bluuebunny/crossref_metadata_2025_split huggingface dataset:
558. Implementation and Outcomes of a COVID-19 Monoclonal Antibody Treatment Program in an Urban Safety-net Community Hospital
Authors: Mena Lora Alfredo J , Echeverria Stephanie L , Herald Fischer , McSweeney James , Gumasana Harshil , Burgos Rodrigo M , Borgetti Scott 
Published: December 2021

Abstract

Background
Neutralizing monoclonal antibodies (mAbs) bind to the receptor binding domain of the spike protein of SARS-CoV-2. In November 2020, several mAbs were issued an EUA by the FDA as single-dose intravenous (IV) infusions for treatment of mild to moderate COVID-19. mABs were allocated to local health facilities capable of administering infusions and managing side effects. Creating an outpatient infusion program during the COVID-19 winter surge can be logistically difficult. Our goal was to implement a mAb outpatient infusion program at an urban safety-net community hospital designed to serve communities most heavily impacted by COVID-19.

Methods
The emergency department (ED) fast-track was repurposed for the mAb program with protocols from the infectious diseases physician and antimicrobial stewardship. Education materials with indications for mAbs were distributed in surrounding clinics serving our community. The program was available to all patients meeting criteria outlined in the protocol, 24/7, including but not limited to current ED patients and referrals from facilities in the vicinity.

Results
Between December 1, 2020 and March 1, 2021, a total of 37 patients were treated: 51% male, 57% Hispanic or Latinx, 27% Black, and 95% (35) represented ZIP codes with high COVID-19 burden (Figure 1). Bamlanivimab was used for each instance and all infusions met criteria. Patient indications for mAb infusion are listed in Figure 2. Parenteral antibiotics were given to 10.8% and 35% received oral antibiotics upon discharge. At 30 days post-infusion, 8% (3) required hospitalization and there were no deaths.

Zip codes with high COVID-19 disease burden served by our mAB infusion program

Distribution of patients who received mAB infusions by indication

Conclusion
A mAb outpatient infusion program was successfully deployed in a safety-net community hospital. We believe strengths of the program included the flexible infusion hours and convenient referral site for patients and providers. Of importance, this program was able to provide services to minorities from ZIP codes most heavily impacted by COVID-19. Unfortunately, antibacterial use was common and may reflect broader unnecessary use in COVID-19 patients. Whilst mAb treatment was deemed appropriate in all instances via protocol inclusion criteria, antibacterial stewardship programs may need to expand to ED settings for COVID-19 management.

Disclosures
All Authors: No reported disclosures
560. Evaluation of Optimal Methylprednisolone Dose in Patients with Covid 19
Authors: Ferreiro Jose Luis Lamas , Otero Judith Álvarez , Piñeiro Fernando Maroto , Ortega Iolanda Abalde , Villar Marta Rodríguez , Losada Sonia Morón , González Irea Vidal , Rico Alejandra Canoa , González Laura Fernández , Fernández Emilia Fernández , Vila Marta Costas , Rivo Ana Sanjurjo , Fernández Francisco Fernández , Paz Ferrín Jose Manuel , Blanco Alexandra Arca , Alonso María , De la Fuente Javier 
Published: December 2021

Abstract

Background
Optimal dose of methylprednisolone in patients with moderate or severe COVID-19 is unclear. In our hospital, the use of 250-500 mg/day of methylprednisolone was frequent in the first wave of the pandemic. Lower dose were recommended in our protocol since September 2020. The aim was to evaluate the impact of methylprednisolone dose in the outcome of patients with moderate or severe COVID-19.

Methods
This is a retrospective and observational study. Inclusion criteria: SARS-CoV-2 infection diagnosed by PCR, admission to our hospital between March 2020 and February 2021, SatO2 &lt; 94% or SatO2/FiO2 &lt; 447. Two treatment groups were compared: patients treated with 0.5-1.5 mg/kg/day (group 1) and patients treated with more than 1.5 mg/kg/day (group 2). The primary outcome analyzed was orotracheal intubation (OTI) or death from any cause at 28 days after admission. Differences in demographic, clinical and laboratory characteristics between treatment groups were analyzed. Variables with P &lt; 0.1 were included in a binary logistic regression model, calculating a propensity score for assigning each patient to group 1 treatment. Bivariate analysis was performed to identify variables associated with worst outcome. Finally, Cox regression was performed including treatment group, propensity score as covariate and all the variables with P&lt; 0.05 in the bivariate analysis.

Results
285 patients were included, 197 in group 1 and 88 in group 2. The median age was 73 years, 52,3% were male. Mortality or OTI at 28 days was 24,9%. There was a higher proportion of patients in group 1 with COPD (9,6% vs 1.1%, P&lt; 0.01), dyspnea (60.4% vs 45.5%, P=0.01), sepsis (22.8% vs 13.6%, P=0.07). Patients in group 2 had more impaired consciousness (18.2% vs 8.6%, P=0.02). The median of lymphocytes count was lower in group 1 (900 vs 1025, P=0.01). There were no differences in the primary outcome between treatment groups (26.1% in the group 2 vs 24.4% in the group 1, P=0.7).

Conclusion
The use of high dose of methylprednisolone compared with intermediate dose is not associated with a better outcome in patients with moderate or severe COVID-19.

Disclosures
All Authors: No reported disclosures
561. Phase 3 Trial of Fostamatinib for the Treatment of COVID-19: Repurposing an Immunomodulatory Drug Previously Approved for Immune Thrombocytopenia
Authors: Mallat Ziad , Lobo Suzana Margareth , Malik Anuj , Tong Sandra 
Published: December 2021

Abstract

Background
Key pathologies in severe COVID-19 include immune cell activation, inflammatory cytokine release, and neutrophil extracellular trap release (NETosis), which are mediated by spleen tyrosine kinase (SYK) (Figure 1). Fostamatinib, an oral SYK inhibitor approved for chronic immune thrombocytopenia, has shown activity in vitro using plasma from patients with severe COVID-19, by abrogating the hyperimmune response triggered by anti-spike IgG; 1 inhibiting hyperactivation in platelets; 2 and blocking NETosis in neutrophils.3 R406, active metabolite of fostamatinib, protected against LPS-induced acute lung injury and thrombosis in mice.4,5 In clinical studies, fostamatinib reduced IL-6 in patients with rheumatoid arthritis.6 Therefore, a phase 2 study (NCT04579393) evaluated fostamatinib vs. placebo plus standard of care (SOC) in 59 hospitalized COVID-19 patients (manuscript pending). We initiated a phase 3 clinical study (NCT04629703) of fostamatinib for the treatment of COVID-19.

Methods
A double-blind, randomized, placebo-controlled, adaptive design, multi-center, Phase 3 study (NCT04629703) is underway to evaluate the safety and efficacy of fostamatinib in 308 adult patients with COVID-19 (Figure 2). Hospitalized patients without respiratory failure (with or without supplemental oxygen) were included. Patients with ARDS or using extracorporeal membrane oxygenation (ECMO) were excluded. Patients will receive fostamatinib 150 mg BID or placebo for 14 days; both arms receive SOC. The primary outcome will be progression to severe/critical disease (worsening in clinical status score on the 8-point ordinal scale) within 29 days of the first dose of study drug. Fostamatinib is investigational for COVID-19.

Results
Blinded update of trial in progress as of 28 April 2021. 12 patients have been randomized in North and South America. The clinical status score at Baseline was 5 (Hospitalized, requiring supplemental oxygen) in all 12 patients. Five patients had 8 adverse events (AE) (Fig 3). One AE (PE) was serious and is resolving. No deaths have been reported. At least two patients have been discharged (Day 5, Day 13) with continued dosing at home.

Conclusion
Fostamatinib has the potential to provide a treatment option for the hyperimmune complications of COVID-19.

Disclosures
Ziad Mallat, MD, PhD, Rigel Pharmaceuticals, Inc. (Consultant) Sandra Tong, MD, Rigel Pharmaceuticals, Inc. (Employee, Shareholder)
563. Experience of a Private Hospital in the Treatment of COVID-19 Pneumonia in Veracruz, Mexico
Authors: Del Carpio-Orantes Luis , Márquez-Rodriguez Luis Alberto , García-Pérez José Luis , Rodríguez-Santos Christian Alberto , Llaven-Velázquez Carlos Yahir , Gutiérrez-Martínez Eduardo , Lucho-Morales Anel Concepción , Mendoza-Hernández Juan Carlos , García-Ortíz Jorge José , Medrano-Rios Luis Jaime , Ruiz-Castro Enrique , Ortiz-Hernández Manuel Alejandro 
Published: December 2021

Abstract

Background
Large mortality rates have been reported in the Mexican public health system, however in the experiences of private hospitals that have resources and infrastructure this is lower compared to the national average.

Methods
Descriptive and retrospective study. Adult patients treated for pneumonia due COVID-19 from April to December 2020 are entered into the study. Its general characteristics such as gender and age, comorbidities, influenza vaccination history, clinical characterization, laboratory and tomographic diagnosis of sars cov2 pneumonia are studied, as well as the drug and oxygen therapy treatments received and finally, its evolution and clinical outcome.

Results
132 patients were studied, of which 51% were female. The main age groups affected were 65 and over (43.9%), 50-59 years (20.4%) and 25-44 years (16.6%). The main comorbidities found were: arterial hypertension (43.9%), Diabetes mellitus 2 (33.3%), heart disease (11.3%) and obesity (10.6%). 95.4% of the patients were not vaccinated against influenza. The main symptoms reported were: fever (92%), cough (87%), dyspnea (76%) and headache (52%). The diagnosis was confirmed with RT-PCR in 63%, reporting negative RT-PCR in 36%; the antigen test was positive in 1%. Regarding the findings of the chest computed tomography, CORADS 5 was reported in 30%, CORADS 6 in 3% and CORADS 4 in 20%. The main treatments used in patients with severe inflammatory pneumonia were: steroids (98%), enoxaparin (100%), tocilizumab (20%), baricitinib (60%), direct oral anticoagulants (10%), fibroquel (5%). 60% were treated with a combination of two or more drugs. The main oxygenation contributions were: 20% nasal tips - mask/reservoir, 60% high flow nasal cannula, 20% mechanical ventilation. In 95% the prone position was indicated. Regarding the clinical evolution, 65.1% were towards improvement, 17.4% died, 12.1% requested transfer to another unit and 5.3% requested voluntary discharge. Overall mortality was 17%.
Medications in ICU

Ventilation strategies

Conclusion
A hospital strategy that has the necessary resources and infrastructure as well as openness to the use of medication with emergency approvals for its use or off-label indications, can help limit morbidity and mortality in vulnerable populations and manifest risk factors such as Mexican population

Disclosures
All Authors: No reported disclosures
564. SARS-CoV-2 Ferritin Nanoparticle Vaccines Elicit Broad SARS Coronavirus Immunogenicity
Authors: Joyce M G , Chen Wei-Hung , Sankhala Rajeshwer , Hajduczki Agnes , Thomas Paul , Martinez Elizabeth , Peterson Caroline , Rao Mangala , Modjarrad Kayvon 
Published: December 2021

Abstract

Background
The zoonotic emergence of SARS-CoV-2 quickly developed into a global pandemic. Multiple vaccine platforms have been advanced to clinical trials and emergency use authorization. The recent emergence of SARS-CoV-2 virus variants with Spike receptor-binding domain (RBD) and N-terminal domain (NTD) mutations, highlights the need for next-generation vaccines that can elicit immune responses that are resilient against Spike mutations.

Methods
Using a structure-based vaccine design approach, we developed multiple optimized SARS-CoV-2 nanoparticle immunogens that recapitulate the structural and antigenic profile of the SARS-CoV-2 prefusion spike. We assessed these immunogens in murine immunogenicity studies and in a K18-hACE2 transgenic mouse model with a SARS-CoV-2 challenge. Immune sera from vaccinated mice were assessed for SARS-CoV-2 binding, and neutralization against SARS-CoV-2, variants of concern, and the heterologous SARS-CoV-1 virus.

Results
In combination with a liposomal-saponin based adjuvant (ALFQ), these immunogens induced robust binding, ACE2-inhibition, and authentic virus and pseudovirus neutralization. A Spike-Ferritin nanoparticle (SpFN) vaccine elicited neutralizing ID50 titers &gt;10,000 after a single immunization, while RBD-Ferritin (RFN) nanoparticle immunogens elicited ID50 titer values &gt;10,000 values after two immunizations. Purified antibody from SpFN- or RFN-immunized mice was transfused into K18-ACE2 transgenic mice and challenged with a high-dose SARS-CoV-2 virus stock. In order to understand the breadth of vaccine-elicited antibody responses, we analyzed SpFN- and RBD-FN-immunized animal sera against a set of heterologous SARS-CoV-2 RBD variants and SARS-CoV RBD. High binding titers with ACE2-blocking activity were observed against SARS-CoV-2 variants and the heterologous SARS-CoV-1 RBD. Furthermore, both SpFN- and RFN-immunized animal sera showed SARS-CoV-1 neutralizing ID50 titers of &gt;2000.

Conclusion
These observations highlight the importance of SARS-CoV-2 neutralizing antibody levels in providing protection against emerging SARS-like coronaviruses and provide a robust platform for pandemic preparedness.
Structure-based design enables development of a SARS-CoV-2 nanoparticle immunogen.

Disclosures
All Authors: No reported disclosures
569. Characterization of COVID-19 Vaccine Breakthrough Infections in Metropolitan Detroit
Authors: sturla Nicholas , Kassab Rita , Khansa Rafa , Chevalier Thomas , Allard David , Tibbetts Robert , Samuel Linoj , Suleyman Geehan 
Published: December 2021

Abstract

Background
Although COVID-19 vaccines are very effective, vaccine breakthrough infections have been reported, albeit rarely. When they do occur, people generally have milder COVID-19 illness compared to unvaccinated people. A total of 10,262 (0.01%) SARS-CoV-2 vaccine breakthrough infections had been reported as of April 30, 2021. The objective of this study was to evaluate the effectiveness of COVID-19 vaccines and characterize breakthrough infections in our patient population.

Methods
This was a retrospective review of all consecutive COVID-19 vaccine breakthrough infections at Henry Ford Health System (HFHS) in metropolitan Detroit, Michigan, from December 17, 2020 to June 7, 2021. Centers for Disease Control (CDC)'s breakthrough infection definition (detection of SARS-CoV-2 RNA or antigen in a respiratory sample ≥14 days after completion all recommended doses of COVID-19 vaccine) was used to identify cases. Vaccination status was extracted from the electronic medical records using Epic™ SlicerDicer.

Results
A total of 228,674 patients, including healthcare workers (HCW), were fully vaccinated in our healthcare system. We evaluate 299 patients for breakthrough infection but only 179 (0.08%) patients met the definition; 108 (60%) were female with median age of 59, 60 (33%) were HCW, and 11 (6%) were immunocompromised. The majority (92%) were asymptomatic (62 or 35%) or had mild/moderate illness (102 or 57%); 14 (8%) had severe or critical illness. The status of one patient was unknown. Of those who were symptomatic, 24 (13%) required hospitalization, and 3 (2%) required intensive unit care. One patient admitted for heart failure exacerbation died unexpectedly prior to being discharged. Nine had previous COVID-19 within 4 months but only one was symptomatic; this likely represented residual shedding in the asymptomatic patients.

Conclusion
COVID-19 vaccine was very effective among our patients and breakthrough infections were rare. Moreover, the vaccine reduced disease severity and mortality. Efforts should aim to increase vaccine uptake.

Disclosures
All Authors: No reported disclosures
570. Prioritized Access to COVID-19 Vaccines Among Vulnerable Communities Increases Vaccination Rates
Authors: Fernandez Leonor , O'Donoghue Ashley , Shorett Peter , Blair Jonathan , Markson Lawrence , Dechen Tenzin , Stevens Jennifer , Wright Sharon 
Published: December 2021

Abstract

Background
Based on national recommendations,1 Beth Israel Lahey Health (BILH) in Eastern Massachusetts (MA) prioritized vulnerable communities in our distribution of COVID-19 vaccines. We hypothesized that creating prioritized access to appointments for patients in these communities would increase the likelihood vaccination.

Methods
The BILH health system sent vaccine invitations first to patients of two clinics in vulnerable neighborhoods in Boston (Wave 1), followed by other patients from vulnerable communities (Wave 2) up to 1 day later, and then by all other patients (Wave 3) after up to 1 more day later. To identify whether early access/prioritization increased the likelihood of receipt of vaccine at any site or a vaccine at a BILH clinic, we compared patients in Wave 1 in a single community with high cumulative incidence of COVID-19 (Dorchester) to patients in Wave 2 during a period of limited vaccine access, 1/27/21-2/24/21. Each wave was modeled using logistic regression, adjusted for language and race. By taking the difference between these two differences, we are left with the impact of early vaccination invitation in Wave 1 for a subset of our most vulnerable patients (termed difference-in-differences; Stata SE 16.0).

Results
In our study of Waves 1 and 2, we offered vaccinations to 24,410 patients. Of those, 6,712 (27.5%) scheduled the vaccine at BILH (Table 1). Patients in Wave 1 were much more likely to be vaccinated at BILH than patients in Wave 2. Patients offered the vaccine in Wave 1 and living in Dorchester were 1.7 percentage points more likely to be vaccinated at all (p=0.445) and 9.4 percentage points more likely to be vaccinated at BILH than another site in MA (p-value = 0.001), relative to patients living outside of Dorchester and offered the vaccine in Wave 2 (Table 2).

The coefficient of interest is on Wave1*Dorchester, 0.094. This indicates that residents of Dorchester who were offered the vaccine in Wave 1 were 9.4 percentage points more likely to receive the vaccine at BILH, given that they were vaccinated, relative to patients living outside of Dorchester and offered the vaccine in Wave 2.

Conclusion
Patients residing in an urban community given prioritized access to vaccination had a higher likelihood of vaccination at our health system, given that they were vaccinated, than patients in other urban communities without prioritized access. We provide an example of a successful effort to move towards equity in access to COVID-19- vaccines, in contrast to larger national trends.2,3 Health systems can use a prioritization approach to improve vaccination equity.

Disclosures
All Authors: No reported disclosures
572. Real-world Effectiveness of COVID-19 mRNA Vaccines against Hospitalizations and Deaths in a Retrospective Cohort
Authors: Vahidy Farhaan S , Pischel Lauren , Tano Mauricio E , Pan Alan , Boom Marc L , Sostman Henry , Nasir Khurram , Omer Saad 
Published: December 2021

Abstract

Background
The effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 vaccines after two doses needs to be demonstrated beyond clinical trials.

Methods
In a retrospective cohort assembled from a cross-institution comprehensive data repository, established patients of the health care system were categorized as having received no doses, one dose or two doses of SARS-CoV-2 mRNA vaccine through April 4, 2021. Outcomes were COVID-19 related hospitalization and death.

Results
Of 94,018 patients 27.7% had completed two doses and 3.1% had completed one dose of a COVID-19 mRNA vaccine. The two dose group was older with more comorbidities. 1.0% of the two dose group had a COVID-19 hospitalization, compared to 4.0% and 2.7% in the one dose and no dose groups respectively. The adjusted Cox proportional-hazards model based vaccine effectiveness after two doses (vs. no dose) was 96%(95% confidence interval(CI):95–97), compared to 78%(95%CI:76–82) after one dose. After two doses, vaccine effectiveness for COVID-19 mortality was 97.9%(95%CI:91.7–99.5), and 53.5%(95%CI:0.28–80.8) after one dose. Vaccine effectiveness at preventing hospitalization was conserved across age, race, ethnicity, Area Deprivation Index and Charlson Comorbidity Indices.
Cohort Enrollment and Distribution by Immunization Status and Vaccine effectiveness against mortality

Cohort members are described by their immunization status and hospitalization at the end of the study period ending April 4th, 2021. Percentages compare this population to the total established patients. Each group is then divided into when hospitalized events occurred across immunization status. These percentages compare the number of events to the population in the immunization status at the end of the analysis period. Odds ratios for mortality were calculated and vaccine effectiveness calculated as 1 minus odds ratio times 100%.

Conclusion
In a large, diverse US cohort, receipt of two doses of an mRNA vaccine was highly effective in the real-world at preventing COVID-19 related hospitalizations and deaths with a substantive difference in effectiveness between one and two doses.

Disclosures
All Authors: No reported disclosures
573. Digital Patient/Caregiver Education: A Tool to Improve COVID-19 Vaccination Rates and Confidence Among the Public
Authors: Larkin Amy , Armagan Allison 
Published: December 2021

Abstract

Background
Due to patient hesitancy surrounding the COVID-19 vaccination initiative, the public needs accurate and timely education that encourages partnership with medical professionals.

Methods
This study assessed the impact of online patient/caregiver education on knowledge, confidence and intent to act. The educational intervention consisted of 4 activities published on a dedicated COVID-19 learning center on WebMD Education portal from April-May, 2021. The activities were comprised of text and integrated visuals, with 3 of the activities being further customized with a patient or healthcare professional (HCP) video commentary. Demographic questions were asked prior to each activity. Knowledge questions were asked both before and after to assess learning gains. Intent to change and confidence questions were asked at the end of each activity. Absolute improvements were calculated for pre/post questions. An initial data pull was conducted on 6/7/2021 for the purpose of this abstract, and data for the complete analysis will be collected until approximately 8/7/21.

Results
To date, 14,911 learners (3,579) of which responded to the pre/post questions) have participated in the activities, and have demonstrated improvements in knowledge and high levels of confidence and intent to act (Figure). Activity 1: COVID-19 Vaccines: Covering the Basics. Demographics (n=155): 50% male; 41% White, non-Hispanic, 30% Asian; 52% over the age of 54. Activity 2: Understanding the Why, Who, and When of COVID-19 Vaccines. Demographics (n=2,325): 66% female; 51% White, non-Hispanic, 18% Asian; 54% over the age of 54. Activity 3: What to Expect When You Get the COVID-19 Vaccine. Demographics (n=500): 66% female; 49% White, non-Hispanic, 22% Asian; 56% over the age of 54. Activity 4: What Have You Heard about Herd Immunity and COVID-19. Demographics (n=599): 63% female; 53% White, non-Hispanic, 25% Asian; 53% over the age of 54.

Conclusion
The metrics and outcomes gathered in this assessment are a strong indicator that online patient/caregiver activities on WebMD Education improved knowledge and confidence and prompted intent to act related to COVID-19 vaccines. These findings highlight the potential for well-designed online education to overcome vaccine related challenges of the COVID-19 pandemic.

Disclosures
All Authors: No reported disclosures