bluuebunny/crossref_metadata_2025_split huggingface dataset:
516. Evaluation of COVID-19 Monoclonal Antibody Therapies for the Treatment of Non-hospitalized Patients with COVID-19
Authors: Morado Faiza , Nanda Neha 
Published: December 2021

Abstract

Background
In an effort to reduce strain on healthcare systems with patient hospitalizations and deaths due to COVID-19, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for 2 monoclonal antibodies for the treatment of COVID-19 in November 2020: bamlanivimab (BAM) and casirivmab-imdevimab (CAS-IMD). While clinical trial data demonstrated reductions in hospitalization rate, real-world data at the time of approval was vastly limited.

Methods
A retrospective chart review of non-hospitalized patients who received either BAM or CAS-IMD from November 27th, 2020 to February 16th, 2021. Variables included timing of monoclonal antibody infusion, adverse events, and 30-day hospitalization rate. Descriptive statistics were calculated for all data.

Results
101 patients received either BAM (75.2%) or CAS-IMD (24.8%) at a median of 6 days (IQR 4-7) from reported symptom onset. The most commonly reported symptoms of COVID-19 at time of referral were cough (57.4%), fever (29.7%), and myalgia (27.7%). All patients (100%) had at least 1 documented EUA defined risk factor for severe COVID-19 (Table 1). Following transfusion, 7/101 (6.9%) and 3/101 (3.0%) experienced mild to moderate and severe adverse events, respectively (Table 2). At day 30, 5 patients (5.0%) were hospitalized with COVID-19 at a median of 7 days (IQR 3-8) post monoclonal antibody infusion.

Conclusion
We observed a higher frequency of hospitalization compared to 1.6% for BAM in BLAZE-1 and 3% for CAS-IMD in REGN-COV-2. This observation may reflect our higher risk population as all patients presented with at least 1 risk factor for severe disease compared to 69.6% and 65.0% in BAM and CAS-IMD clinical trials, respectively. Additionally, patients presented with longer durations of symptoms prior to infusion in our study population compared to 3 days reported in BAM and 4 days reported in CAS-IMD trials. Since the conclusion of this study, the FDA revoked the EUA for BAM administered alone based on increased observations of resistant variants to BAM monotherapy. However, our observations highlight the need for further exploration in the prevention of hospitalization in high risk populations as well as the optimal timing of monoclonal antibody therapy.

Disclosures
All Authors: No reported disclosures
520. Pharmacokinetic and Safety Phase 1 Study and Microneutralization Assay Results with BRII-196/BRII-198, a Novel Antibody Cocktail Active Against a Wide Range of SARS-CoV-2 Variants
Authors: Margolis David A , Zhang Fujie , Hao Xiaohua , Li Yanyan , Wang Mingming , Li Chunming , Zhang Yao , Ma Ji , Ji Yun , Zhu Qing 
Published: December 2021

Abstract

Background
BRII-196 and BRII-198 are human monoclonal antibodies (mAb) with an extended half-life targeting distinct epitopes of the spike protein on SARS-CoV-2. Mutations in these epitope regions are continuously emerging, potentially conferring resistance to COVID-19 therapeutics in development. Individual phase I studies showed that BRII-196 or BRII-198 alone were safe and well tolerated in healthy subjects. The BRII-196 and BRII-198 cocktail is currently under evaluation in Phase 2/3 studies for the treatment of COVID-19.

Methods
Preclinical study: BRII-196 and BRII-198 were evaluated in the microneutralization assay using pseudo-viruses encoding mutations identified in the spike protein of a panel of SARS-CoV-2 variants of concerns, including strains originating in UK, SA, BR, CA, and India. The fold-change in neutralization IC50 titers relative to wild-type virus was calculated. Phase 1 study: healthy adults received sequential IV BRII-196 and BRII-198 (n=9) or placebo (n=3); and were followed for 180 days. Two dose levels (750mg/750mg and 1500mg/1500mg) were evaluated for safety, pharmacokinetics and immunogenicity. Interim analysis results are presented.

Results
Preclinical: BRII-196 and BRII-198 exhibited neutralizing activity against pseudo-virus variants that contained spike mutations of a panel of variants including B.1.1.7 (UK), B.1.351(SA), P.1(BR), B.1.427/429 (CA), B.1.526 (NY), and B.1.617 (IN), comparable to that against wild-type virus. Phase I study: BRII-196 plus BRII-198 was well tolerated with no dose-limiting adverse events (AEs), deaths, serious adverse events, or infusion reactions. The majority of AEs were isolated asymptomatic grade 1-2 laboratory abnormalities. (Table 1). Each mAb displayed pharmacokinetic characteristics expected of extended half-life YTE-antibodies.

Conclusion
The BRII-196 and BRII-198 cocktail was well-tolerated, and maintains neutralization against currently reported circulating variants of concern. These preclinical and clinical results support further development of BRII-196 and BRII-198 as a therapeutic or prophylactic option for SARS-CoV-2.

Disclosures
David A. Margolis, MD MPH, Brii Biosciences (Employee) Yao Zhang, MD, Brii Biosciences (Employee) Yun Ji, PhD, Brii Biosciences (Employee, Shareholder)
521. Predictors of Hospitalization Due to Coronavirus Disease 2019 (COVID-19) at a Veterans Affairs Medical Center
Authors: Ho Macy , Le Sarah , Sevak Rajkumar J , Chapman-Bueno Jamie G , Berman Stephen M , Chun Patricia , Moon Yong S 
Published: December 2021

Abstract

Background
During the COVID-19 pandemic, the Veterans Affairs Long Beach Healthcare System (VALB HCS) saw a surge of patients with a positive SARS-CoV-2 test. There is a lack of guidance on triaging patients with COVID-19 in the clinical literature. To address this need, our study evaluated factors that predicted hospitalization of patients due to COVID-19.

Methods
This was a retrospective cohort study of patients with a positive SARS-CoV-2 test and medical evaluation at the VALB HCS between August 1 and December 31, 2020. SARS-CoV-2 positive patients admitted to the hospital for a non-COVID-19 related diagnosis were excluded. At the time of initial evaluation, demographic, clinical, and laboratory data, and PCR cycle threshold were collected and compared between patients admitted to the hospital and those managed in the community. A multiple logistic regression analysis was conducted to evaluate predictors for hospitalization due to COVID-19.

Results
Of 748 patients, 94 were admitted to the hospital and 654 were community-managed. The outcomes from the logistic regression analysis indicated that the model explained 58.8% of variance and was a significant predictor of hospitalization (X2 [8, 737] = 277.5, p&lt; 0.0001). Patients with self-reported shortness of breath (OR=12.14, 95% CI=6.43-22.92) or diarrhea (OR=2.78, 95% CI=1.33-5.84) were more likely to be hospitalized, whereas patients with sore throat (OR=0.095, 95% CI=0.017-0.53) or body ache (OR=0.42, 95% CI=0.20-0.89) were less likely to be hospitalized than patients not having such symptoms. Every unit increase in patients’ age and temperature increased the likelihood of hospitalization by 7.6% and 62.7%, respectively. Every unit increase in patients’ diastolic pressure and SpO2% decreased the likelihood of hospitalization by 6.1% and 3.6%, respectively.

Conclusion
Our findings indicate that patients with shortness of breath, diarrhea, temperature, and old age were more likely to be hospitalized due to COVID-19. The results may help providers in clinical decision making regarding whether to admit the patient or not. These findings may be especially helpful when hospital bed availability is limited.

Disclosures
All Authors: No reported disclosures
522. Evaluation of Three COVID-19 Monoclonal Antibody Regimens in the Context of Rising B.1.526 Prevalence in New York City
Authors: Bao Hongkai , Guo Yi , Cowman Kelsie , Chen Victor , Nori Priya , Nori Priya 
Published: December 2021

Abstract

Background
Monoclonal antibodies were given emergency use authorization (EUA) by the Food and Drug Administration for the treatment of high-risk, outpatient COVID-19 infection. In New York City (NYC), the emergence and rapid growth of the B.1.526 variant of concern (VOC) possessing the E484K mutation was first noted in February 2021. In-vitro studies subsequently confirmed attenuated monoclonal antibody neutralization against VOCs. At our institution, bamlanivimab (BAM) alone or with etesevimab (B/E) and casirivimab/imdevimab (C/I) were utilized at different phases of the pandemic. The objective of this study was to assess their comparative efficacies in a highly variant prevalent setting.

Methods
This retrospective analysis was conducted at an urban hospital in the Bronx, NY and evaluated adult monoclonal antibody recipients from any of our infusion sites. Patients initially received BAM but given the high prevalence of variants, treatment was transitioned to first B/E and then C/I exclusively. We compared BAM versus combination therapy as well as B/E versus C/I individually. The primary outcome was all-cause hospital admission within 30 days post infusion.

Results
From February 1 to March 7, 2021, 358 patients received BAM and from March 17 to May 9, 2021, 86 and 179 patients received B/E and C/I, respectively. Compared to any combination infusion, patients who received BAM were significantly older, more likely to possess ≥ 2 qualifying EUA criteria, and less likely to be vaccinated for COVID-19 prior to infusion (Table 1). Following B/E and C/I, 4.5% of patients were admitted versus 10.1% for BAM, p=0.011. There were no significant differences in admission between B/E and C/I recipients, p=0.485. After excluding fully vaccinated patients (n=14) and adjusting for age and ≥ 2 EUA criteria, combination therapy remained associated with decreased odds of hospitalization compared to BAM (odds ratio, 0.48; 95% confidence interval, 0.24-0.94).

Conclusion
Combination therapy may be associated with fewer hospital admissions following infusion, although there were no statistically significant differences between the individual combination infusions. We suggest similar studies be conducted by other sites to understand the clinical impact of local SARS-CoV-2 variants on antibody efficacy.

Disclosures
Yi Guo, PharmD, BCIDP, Merck (Research Grant or Support) Kelsie Cowman, MPH, Merck (Research Grant or Support) Priya Nori, MD, Merck (Grant/Research Support) Priya Nori, MD, Nothing to disclose
525. Atovaquone for Treatment of COVID-19 (Ataq COVID-19) Trial
Authors: Jain Mamta K , Jain Mamta K , Sadek Hesham , de Lemos James , mcGuire Darren , Ayers Colby , Eiston Jennifer L , Lucas Claudia , Kamel Dena , Li Xilong , Agbor Barbine Agbor , Williams Noelle , Schoggins John 
Published: December 2021

Abstract

Background
Our group performed an in-silico screen to identify FDA approved drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication.

Methods
Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agreed to allow collection of saliva at baseline and twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted for viral load (VL) measurement by Real-time PCR. Our primary outcome was to examine the between group differences in log transformed VL(copies/mL) using generalized linear mixed-effect models of repeated measures from all samples. Additional analysis of Atovquone plasma concentrations were examined and correlated with viral load and body mass index (BMI).

Results
Of the 61 patients enrolled; 41 were received atovaquone and 19 placebo. Overall the population was predominately male Hispanic with a mean age of 51 years. The two groups were balanced (Table 1) with regard to age, gender, race, co-morbidities, days from onset of symptoms, baseline oxygen requirements, and receipt of COVID-19 specific standard of care treatment. A higher proportion with diabetes was noted in the Atovaquone arm. The log10 VL was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Although there was a decrease in VL over time, there was no differences between the atovaquone plus standard of care arm versus the standard of care arm (Figure 1). Additional analysis of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, inverse association between atovaquone levels and BMI (rho -0.44, p=0.03), and Day 5 concentrations and VL (rho -0.54, p=0.005).

Figure 1. Mean viral load of COVID-19 over time of atovaquone (blue) vs. placebo (red).
Table 1. Baseline characteristics

Conclusion
Although atovaquone showed promising in vitro antiviral properties for COVID-19, in this pilot study we did not detect a change in VL in patients who received atovaquone compared to placebo, possibly due to failure of patients achieve adequate drug levels.

Disclosures
Mamta K. Jain, MD, MPH, Gilead Sciences Inc. (Individual(s) Involved: Self): Research Grant or Support, Scientific Research Study Investigator; GlaxoSmithKline (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Vasgene (Individual(s) Involved: Self): Scientific Research Study Investigator
556. Ruxolitinib for the Management of Severe Pneumonia Caused by SARS-CoV-2. Exploring the Combination with dexamethasone
Authors: Molina Aaron , Olmedo-Reneaum Alejandro , Reyes-Paniagua Maria Del Rocio , Molina Mariana 
Published: December 2021

Abstract

Background
Mexico is one of the top five countries with a higher mortality rate of hospitalized patients of 30.1%. Since COVID-19 has been associated with immune dysregulation and hyper inflammation, JAK-12 inhibitors have been tested to reduce IL6 production. Studies have shown improvements when using ruxolitinib (rxb) in severely hospitalized patients with COVID-19. These have included patients in combination with corticosteroids such as dexamethasone (dxm). This work aims to test the response of hospitalized patients with severe or critical COVID-19 treated with rxb with or without dxm.

Methods
An experimental, open, prospective study in a single third-level hospital in Mexico was performed. The primary outcome was favorable clinical response defined as withdrawal or decline of supplementary oxygen. Secondary outcomes such as mean hospital stay, improvement in systemic inflammatory response parameters, and mortality were also evaluated. Statistical differences for baseline and final measure and the use and not use of dxm were estimated. The study included adults with SARS-CoV-2 infection confirmed with polymerase chain reaction, radiological pneumonia, and oxygen saturation less than 90%. Rxb was administered 5mg/12hrs/15days, IV dxm 6mg/day/10days.

Results
The final sample was 108 adults with complete information and informed consent. Sixty-two patients (57%) received only rxb. There were no differences between groups for any parameter at the beginning of treatment, and all patients were receiving supplemental oxygen. After 28-day follow-up, 70% reduce supplemental oxygen requirement (74% rxb and 71% rxb+dxm; p=0.628), 18% remained, and 2% increases support (1% with rxb, and 5% rxb+dxm; p&lt; 0.001); 87% of patients were discharged (89% rxb and 85% rxb+dxm; p=0.603). In both groups, there was a significant reduction of CRP, LDH, and Ferritin on day 15. The mortality rate was 9% (no difference in groups; p=0.453), and a higher proportion died for Pseudomonas aeruginosa superinfection in the rxb+dxm group (p&lt; 0.001).
Differences for support oxygen at baseline and discharge

Final health outcomes of patients with severe or critical COVID-19 in a third-level hospital in Mexico

Conclusion
The use of rxb could be considered as a treatment helping clinical improvement in hospitalized patients with severe COVID-19. Combination with dxm apparently did not add clinical benefits. It should be further evaluated.

Disclosures
All Authors: No reported disclosures
557. Trends in Remdesivir Treatment Over the Course of the COVID-19 Pandemic
Authors: Xin Liao J , Lopes Vrishali , Caffrey Aisling 
Published: December 2021

Abstract

Background
Remdesivir is approved for use in the United States for treatment of COVID-19 requiring hospitalization. Real-world data on trends in remdesivir use may elucidate its benefits and place in therapy.

Methods
Hospitalized Veterans with a positive SARS-CoV-2 polymerase chain reaction (PCR) test that were treated with remdesivir at a Veterans Affairs Medical Center from May 2020 to April 2021 were included. Monthly trends in remdesivir treatment, as well as patient characteristics and clinical outcomes among patients treated with remdesivir, were assessed with joinpoint regression to calculate average monthly percent change and corresponding 95% confidence intervals (CI).

Results
A total of 30,333 Veterans were hospitalized with a positive PCR test over the study period, and 13,639 were treated with remdesivir (45%). Throughout the study period, the proportion of Veterans treated with remdesivir increased significantly (4.5% per month, 95% CI 0.5%-8.6%) and median time to remdesivir initiation decreased significantly (12% per month, 95% CI -15.8% to -8.0%). Though demographic characteristics of Veterans treated with remdesivir remained stable, including age, race, and obesity, improvement in clinical outcomes were observed, including median length of hospital stay which decreased by 6.5% per month (95% CI -9.1% to -3.8%), intensive care admissions which decreased by 4.6% per month (95% CI -6.3% to -2.8%) and inpatient mortality which decreased by 6.3% per month (95% CI -9.4% to -3.1%). By April 2021, most patients initiated remdesivir on the day of admission, and the inpatient mortality rate decreased to 7.9% from 19.2% in May 2020.

Conclusion
Over the course of the COVID-19 pandemic, utilization of remdesivir increased while initiation of remdesivir occurred earlier in the hospital admission, with concurrent reductions in length of hospital stay, intensive care admissions, and inpatient mortality.

Disclosures
Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi, Inc (Research Grant or Support)
559. A Nationwide Survey of COVID-19 Management in the Dominican Republic Over the Course of the Pandemic
Authors: Mena Lora Alfredo J , Rojas-Fermin Rita Alexandra , de Luna David , Echeverria Stephanie L , Roque Yori , Calcano Ruben , Blanco Claudia , Perez Clevy , Hernandez Anny , Espinal Adames , Coronado Carolina , Castro Michelle , Batista Arelis , Borgetti Scott , Bleasdale Susan C 
Published: December 2021

Abstract

Background
COVID-19 was declared a global Public Health Emergency by the WHO in January 2020. Limited treatment options existed early in the pandemic. As COVID-19 spread across the globe and new therapeutics emerged, different interpretations of the literature grew, and major societies relayed conflictive recommendations. There is a paucity of data on COVID-19 management in low- and middle-income countries. As a result, we performed a nationwide survey of local treatment practices in the Dominican Republic (DR).

Methods
We performed an anonymous survey of infectious diseases specialists in the DR and US. The survey collected hospital characteristics and COVID-19 management protocols during different quarters of 2020-21. Management was categorized by drug and disease severity based on supplemental oxygen requirements. A convenience sample in the US representing community and academic sites was surveyed for point comparison between the US and DR.

Results
The survey was completed by physicians from a total of 11 sites located in 4 cities of the DR: Santo Domingo (3), Santiago (4), La Vega (2) and San Francisco (2). These cities were representative of all regions in the country. The survey included 7 (64%) hospitals with &lt; 200 beds, 3 (27%) with 201-300 beds, and 1 (9%) with &gt;400 beds. Seven (47%) were private, 2 (13%) public, and 6 (40%) were teaching hospitals. In the US, 2 academic hospitals with &gt;400 beds and 2 community hospitals with &lt; 200 beds in a major city were surveyed. Management of COVID-19 at sites in the DR and US throughout the pandemic is plotted in Figure 1. Remdesivir use by disease severity is plotted in Figure 2.
Figure 1. Management of COVID-19 at sites in the US and DR throughout the COVID-19 pandemic

FIgure 2. Remdesivir use by disease severity at sites in the US and DR throughout the COVID-19 pandemic

Conclusion
Throughout the pandemic, as therapeutic options evolved, hospitals and physicians had to adapt to changing guidelines and availability of novel drugs. Variability between countries and sites emerged. The use of hydroxychloroquine and convalescent plasma waned more rapidly in the US. Dexamethasone was widely used at all sites. Tocilizumab and remdesivir were used more liberally in the DR. Antimicrobial stewardship limited these agents at US sites to more narrow therapeutic windows which could explain the discrepancies seen between the US and DR. Uncertainty of benefit in certain disease states, limited availability, and cost may also play a role.

Disclosures
All Authors: No reported disclosures
565. Risk of COVID-19 Among Healthcare Workers After Launch of Vaccination Campaign at an Academic Medical Center
Authors: Navalkele Bhagyashri D , Lucar Jose , Brock James B , Parham Jason 
Published: December 2021

Abstract

Background
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus affected healthcare workers (HCWs) adding additional burden on staffing shortages. COVID-19 vaccination (mRNA 1273 and BNT162b2) has been shown to protect against severe disease, death and reduced risk of asymptomatic infection and transmission from fully vaccinated individuals. Here, we present the impact of COVID-19 vaccination (CoVac) on risk of developing COVID-19 based on test results among unvaccinated and vaccinated HCWs.

Methods
Our academic medical center with 11,785 HCWs on its Jackson campus initiated non-mandatory CoVac among HCWs with BNT162b2 on December 16, 2020. Individuals ≥ 2 weeks after 1st dose of vaccine were defined as partially vaccinated and those ≥2 weeks from 2nd dose of vaccine were defined as fully vaccinated. Per facility policy, all symptomatic HCWs (irrespective of vaccination status) were recommended to undergo SARS-CoV-2 RT-PCR testing. Asymptomatic HCWs were also tested upon household exposure, however, this policy was changed on March 9th 2021 to allow fully vaccinated asymptomatic HCWs to work without need for quarantine or testing. Universal masking policy among HCWs remained effective at our center during study period.

Results
Between the launch of COVID-19 vaccination on December 16, 2020 and April 30, 2021, 5,855 HCWs received one dose of vaccine, and 5,687 received both doses. A total of 1,329 unique HCWs underwent COVID-19 testing between January 4, 2021 and April 30, 2021. Of those, 217 (16.3%) tested positive for SARS-CoV-2 infection; 204 were unvaccinated, 7 were partially vaccinated, and 6 were fully vaccinated (figure 1). Of the 6 fully vaccinated employees, 1 was asymptomatic (testing for travel purposes), 4 had mild symptoms, and one elderly employee required hospitalization with oxygen supplementation and had a complete recovery. No facility outbreaks were reported related to asymptomatic, work exposed, fully vaccinated HCWs.

Unvaccinated healthcare workers were more likely to test positive for SARS-CoV-2 compared to partially and fully vaccinated healthcare workers.

Conclusion
COVID-19 vaccination protected HCWs by reducing risk for developing COVID-19. Vaccinating healthcare workers is a crucial infection prevention measure to reduce disease burden, avoid staffing shortages and create a safe environment in the healthcare facility to prevent transmission to other staff and at-risk patients.

Disclosures
All Authors: No reported disclosures