bluuebunny/crossref_metadata_2025 huggingface dataset:
1055. Comparison of Scoring systems in Predicting Clinical Outcomes in Patients Hospitalized with COVID 19
Authors: Huang Anderson , Dieckhaus Kevin , Chirch Lisa M , Bath Roopjeet K , Abrantes-Figueiredo Jessica , Onwochei Jennifer , Holtzman Assaf , Tailor Neelam , Kuo Chia-Ling
Published: December 2022

Background

Previous scoring systems have been proposed to predict COVID19 outcomes, however none have been universally adopted. Two scoring systems of interest are Monoclonal Antibody Screening Score (MASS) and Oral Antiviral and Monoclonal Antibody Screening Score (OMASS). MASS prioritized patients for outpatient monoclonal antibody treatment based on risk of hospitalization, and OMASS was a modified version of MASS used to prioritize outpatient oral antivirals. We created a modified scoring system (UCH2021) incorporating vaccination status. These scores (table 1) have not been used to predict in-hospital clinical outcomes. We investigate these systems’ abilities to predict mortality and oxygen requirements in hospitalized COVID19 patients. They do not require blood tests and allow for more rapid triage. Table 1:MASS, OMASS, UCH2021 Scoring Criteria

Methods

A retrospective chart review was performed on 133 patients in two tertiary care centers between March and Sept. 2020 with RT-PCR confirmed SARS CoV2. Baseline risk factors were collected and MASS, OMASS, and UCH2021 were calculated. Primary outcomes included mortality, need for intubation, and need for supplemental oxygen >6L during hospitalization. Secondary analysis assessed if any individual risk factors were associated with those outcomes. These systems were evaluated via area under the curve calculations. Two groups based on an outcome were compared using two-sample t-tests for continuous variables and Fisher’s exact tests for categorical variables.

Results

All three systems demonstrated some discriminative power for mortality (table 2), but not for oxygen and intubation requirements. There was statistically significant difference in age between survivors and deceased (table 3), and BMI for oxygen requirements (table 4). Other risk factors were not predictive of mortality or oxygen requirement. Table 2:MASS, OMASS, UCH2021 Scores and Mortality in Hospitalized COVID19 PatientsTable 3:Age and Mortality in Hospitalized COVID19 PatientsTable 4:BMI and Oxygen Requirements in Hospitalized COVID19 Patients

Conclusion

The MASS, OMASS, and UCH2021 score all had predictive power in determining in-hospital mortality, with moderate accuracy, however none were predictive of oxygen requirements. Age and BMI were also good predictors of mortality and oxygen requirements respectively. This study was completed prior to vaccine distribution in the US. Further studies would be helpful to assess if UCH2021 score has greater discriminative power in samples with vaccinated patients.

Disclosures

All Authors: No reported disclosures.
1058. Development of a Steroid Stewardship Bundle to tackle the Glucocorticoid-Induced Hyperglycemia in COVID-19 patients: Results of SUPER Diabetes Study.
Authors: Issac Aleena , Kochuparambil Jose J
Published: December 2022

Background

Glucocorticoid therapy in COVID-19 patients poses a greater risk of hyperglycemia, leading to an unexpected detrimental effect on treatment outcomes. The Steroid Use in Patients Exhibiting Risk (SUPER) to Diabetes -SUPER Diabetes- study aimed to implement a steroid stewardship bundle to encounter the incidence of Glucocorticoid-Induced Hyperglycemia (GCIH) in COVID-19 patients and to evaluate the effectiveness of the Steroid Stewardship Program.

Methods

This interventional study included 600 COVID-19 confirmed patients admitted between April 2021and March 2022 in a secondary care hospital in India (stewardship cohort). A six-item Steroid Appropriate Index (SAI) assessed the need for steroid therapy using the parameters like the severity of disease, the onset of symptoms, weight of the patient, CT Thorax score, the preferred route of administration, and the comorbid disorders. This created a steroid stewardship bundle with the following parameters: (1) appropriate selection of the corticosteroid; (2) repeat blood sugar monitoring every 8 hours until discharge from hospital; (3) appropriate duration of therapy (4) proper de-escalation of dose/intravenous to oral switch. The patients were followed until discharge/death to track the incidence of hyperglycemia. The analysis of the effectiveness of SAI and the stewardship bundle was done by comparing this with the clinical outcomes among 300 COVID-19 confirmed patients admitted before implementing the scale (retrospective cohort).

Results

The majority of the patients included in the stewardship cohort were males (367; 61.1%), and the mean age was 47.3± 17.1 years. The incidence of new-onset of hyperglycemia or a worsened glycemic profile, i.e., Glucocorticoid-Induced Hyperglycemia (GCIH), was more among the retrospective cohort when compared with the stewardship cohort (32.1% vs 6.3%), p< 0.001). The study also revealed that history of diabetes (p< 0.001), age (p=0.002), number of medicines used for treatment (p< 0.001), and the frequency of monitoring of diabetes (p< 0.001) are significantly associated with GCIH.

Conclusion

Implementing the steroid stewardship bundle significantly improved the appropriate selection and use of corticosteroids, decreasing the incidence of associated adverse events.

Disclosures

All Authors: No reported disclosures.
1073. SARS-CoV-2 Vaccine-Induced Immunogenicity among Hematopoietic Stem Cell Transplant Recipients (HSCT)
Authors: Kokogho Afoke , Aleissa Muneerah M , Chang Jun Bai Park , Walsh Stephen R , Crowell Trevor A , Baden Lindsey R , Sherman Amy C
Published: December 2022

Background

SARS-CoV-2 vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), but immunogenicity may be reduced in patients undergoing hematopoietic stem cell transplantation (HSCT). The variables that impact the humoral response, such as age, gender, disease and transplant type, prior treatments, and vaccine type, have not been comprehensively described.

Methods

A retrospective review was conducted at a single-centre of HSCT recipients who received COVID-19 vaccinations between 2020 and 2021. Participants were included if >18 years and had received at least a single dose of Pfizer, Moderna or Johnson & Johnson (J&J) vaccine. Anti-Spike (S) IgG titers were quantitatively measured at provider discretion during routine care using the Roche Elecsys Anti-SARS-CoV-2 spike immunoassay and categorized as Responders (< 0.8U/mL) and Non-responder (>0.8). Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for Responders vs Non-responders. Controlled risk factors included; Age, disease, treatments, and history of graft-versus-host disease (GVHD).

Results

Of 117 HSCT patients assessed, 59 (50.4%) were female, 106 (90.6%) were white, and the median age was 62.5 years (interquartile range [IQR, 49.9-67.8). Vaccinations were administered at a median of 179 days post-transplant (IQR 319 - 105) and antibody responses were measured at a median of 135.5 days post-vaccination (IQR 190-50). 106(90.6%) were responders with a mean titre of 1141.5U/mL (SD=1095.3). 35% had Low (< 100U/mL) titres. Being Female (OR 0.02, 95%CI 0.003 - 0.6) was associated with a slightly higher odds of being a responder.

Conclusion

Hematopoietic stem cell transplant recipients demonstrated a high prevalence of anti-S IgG antibody positivity following COVID vaccination. However, neither patient characteristics nor treatment regimens were seen to be strongly associated with anti-S protein positivity among HSCT recipients. More studies are needed to further characterize patient and treatment characteristics that correlate with seroprotection among these patients.

Disclosures

Stephen R. Walsh, MD, Janssen Vaccines: Grant/Research Support|ModernaTX: Grant/Research Support|Sanofi Pasteur: Grant/Research Support.
1088. Evaluating the Effect of Donepezil on Mortality Among Alzheimer’s Disease Patients With and Without COVID-19 Infection
Authors: Bej Taissa A , Edmiston Elizabeth , Wilson Brigid , Phillips Joy , Jump Robin L
Published: December 2022

Background

Dementia has been identified as an independent risk factor for increased severity of COVID-19 infection. Donepezil, a cholinesterase inhibitor approved for Alzheimer’s disease (AD), has anti-inflammatory properties. Previous studies have found that donepezil reduced all-cause mortality for people living with AD. The anti-inflammatory effects of donepezil have not been studied in patients with COVID-19 and AD. Here, we compare mortality rates of patients with AD to assess the impact of donepezil on the severity of COVID-19 infections.

Survival following SARS-CoV2-2 test, stratified by result and Donepezil

Kaplan-Meier curves of all-cause mortality for Veterans with Alzheimer’s Disease taking donepezil (black) compared to those who were not taking donepezil (grey), further stratified by those with a positive SARS-CoV-2 PCR test (solid lines) or no evidence of a COVID-19 infection during the study period (dashed lines). While donepezil has a positive effect on survival, the adjusted survival odds ratio is not greater among those with vs. without a COVID-19 infection.

Methods

Using administrative data from the Veterans Healthcare Administration (VHA), we conducted a national retrospective cohort study of Veterans with AD who were tested for SARS-CoV-2 between March 1, 2020 and December 31, 2021 in the VHA. Among these patients, we assessed all-cause 30-day mortality stratified by COVID-19 infection and donepezil use and considered the interaction of these two factors. For Veterans with a positive test, the date of first positive test was used to assess mortality; for Veterans without a COVID-19 diagnosis or positive test, date of first negative test was used.

Results

During the study period, 582 Veterans with Alzheimer’s disease were positive for COVID-19 and 14430 had no test or diagnosis indicating COVID-19 infection. Among people with AD and COVID-19, all-cause 30-day mortality was 29% (47/163) for people taking donepezil compared to 38% (159/419) for those who were not. Among people with AD without COVID-19, all-cause 30-day mortality was 5% (189/4189) for people taking donepezil compared to 7% (712/10241) for those who were not. In a multivariable logistic regression, the decrease in mortality associated with donepezil did not differ between people with and without COVID-19 (OR (95% CI) = 0.71 (0.47, 1.07) vs. OR (95% CI) = 0.68 (0.57, 0.80), interaction P = 0.818).

Conclusion

While all-cause mortality was lower for patients taking donepezil compared to those not taking donepezil, the protective effect of donepezil was not increased in AD patients with COVID-19 over those without COVID-19. The population differences and inflammatory biomarkers of AD patients treated with and without donepezil merit further study.

Disclosures

Robin L. Jump, MD, PhD, Merck: Grant/Research Support|Pfizer: Advisor/Consultant.
1090. Factors effecting mortality among Covid-19 patients in Renal Transplant Recipients from a single center in Pakistan
Authors: Nasim Asma , Kumar Sunil
Published: December 2022

Background

Corona virus disease-19 (Covid-19) has significantly affected organ transplantation with concerns regarding severe infection and mortality. Data on Covid-19 in renal transplant recipients (RTRs) is scarce from Pakistan. The aim of this study is find out the factors effecting mortality among Covid-19 patients in renal transplant recipients from the largest transplant center of Pakistan.

Methods

All RTRs >18 years, with positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) and diagnosed as severe disease, between April to December 2020 were retrospectively reviewed. The severe disease was defined as O2 saturation < 94% at room air on admission. Survivors and non- survivors were compared. Demographics, immunosuppression, comorbid conditions, clinical features, laboratory investigations and graft function were noted.

Results

A total of 95 RTRs had severe disease. There was no difference in mortality between age, gender and co-morbid conditions among survivors and non-survivors. Both groups received similar immunosuppressive regimen. Intensive care unit (ICU) admission [16.5% vs 68.8% p< 0.001 OR 11.17 95% CI (3.3-37.6)] and high D-dimers >1.5µg/ml (p=0.052) at the time of admission were significantly associated with mortality. There was no association of graft function with mortality. Treatment with methyl-prednisolone was found to be significantly associated with survival [83% vs 43% P=0.02 OR 0.15 95% CI (0.05-0.49)]. (Table 1) WHO grading of the disease is shown in figure 1, there was a 100% mortality among patients on mechanical ventilator. Figure 1:WHO clinical grading of severe diseaseTable 2:Comparison between survivors and non-survivors among patients with severe disease

Conclusion

ICU admission and high D-dimers at the time of admission are the significant risk factors for mortality in patients with Covid-19 infection. There was no association of graft dysfunction with mortality. Steroids use has significantly improved survival in renal transplant recipients with severe Covid-19 infection.

Disclosures

All Authors: No reported disclosures.
1096. Riding the Waves: Infection by SARS-CoV-2 Variants in Solid Organ Transplant Recipients at Texas Children’s Hospital
Authors: Buffaloe Leanne , Bocchini Claire , Moulton Elizabeth A , Ruderfer Daniel , Deray Kristen Valencia , Munoz Flor M
Published: December 2022

Background

Texas Children’s Hospital is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exist about SARS-CoV-2 infection (COVID-19) in the pediatric SOT population. We evaluated the impact of different SARS-CoV-2 variants in a cohort of PCR positive SOT recipients.

Methods

SOT recipients with a positive SARS-CoV-2 PCR test from 3/1/2020 to 2/28/2022 were included in the cohort. The study period was divided into 3 eras based on the predominant circulating variant of SARS-CoV-2: 3/20-6/21 original strain/Alpha, 7/21-11/21 Delta, and 12/21-2/22 Omicron variants. Retrospective medical record review was performed; Chi-squared and Fischer exact test were used to compare groups.

Results

A total of 269 of 1031 (26%) SOT recipients tested positive for SARS-CoV-2 during the study period. By organ, 87/335 (26%) heart, 57/224 (25%) kidney, 92/405 (23%) liver, and 25/67 (37%) lung recipients had COVID-19 infection. By era, there were 99 (37%) original strain/ Alpha, 65 (24%) Delta, and 105 (39%) Omicron. The patients’ median age was 12.72 years (IQR 6.6, 15.1) with a minority of recipients being female (42%). Common comorbidities included hypertension (50%), obesity (13%), diabetes (10%), and chronic kidney disease (10%); 34% had no comorbidities aside from chronic immunosuppression post-transplant. Overall, 80% of recipients were symptomatic (Figure 1), and 50 (19%) required hospitalization. Hospitalization rates were highest (29%) during Delta, compared with 18% for original/Alpha and 13% for Omicron (p=0.02) eras. Need for respiratory support, ICU admission, and all-cause mortality did not vary by era (Table 1). Three SOT recipients (2 original/Alpha and 1 Delta) were diagnosed with multi-inflammatory syndrome in children (MIS-C).

Conclusion

Our study suggests that pediatric SOT recipients have a high risk for hospitalization and short-term complications with COVID-19; Omicron appears to cause less severe disease, including MIS-C. Additional studies are needed to understand long-term complications of COVID-19 in SOT recipients.

Disclosures

Elizabeth A. Moulton, MD, PhD, Pfizer: Grant/Research Support Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB.
1099. SARS-CoV-2 Positive Pregnant Women Delivering in a Hospital From March 2020 – February 2021 in Three California Counties
Authors: Hall Brenna , Lee Jane E , Kirley Pam Daily , Roland Jeremy L , Hundal Kareena
Published: December 2022

Background

Comparing outcomes of both symptomatic and asymptomatic hospitalized pregnant women with COVID-19 can inform both the prognosis during hospitalization for pregnant women with COVID-19 and the relationship of COVID-19 to pregnancy outcomes.

Methods

Using population-based surveillance data from COVID-19 Associated Hospitalization Surveillance Network (COVID-NET), chart reviews were conducted for SARS-CoV-2 positive pregnant patients, age 15 to 49 years, residing in Alameda, Contra Costa, and San Francisco Counties in California who delivered in a hospital between March 1st 2020 and February 28th 2021. Cases were defined as SARS-CoV-2 positive if they had a positive test during hospitalization or within 14 days prior to admission. Multivariate analysis was used to describe demographic characteristics, underlying medical conditions, vaccination status, and pregnancy outcomes by presence or absence of symptoms upon hospitalization. Chi-square tests assessed significance with p-values < 0.05 considered statistically significant.

Results

Among the 330 SARS-CoV-2 positive women that delivered in a hospital, 60.3% were Hispanic or Latino, 4.9% were White (Non-Hispanic), 6.4% were Black (Non-Hispanic), 6.7% were Asian or Pacific Islander, 0.9% were multiracial, and 20.9% were unknown race or ethnicity. Symptomatic cases spent a median of 3 days in the hospital while asymptomatic cases spent a median of 2 days in the hospital. Symptomatic women were more likely to have a Caesarian-section (OR 2.49, 95% CI: 1.45, 4.28), have preeclampsia (OR 2.19, 95% CI: 1.17, 4.10), and be admitted to the ICU (OR 3.78, 95% CI: 1.08, 13.29) than asymptomatic women. Invasive mechanical ventilation was required for 3 of the 109 symptomatic women and none of the 221 asymptomatic women (P=0.03).

Conclusion

Among hospitalized SARS-CoV-2 positive patients in three California countries from March 1st 2020 to February 28th 2021, symptomatic pregnant women were more likely to have a Caesarian-section, have preeclampsia, and be admitted to the ICU compared to asymptomatic pregnant women. As COVID-19 continues to be prevalent, future studies should examine the associations and potential confounders between COVID-19 symptoms and pregnancy outcomes.

Disclosures

All Authors: No reported disclosures.
1104. A comparison of remdesivir versus remdesivir plus tocilizumab for patients with severe COVID-19 in the Dominican Republic
Authors: Roque Yori A , Luna David De , Mena Lora Alfredo J , De la Nuez Liz , Hernando Ana , Jimenez Cesar , Morel Rommel , Pichardo Maily
Published: December 2022

Background

The COVID-19 pandemic has strained healthcare systems worldwide and is now a leading cause of death. Remdesivir is the first antiviral shown to decrease time to recovery in a randomized placebo-controlled trial. Other studies have conflicting results and the World Helath Organization does not recommend the routine use of Remdesivir in hospitalized patients. The herogeneity of these studies and their populations makes interpretation of the available data difficult, with standard of care in different countries as the main confounding factor. Thus, it is imperative for low and middle income countries to study the role of remdesivir within their healthcare systems. We seek to further understand the impact of COVID-19 in a cohort in the Dominican Republic.

Methods

This is a retrospective review of patients admitted for COVID-19 to a tertiary center in the DR between August 2020 to March. 2021. Patients with clinical findings consistent with COVID-19 pneumonia and a positive molecular test for SARS-CoV-2 were included in the study.

Results

A total of 59 cases were reviewed, of which 40 were treated with remdesivir and 19 with remdesivir plus tocilizumab. Patients were more commonly male (69.5%) and ages ranged from 71-80 years (34.5%), 61-70 (20.7%), 51-60 (20.7%), 41-50 (10%), >81 (8.6%) and 18-30 (1.7%). Hypertension was the most common comorbidity (Figure 1). The average length of stay was 16.5 days, and 2.1 days. Mechanical ventilation was needed in 33.9%. Tocilizumab was administered in 32%. Mortality for the cohort was 29% (Figure 2). Mortality in patients treated with remdesivir alone was 22%, compared to 6.8% in those receiving tocilizumab and remdesivir.

Comorbidities

Mortality by length of stay

Conclusion

In our cohort, the use of remdesivir was associated with higher mortality than remdesivir in combination with tocilizumab. The mortality in our cohort was high (29%) compared to the 11.9% reported in in the placebo group of the ACTT-1 study. Furthermore, studies have consistently shown benefit earlier in the disease course and with lower oxygen needs. Our cohort had high rates of mechanical ventilation. Thus, the modest benefit seen in developed countries may be harder to show in resource limited settings and the number needed to treat is likely much higher. Remdesivir did not appear to have an impact in our cohort.

Disclosures

All Authors: No reported disclosures.
1107. A Survey on Remdesivir Use and Antimicrobial Stewardship Restrictions Throughout the COVID-19 Pandemic
Authors: Mena Lora Alfredo J , Herald Fischer , Burgos Rodrigo M , Borgetti Scott , Lindsey Brenna , Chaisson Lelia H , Bleasdale Susan C
Published: December 2022

Background

Remdesivir (RDV) was the first agent with proven clinical benefit against COVID-19, shortening the time to recovery in a randomized placebo-controlled trial (RCT). Based on this trial, the Food and Drug Administration approved RDV via emergency use authorization. Despite its wide use, RDV remains controversial. Early use of RDV in patients requiring low flow nasal canula has robust evidence. However, benefit in mechanical ventilation (MV), high-flow nasal canula (HFNC) and non-invasive positive pressure ventilation (NIPPV) is conflicting. Multiple studies, most notably the SOLIDARITY and DisCoVeRy trial, have conflicting results on who benefits from RDV. Deploying novel therapeutics in this changing landscape is challenging. We seek to understand RDV practices and the role of antimicrobial stewardship (ASP) in hospitals across the US.

Methods

A survey was developed and disseminated through Infectious Diseases Society of America (IDSA) IDea network, IDSA Antimicrobial Stewardship Centers for Excellence and the Society for Healthcare Epidemiology messaging boards. Data collected included city, presence of RDV therapeutic restrictions, and RDV use by degree of oxygen needs for each COVID-19 wave.

Results

A total of 78 responses were collected, representing wide geographic reach in the US (Figure 1). RDV was restricted in 53% of facilities. Hospitals without restrictions commonly used RDV for patients on MV, NIPPV and HFNC, with more use on HFNC than on NC during the first winter, Delta and Omicron waves (Figure 2). Use on MV declined with each surge. Hospitals with RDV restrictions had more use of RDV on NC than all other ordinal scales (Figure 3). Use in MV, NIPPV and HFNC compared to NC declined in the restricted group with each COVID-19 surge. Figure 1.Geographic distribution of hospitals represented in the survey

Figure 2. Remdesivir use by oxygen requirements in hospitals without remdesivir therapeutic restrictions.

Figure 3 Remdesivir use by oxygen requirements in hospitals without remdesivir therapeutic restrictions.

Conclusion

A wide gap between evidence-based guidelines and actual practice exists. This gap was wider in hospitals without COVID-19 therapeutic restrictions in place for RDV. In the unrestricted group, RDV was commonly used for MV, HFNC and NIPPV, where robust RCT evidence of benefit is lacking. Though this practice occurred in both groups, the restricted RDV group prioritized RDV use in NC and did so at higher percentages each subsequent COVID-19 surge. ASP restrictions can have an important role in guiding COVID-19 therapy.

Disclosures

All Authors: No reported disclosures.
1120. Descriptive Analysis of Monoclonal Antibody Administration for Pregnant Patients with SARS-CoV-2 Infection
Authors: Vikraman Praveen Kumar , Chang Kai Ming , Doan Thien-Ly , Donaghy Henry
Published: December 2022

Background

We studied the safety and efficacy of the use of monoclonal antibodies (MAB) against SARS-CoV-2 in pregnant women who developed COVID-19 infection.

Methods

We conducted a cross-sectional descriptive multi-center study of pregnant patients who developed SARS-CoV-2 infection from January 2021 to January 2022 and received MAB therapy. Primary outcomes assessed were infusion-related adverse events and pregnancy outcomes within one month of MAB infusion. The secondary outcomes assessed were hospitalization and ICU admission for COVID19 infection and thirty-day all-cause mortality.

Results

141 patients were included in the study (median age 33 +/- 5.3 SD, median BMI 28.9 +/- 8.42 SD). In terms of COVID vaccination status, 49.6% received one dose, 36.1% were fully vaccinated, and 7% received the booster dose. Most patients received casirivimab/imdevimab (105, 74.5%) followed by sotrovimab (33, 23.4%). Four patients developed adverse reactions to MAB infusion (two grade-2 reactions and two grade-1 reactions as per the National cancer institute infusion reaction grading criteria). Only one patient (0.7%) was hospitalized for COVID-19 infection, however, she was not hypoxic nor required ICU admission. Five patients delivered within four weeks of MAB administration, however, four of those patients were of gestational age > 37 weeks. Data for 30-day all-cause mortality was available on 88.7% (125) of the patients and data for 30-day pregnancy adverse outcomes was available on 86.5% (122) of the patients due to lack of follow-up within the Health System. There was no reported 30-Day all-cause mortality within the cohort. Two patients (1.4%) had premature rupture of the membrane and one patient (0.7%) had premature delivery within 30 days of receiving MAB. Two patients had preeclampsia (1.4%) and one patient (0.7%) was admitted for evaluations of decreased fetal movements.

Conclusion

Administration of monoclonal antibodies against SARS-CoV-2 was well tolerated during pregnancy. Only 4 out of 141 (2.8%) had mild to moderate infusion-related reactions. The 30-day pregnancy adverse outcomes observed were well below the mean background rate. There was no reported mortality among MAB recipients and only one patient was hospitalized for mild COVID19 infection.

Disclosures

All Authors: No reported disclosures.
1125. Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalized adults with severe COVID-19 pneumonia: an open-label randomized trial.
Authors: Gutierrez Carlos Dueñas , Abadia-Otero Jesica , Cusacovich Ivan , Martín-González Jose Ignacio , Muela-Molinero Alberto , Corral-Gudino Luis , González-Fuentes Roberto , de Temiño Ängela Ruíz , Moral Elena Tapia , Cuadrado-Medina Francisca , Martín-Asenjo Miguel , Gonzalez Pablo Miramontes , Delgado Morales Jose Luis , Ines Sandra , Abad-Manteca Laura , Usategui-Martín Iciar , Ruíz-Albí Tomás , Miranda-Riaño Sara , Rodríguez-Fortúnez Patricia , Rodríguez-Jiménez Consuelo , López-Franco Esperanza , Marcos Miguel
Published: December 2022

Background

Pulse glucocorticoid therapy is used in COVID-19 infection. We evaluated the

effectiveness of methylprednisolone 250 mg/d for 3 days vs. dexamethasone 6 mg/d for 10 days in patients with severe but not critical COVID-19 pneumonia.

Methods

A multicentre, randomized, open-label, controlled trial was conducted between February 2021 and August 2021 at 4 hospitals in Spain and included 128 hospitalized adults with confirmed COVID-19 pneumonia needing oxygen therapy but not critically ill. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 once daily for 10 days or methylprednisolone 250 mg once daily for 3 days. The primary outcome was 28-day mortality.

Results

Of the 128 randomized patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group vs. 4.8 % in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, -8.8 to 9.1%]; P=0.98). The post-hoc added composite outcome of mortality at 90 days or intubation was 15.9% in the 250 mg methylprednisolone group vs. 15% in the 6 mg dexamethasone group (absolute risk difference, -0.9% [95% CI, -13.8 to 12.3%];P=0.83). Hyperglycaemia was more frequent in the methylprednisolone group, at 27.0 vs. 8.1 % (absolute risk difference, -18.9% [95% CI, -31.8 to - 5.6%]; P=0.007).

Conclusion

Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.

Disclosures

Carlos Dueñas Gutierrez, MD, ViIV, GILEAD, Jannsen, MSD: Lecture fees.
1129. Efficacy of a Polyclonal Ovine Fab (PR020) Against SARS-CoV-2 Infection
Authors: Bascal Zainab , Griffiths Aled , Dentten Ellen , Hill Christon , Ward Suzanne
Published: December 2022

Background

Passive immune therapies may be useful in mitigating severe COVID-19. The hamster model has been successfully used to study efficacy of COVID-19 treatments. Our objective with this research is to demonstrate initial efficacy of a new polyclonal ovine Fab raised against the SARS-CoV-2 spike protein (PR020) as a treatment for COVID-19.

Methods

Hamsters were treated with PR020 via intraperitoneal route at a dose of 120 mg/kg or a vehicle control once every 24 hours for 8 days, starting 1 day prior to viral challenge with Victoria/1/2020 SARS-CoV-2. Sampling to detect viral RNA and clinical observations were taken throughout the challenge phase. Necropsy occurred 1 day following the last dose of PR020, and tissues were assessed for histopathology and viral RNA.

Results

Hamsters receiving vehicle alone lost weight more rapidly than the PR020 group (Figure 1, p< 0.05 day 4 onward). Clinical illness scores for the PR020 group were lower compared to control animals (Figure 2, p< 0.05 day 3 onward). While viral shedding assessed by throat swab did not differ between groups, viral RNA levels in lung tissue was significantly lower in PR020-treated animals (Figure 3, p< 0.05). PR020-treated animals also showed significantly less pathological changes in the lung compared to controls (Figure 4, p=0.0022). FIGURE 1.Weight of Hamsters Receiving PR020 Compared to Controls.FIGURE 2.Clinical Scores of Hamsters Receiving PR020 Compared to Controls.FIGURE 3.Viral RNA Levels in Lungs of Hamsters Receiving PR020 Compared to Control.

Conclusion

Treatment with PR020 resulted in a positive clinical outcome (e.g. less weight loss and lower clinical signs). While treatment appeared to have little effect in the nasopharynx, there was a positive effect in the lower respiratory tract, with substantially less viral RNA in the lungs of the group given PR020 and a decrease in the lung histopathology, including consolidation. FIGURE 4.Histopathology Results: Lung Consolidation Scores and Total Histopathology Scores for Lung and Nasal Cavity.

Disclosures

Zainab Bascal, PhD, BTG International Inc: Employee Aled Griffiths, BSc, BTG International Inc: Employee of BTG Ellen Dentten, PhD, BTG International Inc: Employee of BTG Christon Hill, BSc, MBA, BTG International Inc: Employee of BTG Suzanne Ward, PharmD, BTG International Inc: Employee of BTG.
1146. Real-World Experience Highlighting Tocilizumab Use in the Treatment of COVID-19
Authors: Maguire Christina , Terico Adrienne , Patel Hinal , Anesi George L , Degnan Kathleen , Dutcher Lauren , Hamilton Keith W , Meyer Nuala J , Talati Naasha J , Saw Steve
Published: December 2022

Background

Tocilizumab (TCZ) was approved by the Food and Drug Administration under emergency use authorization for treatment of COVID-19 in patients requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Despite multiple clinical trials, there remain unanswered questions surrounding TCZ use.

Methods

This multi-hospital retrospective cohort study included patients who received TCZ for COVID-19 between January 29th, 2021 and June 30th, 2021 at five University of Pennsylvania Health System (UPHS) hospitals. Patients were eligible for TCZ per UPHS criteria if they scored ≥ 5 on the World Health Organization (WHO) ordinal scale for ≤ 24 hours and experienced < 14 days of acute COVID-19 symptoms. Descriptive statistics were performed to characterize usage within the health system.

Results

This study evaluated 134 patients who received TCZ for the treatment of COVID-19. TCZ was ordered a median of 22 hours (interquartile range [IQR], 13.2 – 41.5) after hospital admission. A majority of patients (76.1%) were admitted to the intensive care unit and a small portion (12.7%) had a WHO ordinal scale that was >5 at time of TCZ order entry. All patients received concomitant dexamethasone therapy at a total prednisone equivalent of 400 mg (IQR, 335.6 – 480). Overall 33.6% of patients experienced an adverse event (ADE) within 30 days of TCZ administration (Table 1). Most common ADEs included bacterial infection (29.9%), hepatitis (6.7%), and fungal infection (3%); other etiologies of ADEs were not accounted for. All-cause mortality (Table 2) at day 30 occurred in 20.9% of patients and median time from TCZ administration to mortality was 12.5 days (IQR 5 – 18.3). Ninety-six patients in the cohort (71.6%) were discharged by day 30. Of the subgroup discharged by day 30, the majority (70.8%) were discharged to home.

Conclusion

Patients who received TCZ for severe COVID-19 experienced 20.9% mortality; mortality was higher among those with higher ordinal scale at the time of TCZ dosing. A large portion of patients (70.8%) were discharged to home within 30 days. One third of patients experienced an adverse event, primarily bacterial or fungal infection. Our experience may be useful in counseling patients about anticipated effects of TCZ.

Disclosures

George L Anesi, MD, MSCE, AHRQ, NHLBI, UpToDate: Advisor/Consultant|AHRQ, NHLBI, UpToDate: Grant/Research Support Kathleen Degnan, MD, Gilead: Grant/Research Support.
1157. The Clinical Impact of Casirivimab–Imdevimab Monoclonal Antibody Therapy (CIMAT) in COVID-19 patients: A real-world insight from India.
Authors: Kochuparambil Jose J , Issac Aleena
Published: December 2022

Background

Various clinical studies from developed countries support the use of Casirivimab–Imdevimab Monoclonal Antibody Therapy (CIMAT) to treat outpatients with mild to moderate coronavirus disease-19 (COVID-19). However, the real-world clinical data from India, owing to the portrayed benefits, are limited. Moreover, the choice of CIMAT depends upon the willingness of the patient or his bystanders for this therapy. The study aimed to assess the impact of Casirivimab–Imdevimab Monoclonal Antibody Therapy (CIMAT) for mild to moderate COVID-19 in India.

Methods

A single-center, retrospective comparative study was conducted to evaluate the impact of the CIMAT in symptomatic adult COVID-19 patients admitted to a secondary care hospital in South India, categorized as mild or moderate, and who are at high risk for progression to severe COVID-19. The data for the study were retrieved from the Electronic Health Records (EHR) of the hospital from April 2021 to March 2022, a period of 12 months. The primary outcome of the study was the length of hospitalization, and the secondary outcomes were mechanical ventilation post-infusion, readmissions after discharge, and mortality rate. Outcomes in the CIMAT cohort were compared to those of a control group of patients admitted with a diagnosis of SARS-CoV-2 during the same period who were qualified for CIMAT but were unwilling to administer it.

Results

This study included 474 patients, 48 in the CIMAT cohort and 426 in the control group. In the CIMAT cohort, the median age was 65 years (IQR: 50–73); 56.2% were ≥65 years old; 54.3% were males. Patients on CIMAT compared to the control group had a lower length of hospitalization(median: 4 [IQR 1–8]), lesser requisite for mechanical ventilation (4.3% vs 20.8%, p < 0.001) and less frequent readmissions within 10 days post-discharge (6.5% vs 9.3%, p < 0.001). Mortality was more among the control group, i.e., 22 (5.1%), and only one patient in the CIMAT cohort died during hospitalization (p = 0.23). The majority of the patients in the CIMAT cohort (41[89.1%]) were symptom-free within seven days of antibody cocktail administration.

Conclusion

Patients treated with CIMAT for COVID-19 were more clinically benefitted than those treated without the antibody cocktail.

Disclosures

All Authors: No reported disclosures.
Spatial Dimensions of Structural Change
Authors: Dore Poornima , Narayanan K.
Published: December 2022

This Chapter provides the conceptual and analytical framework for the book by outlining the spatial dimensions of structural change and drawing from various theoretical paradigms. These are closely linked with the phenomenon of specialization and division of labour along with empirical studies which help trace the pattern of agglomeration and regional development. Sectoral diversification is found to be a significant factor in the Indian experience and various studies point towards the need for greater empirical evidence on agglomeration in the context of developing countries.
Trends and Patterns of Regional Economic Development
Authors: Dore Poornima , Narayanan K.
Published: December 2022

This chapter attempts to describe and characterise the broad trends and patterns of regional development in India along with preparing a typology of clusters of all regions. Moving from the pan-India story to state level analysis, it maps out the trends in geographic distribution of economic structure and activities at a regional level.
The Man behind the Curtain
Authors: Bunch Ryan
Published: December 2022

The life and times of L. Frank Baum are the context for the theatrical humbug and American performances of the novel The Wonderful Wizard of Oz (1900) and the musical extravaganza The Wizard of Oz (1903). Baum’s book has fairy tale qualities and American traits that accommodate its adaptation as a musical. The extravaganza stages carnivalesque performances of American identity using the musical theater conventions of the turn of the twentieth century. These performances reflect attitudes about race, gender, and the performance of self in the theatrical cultures of the immigrant “melting pot” and family entertainment in the Progressive Era. The humbug of fairy tales and theater in these literary and theatrical texts establish the theatrical orientation of Oz and its American utopianism continued in subsequent musicals based on The Wizard of Oz.
Introduction
Authors: Quin Jack
Published: December 2022

The introduction begins by offering a brief vignette about the centrality of sculpture to Yeats’s writing and thinking by recounting the unveiling of Henry Moore’s Standing Figure: Knife Edge sculpture in the Yeats memorial garden, St. Stephen’s Green, Dublin in 1967. The second section provides an outline of the monograph chapters; the third and final section surveys the relevant criticism and recent reassessments of Yeats’s ekphrastic poetry and inter-art collaborations in order to show the importance of a holistic re-evaluation of Yeats’s work. The introduction argues that the conflation of art forms in literary criticism under the aegis of “visual culture” or “the visual arts” risks marginalizing the art of sculpture. While documenting how poetic form draws analogies to sculptural form in a selection of poems, Yeats’s understanding of sculptural practice and his sustained conversations, at times collaborations, with particular sculptors, attest to a more complicated and less metaphorical use of the art of sculpture in his writings.
Senator Yeats and the Free State Coinage
Authors: Quin Jack
Published: December 2022

The third chapter begins by examining Senator Yeats’s role in designing the new Free State coinage from 1926 to 1928, as chairman of the committee charged with soliciting artists and recommending designs. Despite the wealth of evidence demonstrating Yeats’s interest in coins and medals, his appreciation of coins as an art form and his role in designing the coinage have not received sustained critical attention. This chapter considers coins as low-relief sculpture, connected to his deep interest in sculpture and European sculptors such as Carl Milles and Ivan Meštrović. The chapter isolates the singular contributions but also the frustrations that Yeats faced in his role as committee chairman, with reference to government documents, Yeats Library materials, and recent research into the political context of redesigning the coinage. In so doing, the chapter situates Yeats’s various poetic engagements with coins from “Brown Penny” (1910) to “Parnell’s Funeral” (1935) within a complex negotiation of the coin as a visual arts medium of portraiture in ekphrastic episodes, as a durable talisman that records and transmits ancient myths, or as a structural metaphor for the poem itself. The final section of the chapter evaluates Yeats’s writings and speeches on monuments during his Senate tenure within the wider context of debates over controversial statues to British statesmen and monarchs in a newly independent Ireland.
Pound, Vorticism, and the Sculpture of Brancusi
Authors: Quin Jack
Published: December 2022

This chapter explores modernist approaches to poetry and sculpture by documenting Yeats’s engagement in a substantial body of art writing centered on the Romanian sculptor Constantin Brancusi. Ezra Pound is identified as a totemic figure in a prevailing schema of modernist sculptural poetics that has adopted or appropriated the work of Jacob Epstein, Henri Gaudier-Brzeska, and Constantin Brancusi. Yeats’s own fragmentary but astute engagements with these same figures and sculptures provides an alternative but no less modernist idea of sculptural aesthetics. Pound’s and Gaudier-Brzeska’s contributions to Blast, The Dial, The Little Review, and other little magazines receive close attention in the opening section. Subsequent sections examine Yeats’s “Lapis Lazuli,” the discussion of Brancusi in each version of A Vision (1925; 1937), and in a neglected verse-fragment from the introduction to the 1934 Cuala Press edition of The Words upon the Window-Pane. The aesthetic debates glossed in these references underscore Yeats’s familiarity, and at times disagreements, with the authoritative art writing of Ezra Pound on Brancusi. By revivifying the connections between Pound’s writing on Vorticist sculpture in the 1910s, on Brancusi in the 1920s, and Yeats’s own prose and verse responses to the same works, the chapter complicates a prevailing Vorticist historiography of modernist sculpture. In so doing, the chapter also considers Yeats’s status as a modernist by comparing his writing on modern verse with his writing on modern sculpture, and his selection of poems for the Oxford Book of Modern Verse (1936).
Cities and the Environment on the Constitutional Stage
Authors: Nelson Rebecca
Published: December 2022

Human influence on the environment is now widely considered to be so significant as to constitute a new geological epoch, the Anthropocene. The rapidly accelerating pace, scale, and impact of urbanization makes it a critical driver of that influence, so much so that some prefer the term ‘Astycene’—an era altered and characterized by the ‘astos’, or urban dweller. The widespread adoption of modern constitutional environmental rights provisions speaks to the scale and severity of contemporary environmental threats in general. However, the centrality of cities in causing and experiencing environmental threats, and the corresponding constitutional implications, remain substantively unaddressed by constitutions and their scholars. This chapter applies an environmental lens to the key questions of whether constitutions should recognize cities, and what any such recognition should seek to accomplish. It uses the metaphor of the constitutional stage, first describing the environmental backdrop to that stage in physical and institutional terms. It then argues that although cities can act in the role of both environmental victim and villain, recognizing them in constitutions would help address important environmental problems in both situations. Both situations also support constitutionalizing intergovernmental coordination mechanisms that can adapt to changing circumstances—in other words, action on stage that unfolds using dialogues and improvisation, rather than the ‘constitutional soliloquys’ of exclusive powers and rigid constitutional formulations. Finally, the chapter explores factors relevant to the casting call—determining what counts as a city for the purposes of an environmentally informed constitutional narrative.
The City in the Future of Federalism
Authors: Schragger Richard
Published: December 2022

Cities have been largely absent from the theory and doctrine of federalism, especially in the US, where federalism discourse is invariably preoccupied with states. This chapter first considers the mismatch between cities’ increasing economic, political, and sociological importance and their relative lack of status in constitutional theory. Second, it discusses the use and definition of the term ‘city’—a threshold issue that drives much subsequent theorizing about it. And third, it considers the various ways institutional designers might go about empowering the city. These observations lay the groundwork for the broader argument that state-based federalism is bad for cities. The ‘old’ federalism, based on the theory that sub-national governments are sharply limited in their policy choices by the threat of capital flight, presumed weak and ineffectual cities—a presumption that has become self-fulfilling in the US, where states have been aggressively reducing and restraining city power. A ‘new’ federalism would recognize the central role of cities in an urban-based political and economic order and provide them powers commensurate with that role. As global urbanization continues apace, the urban–rural political divide deepens, and nation-states face repeated crises of legitimacy, the necessity of building the city into our constitutional institutions becomes increasingly apparent.
Constitutional Pluralism as a Descriptive Theory
Authors: Bobić Ana
Published: December 2022

This chapter sets out the descriptive features of constitutional pluralism. It addresses its descriptive elements, first theoretically, and subsequently, offering a broad brush prima facie substantiation of their operation. More specifically, constitutional pluralism is a system in which different claims to ultimate authority run in parallel, regularly engage in conflict, and are resolved incrementally through the operation of the auto-correct function, sustained by the application of sincere cooperation and mutual respect. The analysis shows the recurring use of a shared judicial vocabulary which points to the existence of a common understanding of the division of obligations among the participants of the European judicial space driven by heterarchy. This provides prima facie evidence of the basic descriptive premises of the theory of constitutional pluralism, where the co-existence of multiple claims to ultimate authority drives the relationship between EU and national constitutional law. The interaction of national and EU law demonstrates the existence of in-built conditions for judicial accommodation of conflict (‘the auto-correct function’), such as the principle of EU-friendly interpretation in national constitutional law, or the national identity clause in primary EU law.