapy compared to dual therapy (10 patients [50%] vs. 7 patients [28%], respectively; P=0.130). The increased incidence of IMV translated to a significantly longer hospital LOS among patients receiving triple therapy compared to dual therapy (26 days vs. 17 days, respectively; P=0.001).

Conclusion
In patients receiving supplemental oxygen without IMV for SARS-CoV-2, triple therapy was not associated with a clinically meaningful reduction in 28-day mortality when compared to dual therapy.

Disclosures
All Authors: No reported disclosures
510. Reduced Mortality Rate in Critically Ill Patients with COVID-19 with the Implementation of a Treatment Protocol—Experience of a Tertiary Care Center in the Midwest During the Initial Surge of COVID-19
Authors: Kaushik Ashlesha , Gupta Sandeep , Gupta Jitendra 
Published: December 2021

Abstract

Background
COVID-19 has been an unprecedented pandemic resulting in high mortality. We report our experience of using a treatment protocol in the intensive care unit (ICU) during the first peak of the pandemic.

Methods
All patients diagnosed with SARS-CoV-2 infection admitted to the ICU between April 14-June 14, 2020 were included. Remdesivir was made available for use in our institution on May 14th 2020, and thereafter, a treatment protocol combining remdesivir, corticosteroids and tocilizumab was implemented in the ICU, with doses as follows: Remdesivir 200mg intravenously (I.V.) on day 1, then 100 mg for 4 days; tocilizumab 400 mg I.V. once a day for 2 days; dexamethasone 6 mg I.V. daily for 10 days followed by taper. During pre-protocol period, patients were receiving hydroxychloroquine (400 mg once on day 1 followed by 200 mg twice daily orally for 4 days). We compared the pre-protocol period (labeled as P1: April 14, 2020- May 13, 2020) with protocol period (P2: May 14, 2020 -June 14, 2020) for clinical outcomes.

Results
A total of 32 and 48 patients were included during P1 and P2 respectively. Both groups were similar in terms of demographic characteristics, mean (±SD) age [55(±10) and 54 (±12) years] and mean Charlson-Deyo risk score at admission [2.4(±0.8) and 2.5 (±0.9) respectively]. During both periods, a comparable number of patients needed mechanical ventilation (65% and 66% respectively), anticoagulation (74% and 76% respectively) and inotropes (41% and 40%). The mean duration of ICU stay during P1 was significantly longer than P2 [15.4 (±2.8) days versus 9.3 ± (3.8) days, p&lt; 0.0001)]. During P1, mean duration of mechanical ventilation [10 (±1.6) days] was also significantly longer than P2 [7.1 (±2.7) days] (p= 0.0004). There was a significant reduction in mortality rate from 68% (22/32) during P1 to 10.4% (5/48) in P2 (p&lt; 0.0001). Patients were 4.3 times more likely to die during P1 than P2 (95% CI= 2.47-7.86).

Conclusion
Our results showed a decrease in ICU mortality rate by 57.6% with the implementation of a treatment protocol combining remdesivir, tocilizumab and corticosteroids during the first months of the initial surge of the pandemic, with a significant decline in length of ICU stay and duration of mechanical ventilation; and support the therapeutic data endorsed by IDSA/NIH guidelines.

Disclosures
All Authors: No reported disclosures
512. Does Time From COVID-19 Symptom Onset to Administration of Anti-spike Protein Monoclonal Antibody Predict Response?
Authors: SanFilippo Savanna , Crovetto Brynna , Milano Marc , Bucek John , Nahass Ronald G , Brunetti Luigi 
Published: December 2021

Abstract

Background
Casirivimab/imdevimab is a monoclonal antibody (mAb) cocktail with emergency use authorization for mild-to-moderate coronavirus disease 2019 (Covid-19) in patients at high risk for severe disease progression and/or hospitalization. Little is known about the importance of early administration of this product. The objective of this study was to determine if early administration (within 3 days of symptom onset) of casirivimab/imdevimab is associated with better outcomes.

Methods
Single-center, retrospective cohort study including all consecutive patients who received casirivimab/imdevimab at our institution through May 2021. The primary outcome was 30-day post-infusion hospital admission rate in patients who received mAb ≥ 3 days (later) or &lt; 3 days (early) in relation to patient reported symptom onset. Secondary outcomes included any hospital revisit within 30-days. Adverse events were also captured. Chi-square and independent samples t-test were used to compare categorical and continuous data, respectively. Multivariable logistic regression was used to adjust for confounders.

Results
270 patients met the inclusion criteria and were included in the analysis. There were 80 patients with early administration and 190 with later administration. Baseline characteristics for both groups were similar. Mean age was approximately 64 years and BMI 31 mg/m2. Table 1 provides a summary of patient characteristics. Late and early administration of casirivimab/imdevimab were similar in terms of hospital admission for any therapy related failure within 30 days of mAb administration after adjusting for age and Charlson comorbidity index (3.7% vs. 7.5%; adjusted odds ratio 0.69, 95% confidence interval, 0.20 – 2.39; p=0.561). Similarly, there were no significant differences in any hospital revisit.

Conclusion
We did not find any difference in outcomes between early and late administration of casirivimab/imdevimab.

Disclosures
Ronald G. Nahass, MD, Abbvie (Grant/Research Support, Speaker’s Bureau)Alkermes (Grant/Research Support)Gilead (Grant/Research Support, Speaker's Bureau)Merck (Grant/Research Support, Speaker's Bureau)
513. Use of Antimicrobial Stewardship Program in Operationalizing Monoclonal Antibody Therapy in SARS-CoV-2 Infection
Authors: Abrantes-Figueiredo Jessica , Nalewyko Stephanie , Wiskirchen Dora E 
Published: December 2021

Abstract

Background
Antimicrobial stewardship programs (ASP) have been essential during the coronavirus disease 2019 (COVID-19) pandemic response. Use of monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has proven difficult to operationalize, despite being available through emergency use authorization (EUA). Utilizing existing ASP and multidisciplinary approach to lead the effort, we aim to describe our experience in operationalizing monoclonal antibody therapy.

Methods
Retrospective study of SARS-CoV-2 infected adults receiving monoclonal antibody therapy under EUA (December 2020-April 2021). An algorithm developed by the ASP provided education and an interactive online tool allowing referring physicians and patients to assess eligibility prior to hospital arrival. Patients were screened and approved by existing ASP which included; Infectious Disease (ID) physicians, pharmacist, and ID Nurse. A multidisciplinary approach with ER staff and development of pharmacy workflow with order set were utilized as eligible patients received infusion in dedicated ER location. Data such as demographics, co-morbid condition, infusion related complications, hospitalization, and death were reviewed and collected regularly by the ASP team with frequent monitoring and regulatory reporting. Primary patient outcome was preventing hospitalization.

Results
107 patients received monoclonal antibody therapy. 47% patients were male, 50% White, and 79% non-Hispanic. 87% received monotherapy (bamlanivimab) and 13% received dual therapy (bamlanivimab/etesevimab). 17 patients required hospitalization post infusion. 1 death occurred. COVID-19 related hospitalization within 30-days was avoided in 84% of treated patients. No adverse event directly related to infusion were seen.

Conclusion
Use of monoclonal antibody therapy under EUA for patients for SARS-CoV-2 infection led to decrease in hospitalization in this cohort. An existing ASP using an algorithmic approval process, frequent monitoring, and multidisciplinary approach successfully operationalized the use of monoclonal antibody therapy. ASP’s provide benefit and versatility beyond monitoring of antimicrobials alone and should continue to receive support by hospital leadership.

Disclosures
All Authors: No reported disclosures
514. Anti-SARS-CoV-2 Monoclonal Antibodies for Early COVID-19: A Real World Experience
Authors: Belden Katherine , Hess Bryan , Brugger Caroline , Carr Rachel , Braun Todd , DeRose Joseph L , Zurlo John 
Published: December 2021

Abstract

Background
Anti-SARS-CoV-2 monoclonal antibodies afford prompt immunity, have demonstrated reduction in severe COVID-19 in high risk ambulatory patients, and are available through Emergency Use Authorization. Challenges exist, however, to widespread utilization.

Methods
This operations study 11/23/20-4/30/21 identified patients meeting monoclonal AB EUA criteria by test results or referral. Outreach to harder-hit neighborhoods included connecting with primary care teams and testing sites. Infusion centers with staff trained in infection control, rapid response and drug preparation were utilized. The primary study outcome was treatment of qualifying patients. Secondary outcomes included infusion complications, hospitalization/death, and symptom resolution. Investigational review board approval was obtained.

Results
367 patients were treated: mean age of 63, 201(55%) male, 276(75%) white, 54(15%) black. All patients had a first positive direct SARS-CoV-2 test within 10 days, 232(63%) had &gt; 1 high-risk qualification, 32(9%) were vaccinated for SARS-CoV-2. Of patients with available zipcodes, 135(38%) had a Community Need Index &gt;3.5 and 157(45%) a Social Vulnerability Index &gt;0.5. 190(52%) received bamlanivimab, 93(25%) casirivimab/imdevimab, 84(23%) bamlanivimab/etesevimab. Four patients experienced infusion reaction, 1 with anaphylaxis. 172(73%) of 236 patients were symptom free at day 5. 20 patients (5%) were hospitalized for COVID-19 within 30 days with a median time from symptom onset to infusion of 7 days, 11(55%) were admitted within 24 hours, 1 died.
Patient Characteristics

COVID-19 course

Community Need Index and Social Vulnerability Index by Zipcode

Conclusion
Our study demonstrates that treatment with anti-SARS-CoV-2 monoclonal antibodies is feasible in a high resource setting. There were no related SARS-CoV-2 exposures and therapy was well tolerated. Trials of anti-SARS-CoV-2 monoclonal antibodies have reported lower rates of hospitalizations in treated patients than we found. This may reflect the expanded time frame for EUA therapy as compared to clinical trials, differences in real world patients or viral variants. Given potential benefit in unvaccinated patients or those at risk for poor vaccine response, the equitable utilization of anti-SARS-CoV-2 monoclonal antibody therapy in early COVID-19 should remain a focus for researchers and clinicians.

Disclosures
All Authors: No reported disclosures
515. Evolution of Treatment Patterns for Patients Hospitalized with COVID-19 in the United States
Authors: Zalocusky Kelly , Rizzo Shemra , Chawla Devika , Chia Yifeng , Kamath Tripthi , Tsai Larry 
Published: December 2021

Abstract

Background
COVID-19 remains a threat to public health, with over 30 million cases in the US alone. As understanding of optimal patient care has improved, treatment guidelines have continued to evolve. This study characterized real-world trends in treatment for US patients hospitalized with COVID-19, stratified by whether patients required invasive ventilation.

Methods
US patients diagnosed and hospitalized with COVID-19 between March 23 and December 31, 2020, in the Optum de-identified COVID-19 electronic health record (EHR) data set were identified. Both drug and procedure codes were used to ascertain medications, and both procedure and diagnostic codes were used to detect invasive ventilation during hospitalization. Medication trends were estimated by computing proportions of hospitalized patients receiving each drug weekly during the study period.

Results
In this cohort of 71,366 hospitalized patients, the largest observed change in care was related to chloroquine/hydroxychloroquine (HCQ) (Figure). HCQ usage peaked at 87% of patients receiving invasive ventilation (54% without ventilation) in the first week of this study (March 23-29), but declined to &lt; 5% of patients, regardless of ventilation status, by the end of May. In contrast, dexamethasone usage was 10% at baseline in patients receiving ventilation (1% without ventilation) and increased to a steady state of &gt;85% of patients receiving ventilation ( &gt;50% without ventilation) by the end of June. Similarly, remdesivir usage increased sharply from a baseline of 2% of patients and continued to rise to a peak of 79% of patients receiving invasive ventilation (44% without ventilation) in November before declining.

Conclusion
Meaningful shifts in treatments for US patients hospitalized with COVID-19 were observed from March through December 2020. A dramatic decline was observed for HCQ use, likely owing to safety concerns, while usage of dexamethasone and remdesivir increased as evidence of their efficacy mounted. Across medications, usage was substantially more prevalent among patients requiring invasive ventilation compared with patients with less severe cases.

Disclosures
Kelly Zalocusky, PhD, F. Hoffmann-La Roche Ltd. (Shareholder)Genentech, Inc. (Employee) Shemra Rizzo, PhD, F. Hoffmann-La Roche Ltd. (Shareholder)Genentech, Inc. (Employee) Devika Chawla, PhD MSPH, F. Hoffmann-La Roche Ltd. (Shareholder)Genentech, Inc. (Employee) Yifeng Chia, PhD, F. Hoffmann-La Roche Ltd (Shareholder)Genentech, Inc. (Employee) Tripthi Kamath, PhD, F. Hoffmann-La Roche Ltd (Shareholder)Genentech, Inc. (Employee) Larry Tsai, MD, F. Hoffmann-La Roche Ltd (Shareholder)Genentech, Inc. (Employee)