bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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 >10,000 after a single immunization, while RBD-Ferritin (RFN) nanoparticle immunogens elicited ID50 titer values >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 >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

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

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

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

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
574. High Acceptance and Rapid Implementation of COVID-19 Vaccine in a Public HIV Clinic in Northern California: An Initial Analysis of Social Determinants
Authors: Lin Jennifer , Wong Frank Oi-Shan , Thibodeaux Christopher , Choi-McInturff Moon , Tamayo Aracely , Levy Vivian
Published: December 2021

Background

Safety net HIV providers face operational challenges during the COVID pandemic with services often transformed to telehealth. HIV infected persons are a priority population for SARS CoV-2 vaccination. Medical mistrust of COVID vaccines has been cited as a contributor to vaccine hesitancy. Data on efficient and successful vaccination efforts of HIV infected persons in safety net health systems is needed. In San Mateo County, Latino persons comprised 42% of all COVID cases, Whites 16%, and African Americans 2%.

Methods

SARS CoV2 vaccination with BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna) or Ad26.COV2.S (Janssen) vaccine were offered beginning February 2, 2021 through May 28, 2021 in a northern California public County HIV clinic. Clinic patients were contacted by bilingual English/Spanish speaking HIV clinic staff and appointments scheduled at County affiliated vaccination sites. Clinic staff followed up by phone with patients who did not initially accept vaccine. We calculate the percentage of patients who completed vaccine series and use multivariable logistic regression analysis to estimate the odds of series completion by patient race/ethnicity, gender and age.

Results

Virtually all, 95% (349/365) of HIV patients in our County HIV clinic were offered vaccine during a 17 week period. Among those, 86% (313/365) accepted and received at least one dose and 80% completed the series (292/365) at time of this analysis. Janssen vaccine was given to only 2% (7/313) patients. Series completion was highest among Latinos and Asians. Latinos had the highest odds of vaccine series completion (OR = 4.12; 95% CI 1.71 - 9.93).

COVID-19 Vaccine Series Completion in a California Public HIV Clinic by Race/Ethnicity, Age and Sexual Orientation, n=364

Conclusion

HIV patients offered SARS CoV2 vaccine by County HIV clinic staff with established patient care relationships had high vaccine acceptance (80%), comparable to 68% series completion in the county overall and 56% in the health equity quartile county census tracts. Latino HIV infected persons were most likely to complete the COVID vaccine series. Ryan White funded HIV clinics are ideal hubs to coordinate HIV patient COVID vaccination efforts. Adding COVID vaccine completion to HIV clinic performance measures would likely be beneficial.

Disclosures

All Authors: No reported disclosures
575. Local Experience of Breakthrough SARS-CoV-2 Infections After Full Vaccination
Authors: Khan Ahmed A , Havener Gayla , Graham Donald , Miller Brian , O'Neill Gail , Sundareshan Vidya
Published: December 2021

Background

SARS-CoV-2 the etiology of COVID-19 has caused more than 33 million cases and almost 600,000 deaths in the United States alone. Vaccination is a vital tool in controlling the pandemic. With accelerated infection rates in various parts of the world, the incidence of variants has risen and threatens to set back the long sought after immunity, provided by available vaccines. The objective of this study was to evaluate the breakthrough infection rate after complete vaccination, in Sangamon County, with a rural and urban population of 195,000 in Central Illinois.

Methods

Data regarding breakthrough infections collected from the Sangamon County Department of Public Health, included the total number of infections, time after vaccination, age range of those infected and the type of vaccine used. Complete vaccination was defined as 14 days after the single dose of Johnson & Johnson/Janssen or the second dose of Pfizer-BioNTech or Moderna Inc. vaccine.

Results

The number of fully vaccinated individuals at the time of writing of this study was 87,086 which corresponded to 44.58 % of the total population. The breakthrough infection percentage was calculated as 0.036%. The mean time after vaccination to infection was 49.13 days with a standard deviation of 23.28.

Conclusion

Breakthrough infections among fully vaccinated individuals in our county, have been quite rare, which points to the high efficacy of the vaccines. A complex number of factors likely contribute to this including virus-related factors i.e. variant forms and specific patient-related factors which are not a part of this study. The afore-mentioned high efficacy rate of the vaccines provides further justification, to continue to pursue a persistent vaccination strategy to mitigate the effects of the SARS-CoV-2 virus.

Disclosures

All Authors: No reported disclosures
576. Determinants of COVID-19 Vaccine Hesitancy: A Cross-Sectional Study in 3 Communities in the United States and Lebanon
Authors: Yasmin Mohamad , Tfaily Mohamad Ali , Emery Rebecca P , Hassouna Habiba , Obeid Rita , Bhugra Mudita , Bonomo Robert A , Kanafani Zeina
Published: December 2021

Background

The ongoing COVID-19 pandemic has thus far resulted in substantial worldwide mortality. As of November 2020, COVID-19 vaccines became available following Emergency Use Authorization (EUA) issued by the FDA. Recent longitudinal studies published as of March 2021 demonstrated that vaccine hesitancy remains high despite improvements compared to 2020. This study sought to explore the perceptions, beliefs, attitudes, and knowledge surrounding COVID-19 and identify determinants uniquely associated with vaccine hesitancy.

Methods

A cross-sectional electronic survey was created based on CDC & IDSA recommendations. The survey was distributed from March 2021 until June 2021 randomly to faculty members, healthcare workers, and students (≥18 years old) across 3 major academic centers (Case Western Reserve University, Spectrum Health, and the American University of Beirut Medical Center [AUBMC]). Data collected included socio-economic characteristics, demographics, knowledge, and attitudes pertaining to COVID-19 and vaccination. A multivariable regression model was utilized to evaluate for independent associations between variables and vaccination willingness/hesitancy as the primary outcome.

Results

In total, 7,197 participants completed the survey with an overall response rate of 94%. Females constituted 75.7% of the study population. Overall, 87.8% of the study cohort indicated willingness to get vaccinated. Factors associated independently with vaccination hesitancy included: younger age, lower attained education, lower knowledge score, physician recommendation against vaccination, not receiving the influenza vaccine annually, and other beliefs and attitudes as reported in table 1.

Table 1. Independent predictors of COVID-19 vaccine hesitancy among study respondents

Conclusion

Most survey respondents indicated willingness to receive COVID-19 vaccination. The perception or belief that vaccination is more harmful than COVID-19 disease represented an especially robust barrier against vaccination. Since recommendations made by healthcare providers were strongly associated with either vaccination hesitancy or willingness to get vaccinated, developing educational strategies at this level could enhance vaccine acceptance in an effort to curb the pandemic.

Disclosures

Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)
582. Risk Factors for Progression to Hospitalization in Adolescents Presenting with Mild or Moderate COVID-19
Authors: Dubois Melanie , Campbell Jeffrey , Lamb Gabriella S , Lamb Gabriella S , Nakamura Mari M
Published: December 2021

Background

Most adolescents (age 12-17 years) with COVID-19 have mild disease. However, certain comorbidities may be risk factors for disease progression, and hospitalization rates for this age group have increased. Adolescents and adults with mild to moderate COVID-19 are eligible for monoclonal antibody therapy. To identify subgroups likely to benefit from this intervention, we evaluated the relationship between comorbidities and need for hospitalization in US adolescents presenting with mild to moderate COVID-19.

Methods

We analyzed presence of comorbidities and need for hospitalization within 28 days of diagnosis for adolescents in the PIDTRAN registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes (DM), immunosuppressive disease or treatment (IS), sickle cell disease (SCD), congenital/acquired heart disease (CHD), neurologic disease/neurodevelopmental disorders (ND), medical-related technology dependence (MTD), and pulmonary disease requiring daily inhaled corticosteroids (PD). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization.

Results

1574 patients met inclusion criteria, of whom 180 (11.4%) were hospitalized within 28 days of COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: IS (OR 10.8 [95%CI 5.4 – 21.7]); CKD (OR 5.1 [95%CI 1.0 – 25.6]); DM (OR 4.2 [95%CI 1.7 – 10.6]); SCD (OR 3.4 [95%CI 1.1 – 10.6]). ND (OR 3.0 [95%CI 1.7 – 5.4]); and obesity (OR 2.0 [95%CI 1.1 – 3.9]). Notably, CHD, MTD, and PD were not independently associated with hospitalization. There was no effect modification of race/ethnicity on the association between obesity or DM and hospitalization.

Table 1: Characteristics of adolescents in our cohort

Figure 1. Association between comorbidities and hospitalization. Model 1: comorbidities only. Model 2: comorbidities, adjusted for race/ethnicity. Abbreviations: CKD – chronic kidney disease; SCD – sickle cell disease; ICS – inhaled corticosteroids.

Conclusion

IS, CKD, DM, SCD, ND, and obesity were associated with increased odds of hospitalization in adolescents presenting with mild to moderate COVID-19. Adolescents with these comorbidities should be prioritized for consideration of treatment with monoclonal antibodies.

Disclosures

Gabriella S. Lamb, MD, MPH, Nothing to disclose
583. SARS-CoV-2 Spike Protein S1/S2 Antibodies after Vaccination with Sinopharm in Peruvian Physicians
Authors: Lopera Maria , Vera Romina , Tapia Carlos , Cabrera Carlos , Gonzales-Zamora Jose , Alave jorge
Published: December 2021

Background

Peru started its national vaccination campaign in February 2021 using Sinopharm vaccine, targeting healthcare personnel on its initial phase. Although the immunogenicity of this vaccine was tested in clinical trials, there are no studies that evaluated the humoral response post vaccination in Peru.

Methods

We conducted a cross sectional study, which objective was to evaluate the humoral immunogenicity triggered by the Sinopharm vaccine in Peruvian physicians. We collected demographic and epidemiologic data via an electronic. The SARS-CoV-2 spike protein S1/S2 antibodies were measured by chemiluminescense (Liaison®). A positive test was defined as >15 U/ml, which has correlation of 95% with neutralizing antibodies measured by plaque reduction neutralizing test.

Results

92 participants were enrolled in the study. The epidemiologic characteristics are described in table 1. The mean level of antibodies measured at least 2 weeks from the second vaccine dose was 67.5 ± 70.5 U/ml. 85.7% of the study cohort had positive S1/S2 antibodies. In the univariate analysis, an imperfect negative correlation was found between the level of antibodies and participants’ age (r= -0.24; regression F test 5.25; p = 0.0242). A weak negative correlation was observed between the antibody titer and the time elapsed from the second vaccine dose and the day of antibody measurement (r= -0.17). A higher antibody level post vaccine was found in individuals who worked in COVID units (105.5 U / mL vs 58.2 U / mL; p = 0.0125), and in participants with history of COVID (216.5 U / mL vs 81.2 U / mL; p = < 0.0000). Hypertension was associated with lower antibody titers (36.9 U / mL vs. 74.6; p = 0.0464). In the multivariate analysis, working in COVID units, having previous COVID infection and shorter time from second vaccine dose and day of antibody measurement were associated with higher antibody levels post vaccine (table 2).

Conclusion

Our study showed that the time elapsed from the second vaccine dose and the day of antibody measurement, having previous COVID-19 infection and working in COVID -19 units may help to predict higher antibody titers post vaccine. Larger studies to evaluate the humoral response post Sinopharm vaccine and its clinical implications are still needed in Peru.

Disclosures

All Authors: No reported disclosures
584. Phase 1 Placebo-Controlled Trial of COVI-VAC™, an Intranasal, Live Attenuated COVID-19 Vaccine
Authors: Tasker Sybil , Bendel Daryl , Bevan Melissa , Mueller Steffen , Kushnir Anna , Londt Brandon , Robert Coleman J
Published: December 2021

Background

COVI-VACTM is an intra-nasal live-attenuated SARS-COV-2 synthetic viral vaccine being developed for the prevention of COVID-19. COVI-VAC is attenuated through deletion of the furin cleavage site and introduction of 283 silent deoptimizing mutations that maintain viral amino acid sequence but result in significant attenuation due to slow translation in the human host cell. Notably, COVI-VAC includes all viral antigens and is not limited to spike. COVI-VAC has demonstrated attenuation, immunogenicity and single dose protection in both Syrian golden hamster and non-human primate models.

Methods

48 healthy young adults were enrolled in an inpatient quarantine setting to one of 3 dose escalating cohorts and randomized to COVI-VAC or saline placebo given as nose drops, as a single 0.5mL dose or 2 doses 28 days apart. Endpoints included solicited and unsolicited adverse events, serum cytokines, viral shedding and sequence stability, mucosal and serum antibody responses and IFN ELISpot. Subjects will be followed for 1 year for late safety events and durability of immune response.

Results

Dosing is complete. There has been no trend in solicited reactogenicity events, and all unsolicited adverse events reported to date have been mild. There have been no SAEs or Grade 3 or 4 events. Vaccine virus from anonymized subjects was shed at levels lower than that likely to result in onward transmission, and the deoptimized sequence of the shed virus remained unchanged compared to the original vaccine sequence. Unblinded data including immunogenicity will be available prior to the IDWeek meeting.

Conclusion

COVI-VAC appears safe and well tolerated in healthy young adults. Vaccination resulted in minimal viral shedding without sequence instability. Safety and shedding data supports continued development in a wider Phase 2/3 population.

Disclosures

Sybil Tasker, MD, MPH, FIDSA, Codagenix Inc (Employee, Shareholder) Daryl Bendel, MD, Codagenix Inc (Scientific Research Study Investigator) Melissa Bevan, MD, Codagenix Inc (Scientific Research Study Investigator) Steffen Mueller, PhD, Codagenix Inc (Board Member, Employee, Shareholder) Anna Kushnir, PHD, Codagenix Inc (Employee) Brandon Londt, PhD, Codagenix Inc (Other Financial or Material Support, contracted lab services) J. Robert Coleman, PhD, Codagenix Inc. (Board Member, Employee, Shareholder)
585. Safety of Pfizer-BioNtech COVID-19 Vaccine in Healthcare Workers, Singapore
Authors: Kam Kai-Qian , Yung Chee Fu , Chong Chia Yin , Li Jia hui , Nadua Karen Donceras , Tan Natalie W , Thoon Koh Cheng
Published: December 2021

Background

On 14 December 2020, the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine was granted emergency use authorization in Singapore. Healthcare workers (HCW) were prioritized to receive the vaccine. We aim to investigate the side effects and risk factors for allergic reactions in our institution.

Methods

All HCW vaccinations were recorded in an electronic centralized database. All reactions occurring within a 30-minute observation period post vaccination were recorded. Staff were required to report any vaccine-related medical consult including hospitalization occurring within 14 days after vaccination. Moderate/severe reactions were assessed by a medical team and determined if the reactions were probable allergic reactions with consultation with an Allergist. We extracted data from 8 Jan 2021 to 30 April 2021.

Results

5030 and 159 HCW completed 2 doses and 1 dose of the vaccine respectively. There were 1056 HCWs (20.3%) with self-reported pre-existing allergy. There were 114 (1.1%) reactions occurring without the 30-minute observation period, and 64 (56.1%) were related to first dose of vaccine. The most common side effect experienced was aches or pain on any part of the body (n=46, 40.4%) followed by fatigue and/or giddiness (n=45, 39.5%), palpitations and/or shortness of breath (n=22, 19.3%), systemic rash and/or angioedema (n=12, 10.5%) and nausea and/or vomiting (n=12, 10.5%). A total of 23 HCWs complained of systemic rash and/or angioedema that occurred anytime post vaccination. Fifteen HCWs (0.29% of the cohort) were considered to have probable allergic reaction to the vaccine. None of the reactions were classified as anaphylaxis or severe reactions, but 4 HCWs required short hospitalization stay for observation. HCWs with pre-existing allergy had 2.6 times the risk of having probable vaccine-related allergic reaction than HCWs without pre-existing allergy (RR 2.6, 95% CI 0.9 to 7.3, p=0.068) but this was not statistically significant.

Conclusion

No anaphylaxis or severe reactions were observed in our institution. Acute side effects in our cohort were in line with published trial reports. We noted a raised relative risk of 2.6 of pre-existing allergy with probable vaccine-related allergic reaction but this was not statistically significant.

Disclosures

All Authors: No reported disclosures
587. An Intervention to Improve COVID-19 Vaccination Rates Among Inpatients at a Veterans Affairs Hospital
Authors: Fujita Ayako , Goolsby Tiffany , Powell Krista , Cartwright Emily J
Published: December 2021

Background

Hospitalizations are an opportunity to increase vaccine uptake and hospital-based strategies have been effective at increasing influenza and pneumococcal vaccination. Offering COVID-19 vaccination at discharge can reduce barriers to vaccination and target patients at high risk for severe illness and death. We evaluated a COVID-19 vaccine intervention implemented as part of routine discharge planning.

Methods

We trained healthcare personnel during April 2021 to review and document vaccine eligibility and interest for adult inpatients on medical, surgical, or psychiatric wards at the Atlanta VA Medical Center during discharge planning using a templated note in the electronic medical record (EMR). Outpatient vaccination center personnel were deployed to the participating wards daily (except Sundays) to facilitate vaccine administration at discharge. We measured the percentage of discharged patients with vaccine eligibility documented using the template and compared the number of patients vaccinated at discharge in the 4 weeks pre- and post-training. All Georgia adults became eligible for COVID-19 vaccines on March 25, 2021, prior to our intervention.

Results

Of the 769 patients discharged from one of the participating wards during the 4-week post-training, 474 (62%) had vaccine eligibility documented (Table 1). Of the 474 patients with documentation, 88 (19%) were eligible. Reasons for ineligibility included prior vaccination (n=266, 69%), patient refusal (n=103, 27%), and acute COVID infection (n=12, 3%). Of the 88 eligible patients, 61 (69%) received vaccination before discharge. In total, 16 of 793 inpatients in the pre-training period and 61 of 769 in the post-training period (2% vs 8%; p< 0.05) were vaccinated prior to discharge.

Table 1. COVID-19 vaccine eligibility and vaccination before discharge during the post-training period, reported by week

Conclusion

We found relatively high and sustained uptake of an intervention to screen hospitalized patients for COVID-19 vaccination eligibility. Creating a templated note in the EMR resulted in vaccination of nearly 70% of eligible patients prior to hospital discharge.

Disclosures

All Authors: No reported disclosures
588. Seroconversion Among Adults After Receiving At Least One Dose of a COVID-19 Vaccine: COVID-19 Community Research Partnership, Mid-Atlantic, Southeast and Southern United States, December 2020-May 2021
Authors: Friedman-Klabanoff DeAnna J , Tjaden Ashley , Santacatterina Michele , Munawar Iqra , Sanders John W , Herrington David M , Wierzba Thomas F , Berry Andrea
Published: December 2021

Background

Well-regulated clinical trials have shown authorized COVID-19 vaccines to be immunogenic and highly efficacious. Information about antibody responses after vaccination in real-world settings is needed.

Methods

We evaluated seroconversion rates in adults reporting ≥ 1 dose of an authorized COVID-19 vaccine in a U.S. multistate longitudinal cohort study, the COVID-19 Community Research Partnership. Participants were recruited through 12 participating healthcare systems and community outreach. Participants had periodic home-based serologic testing using either a SARS-CoV-2 nucleocapsid and spike IgM/IgG lateral flow assay (63% of participants) or a SARS-CoV-2 spike IgG enzyme-linked immunosorbent assay (37% of participants). The timing and number of tests before and after vaccination varied based on participant time in study. Participants were included if they were seronegative on the last test before and had >1 test result after vaccination (some had previously been seropositive, but seroreverted). A weighted Cox regression model with right censoring was used to obtain adjusted hazard ratios for sex, age, race/ethnicity, and prior seropositivity. Time-to-event (seroconversion) was defined as time to first positive test > 4 days after vaccination; participants were censored at the date of their last available test result.

Results

13,459 participants were included and 11,722 seroconverted (Table). Median time in study was 272 days (range 31–395). Median follow-up time from vaccine to last available test was 56 days (range 1–147). Participants had a median of 3 tests (range 1–12) before and 2 tests (range 1–8) after vaccination. Based on the Kaplan-Meier method, median time to seroconversion after first COVID-19 vaccination was 35 days (interquartile range: 25–45). Likelihood of seroconversion decreased with older age (Table). Female participants, non-Hispanic Black participants, and participants who were previously seropositive were more likely to seroconvert (Table).

Conclusion

All subgroups had high rates of seroconversion, with some small differences in likelihood of seroconversion between subgroups. These data demonstrate the excellent immunogenicity of COVID-19 vaccines in real-world settings in the US.

Disclosures

All Authors: No reported disclosures
590. Persisting COVID-19 vaccination hesitancy in the South Bronx
Authors: D' Aza Danelly Gomez , Shariff Masood A , Santibanez Israel Duran , Horowitz Raquel , Asad Hina , Mensah Dennis , Rabiee Lara , Pillai Anjana , Shah Vipul , Menon Vidya
Published: December 2021

Background

Minority groups have the lowest vaccination rates when compared to the overall population. We aim to study the attitudes and perceptions of COVID-19 vaccination, about six months after vaccine rollout in the South Bronx.

Methods

Cross-sectional anonymized online survey evaluating knowledge, attitude and perception about COVID-19 vaccination using SurveyMonkey™ was conducted in South Bronx community from April - June 2021.

Results

Of the 281 participants, 67% were Latinx and 16% were African American (AA); 69% (195) were fully vaccinated (FV) and 31% (86) with vaccine hesitancy (VH). The common reasons for hesitancy were “concerns about side effects” (38%), “vaccine is not safe” (27%) and “vaccine was approved too fast” (26%) (p< .001). VH were more likely to rely online/mobile apps (30%) and friends and family (23%) as compared to FV. VH were more likely to be AA, younger age (< 35 yrs), high school or lower education, single, unemployed, without comorbidities, not current on other eligible vaccines, and did not believe “vaccine is necessary to end the pandemic.” Majority of participants from both cohorts trusted their primary care providers. Mistrust with healthcare and pharmaceutical companies was higher in VH (p=0.009). Both groups preferred to continue wearing mask and practice social distancing despite vaccination status.

Table 1b: COVID-19 Vaccine Survey Summary

Table 1c: COVID-19 Vaccine Survey Participant Characteristics

Conclusion

Persisting vaccine hesitancy is concerning in minority communities. Identifying the target population and implementation of innovative methods to improve COVID-19 vaccination acceptance leveraging primary care providers would be a possible solution.

Disclosures

All Authors: No reported disclosures
591. Comparison of Fluconazole to Other Antifungal Agents in Allogeneic Hematopoietic Cell Transplant Recipients: A Meta-Analysis of Randomized Clinical Trials
Authors: Cheng Ce , Chineke Iloabueke , McBride Ali , Recio-Boiles Alejandro , Ainapurapu Lakshmi Saritha , Sun Chenyu , Vennelaganti Niharika
Published: December 2021

Background

Invasive fungal infections (IFI) are adverse complications of allogeneic and autologous hematopoietic stem cell transplantation (HSCT) with significant mortality and morbidity. Randomized Controlled Trials (RCT) have addressed the optimal anti-fungal prophylaxis regimen. However, the consensus for an anti-fungal prophylaxis regimen has remained elusive. Hence, we performed a meta-analysis of currently available RCTs comparing the efficacy of fluconazole vs. other antifungal agents including voriconazole, micafungin, and itraconazole in the endpoint of preventing IFI.

Methods

Randomized controlled trials were retrieved from PubMed, according to our inclusion criteria. The relative risk (RR), hazard risk (HR), and 95% confidence intervals (CI) were calculated. A random effect or fixed-effect model was used to calculate the pooled HR, based on heterogeneity. All statistical analyses were performed using RevMan software and R Core Team, and all p-values were two-tailed, and the significance level was 0.05.

Results

Ten RCTs were selected involving 2654 pts. Our results showed fluconazole is statistically inferior to other agents that include voriconazole, micafungin, and itraconazole with regards to the endpoint of a lower incidence of IFI (RR: 1.05; 95%CI: 1.02, 1.08; p=0.0002, I2=5%). However, subgroup analysis showed no statistical difference between fluconazole vs. other agents to prevent breakthrough proven IFI (HR: 0.76; 95%CI: 0.47, 1.23; p=0.27, I2=0%). Our subgroup analysis further showed that other agent’s group might have a superior role in preventing aspergillus compared with fluconazole (HR: 0.64; 95%CI: 0.44, 0.94; p=0.02, I2=0%), but no significant advantages over fluconazole for candidiasis (HR: 0.96; 95%CI: 0.45, 2.07; p=0.92, I2=0%).

Successful Rate Without Incidence of IFI

Figure 1. Successful Rate Without Incidence of IFI

Proven IFI vs. Suspected IFI

Figure 2. Proven IFI vs. Suspected IFI

Candidiasis vs. Aspergillus

Figure 3. Candidiasis vs. Aspergillus

Conclusion

This meta-analysis yield data that suggests fluconazole might be inferior to other agents in preventing IFI in all intent to treat patients undergoing HSCT. However, fluconazole is non-inferior in preventing proven IFI and candidiasis IFI based on our results. Thus, we continue to recommend fluconazole in selected patients who require anti-fungal prophylaxis. More RCTs are needed in the future to demonstrate the drug of choice for anti-fungal prophylaxis and address patient selection characteristics.

Disclosures

All Authors: No reported disclosures