bluuebunny/crossref_metadata_2025 huggingface dataset:
533. Protocol for and Efficacy of Monoclonal Antibody (mAb) Treatment of SARS-CoV-2 at a VA Medical Center
Authors: Nguyen Phuong Khanh , Dieringer Thomas D , Greeley Adela , Kun Suny , Calub Feliza , Pham My-Phuong , Graber Christopher J , Goetz Matthew B , Goetz Matthew B , Ikuta Kevin
Published: December 2021

Background

Bamlanivimab and casirivimab/imdevimab were the first monoclonal antibodies (mAb) developed against SARS-CoV-2 and proved beneficial early in the course of infection. However, real-world administration of these therapies presents logistical challenges. We present our experience implementing mAb treatment at a large VA Medical Center and review the efficacy of therapy in preventing hospitalization from COVID-19 in a closed healthcare system.

Methods

All positive outpatient COVID tests performed at VA Greater Los Angeles Healthcare System (GLA) were reviewed by the Emergency Medicine (EM) and Infectious Diseases (ID) Sections for mAb eligibility beginning 12/2/2020. Due to limited supply, treatment was prioritized for patients at highest risk of developing severe disease, as determined by EM/ID with input from a machine learning ensemble risk estimation model produced by VA National Artificial Intelligence Institute (Figure 1). If a patient declined or did not reply, treatment was offered to the next patient on a ranked eligibility list. Those who declined or were eligible but not treated were included in the analysis. Patients were excluded if they were hospitalized before treatment was offered. We collected data on age, comorbidities, date of diagnosis, and admission at 30 days after diagnosis. A multivariate log binomial regression was performed to determine the relative risk of admission within 30 days of diagnosis for those who received mAb therapy as compared to those who did not, adjusting for age and comorbidity. All analysis was done in R (version 4.0.5).

Results

139 patients met inclusion criteria. 45 (32%) received mAb therapy, 48 (35%) declined mAb therapy, and the remaining 46 (33%) either did not respond or were not offered mAb therapy. Hospitalizations following diagnosis in each group are illustrated in Figure 2. There was a trend towards reduced absolute and relative risk of hospitalization (Table 1). There were no anaphylactic events in patients who received mAb therapy.

Conclusion

At our facility, a system for rapid identification of candidates and a coordinated distribution plan was essential in ensuring timely administration of mAb therapy to eligible patients. Administration of mAb showed a trend towards decreased risk of hospitalization due to SARS-CoV-2.

Disclosures

Adela Greeley, MD, Kite (Other Financial or Material Support, My spouse is an employee) Matthew B. Goetz, MD, Nothing to disclose
534. The Use of Tocilizumab and Remdesivir in SARS- CoV-2 Patients in El Paso Texas: A Longitudinal Comparative Observational Study
Authors: Almaghlouth Nouf K , Anyiam Felix , Attia Mohamed , Robinson Matthew , Shah Sidra , Haq Syed , Guevara Roberto , Antony Suresh
Published: December 2021

Background

Currently, the management of SARS-CoV-2 varies with no definitive clinical guidelines, as scientific evidence across the globe differs in therapeutic options. This study intends to provide some clarity to the insufficient data based on the role of monotherapy with tocilizumab (TCZ) and combination therapy with remdesivir (RDV) and TCZ among patients in El Paso, Texas.

Methods

154 SARS-CoV-2-positive patients from four different hospitals in El Paso, Texas, were screened, with 113 eligible for this longitudinal comparative observational study (2/1/2020-10/31/2020). Group 1 (80 patients) were given TCZ within the first 24 hours of hospitalization, followed by methylprednisolone for 72 hours, and Group 2 (33 patients) received TCZ as detailed in the single therapy group, plus RDV within the first 24 hours. Mann Whitney U test assessed Median differences in laboratory biomarkers and Bivariate Logistic Regression assessed the odds of risk. An observation is said to be statistically significant if P-value is ≤ 0.05.

Results

A statistically significant increased median IL-6 values were noted among those given only TCZ compared to those that received TCZ plus RDV (511.33 vs. 199.0) with a P-value (0.007). Patients in Group 1 had statistically significant lower odds for ventilation use than Group 2 (OR=0.34, 95%CI=0.12-0.95, p=0.034), although no statistically significant difference in mortality outcomes was observed across groups (OR=0.43, 95%CI:0.13-1.39, p=0.269).

Table 1. Laboratory biomarkers and treatment groups (Mann Whitney U test)

Table 2. Clinical outcomes and treatment groups using the Bivariate Logistic regression (OR)

Conclusion

This study population is unique as it reflects a predominantly Hispanic demographic population in El Paso with different genetics, background characteristics, and predisposition to diabetes, and obesity than the rest of the United States (US). We concluded that the use of TCZ in SARS-CoV-2 positive patients in El Paso, with or without RDV, reported no mortality benefit. However, some minimal/non-use of ventilation benefit was observed in Group 1. Our study design is considered the first of its kind using TCZ and RDV in a longitudinal comparative observational study. Nonetheless, a randomized controlled trial study is recommended to ultimately determine the combination role of TCZ and RDV among this highly vulnerable group of patients.

Disclosures

All Authors: No reported disclosures
535. Comparison of Outcomes in Patients Positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection After Monoclonal Antibody Therapy (MAT) with Bamlamivimab or Casirivimab-Imdevimab
Authors: Nichols Courtney , Lustberg Mark , Sobhanie Mohammad Mahdee , Lehman Joy , Reed Erica E , Kman Nicholas E , Conroy Mark , Dick Michael , Allen James N , Parsons Jonathan , Malvestutto Carlos
Published: December 2021

Background

Limited options currently exist for treatment of patients diagnosed with symptomatic coronavirus 2019 (COVID-19). Monoclonal antibody therapy (MAT) has been investigated as a therapeutic option for symptomatic COVID-19 patients in the outpatient setting at high-risk for progression to severe disease based on emergency use authorization (EUA) criteria. No published studies have compared outcomes for patients treated with different MAT for COVID-19.

Methods

This was a single-center, retrospective cohort study at The Ohio State University Wexner Medical Center to compare COVID-19-related emergency room (ER) visits, admissions, and mortality at 30 days after MAT infusion for adult patients with symptomatic SARS-CoV-2 between November 16, 2020 and February 2, 2021 who received bamlanivimab versus those who received casirivimab-imdevimab. Statistical analysis used logistic regression analysis to determine the odds ratio (OR) to evaluate the relationship between patient characteristics, MAT, and outcomes.

Results

The cohort included 943 patients with SARS-CoV-2 who received MAT, including 658 patients who received bamlanivimab and 285 who received casirivimab-imdevimab. Outcome results between patients who received bamlanivimab and casirivimab-imdevimab showed no statistically significant difference seen in the number of COVID-19 related ER visits (3.2% vs 3.5%, p = 0.80), hospital admissions (4.6% vs 2.8%, p = 0.21), or mortality (0.5% vs 0.7%, p = 0.63). Multivariate analysis showed no statistically significant difference in outcomes between the groups when accounting for potential confounders. As reflected in the Table, chronic lymphocytic leukemia (CLL), gender, and asthma were associated with increased COVID-19 related ER visit within 30 days of infusion and age, chronic obstructive pulmonary disease, CLL, and lupus were associated with increased risk for COVID-19 related admission within 30 days of infusion. Age and obesity with body mass index greater than 35 mg/kg2 were associated with increased risk for COVID-19 related mortality at 30 days.

Conclusion

COVID-19 related outcomes were similar when comparing patients with COVID-19 treated with bamlanivimab versus those treated with casirivimab-imdevimab.

Disclosures

Mohammad Mahdee Sobhanie, M.D., Regeneron (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator, Was a sub-investigator for Regeneron 2066 and 2069) Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)
537. Implementation of a Workflow for COVID-19 Monoclonal Antibody Infusions at a Veterans Affairs Medical Center
Authors: Patel Pratish C , Adenew Ayne , McKnight Angela , Jeng Kevin , Liappis Angelike P
Published: December 2021

Background

In the setting of the global pandemic due to COVID-19, high-risk patients with mild to moderate disease were identified as a group who would benefit from COVID-19 monoclonal antibody (mAB) treatment to mitigate progression to severe disease or hospitalization. The U.S. Food and Drug Administration (FDA), under Emergency Use Authorizations (EUA) approved multiple COVID-19 mAB therapies with specific criteria for eligibility of candidates, documentation of discussion with patients, and reporting of all errors and serious adverse events.

Methods

A cross discipline working group implemented a mAB clinic at complexity level 1a VA Medical Center in metropolitan Washington, D.C. through collaboration of personnel committed to patient care. The team successfully persuaded hospital leadership to provide space and leveraged technologies for rapid communication and dissemination of education. A stewardship driven medical center wide surveillance system rapidly identified outpatients for screening; primary care and ED providers were engaged through various electronic methods of education, including email, web-based team communication, intranet webpages and other electronic modalities. Within the EMR, an order panel was implemented to assure that the key requirements of the EUA were met and the provider was guided to the appropriate mAB, nursing, and PRN rescue medication orders.

Results

Of over 17,000 COVID-PCR tests were performed at our medical center, 198 outpatients were screened and 16 received COVID-19 mAB infusions between January 2, 2021 to May 31, 2021. One patient experienced a reaction requiring the infusion to be stopped and supportive medications to be administered; there were no long-term sequalae reported as a result of this event.

Conclusion

A multidisciplinary collaboration is well suited to implement innovative processes and policies for novel therapies in the middle of a pandemic. An agile workflow, regular communications between members of the workgroup, and commitment of institutional leadership helped facilitate the changes necessary to provide our patients the opportunity to receive potentially life-saving therapies.

Disclosures

All Authors: No reported disclosures
539. Impact of Corticosteroids when Combined with Tocilizumab or Remdesivir for the Treatment of Severe SARS-CoV-2
Authors: Rosati Michael , Vyas Nikunj M , Hou Cindy
Published: December 2021

Background

Tocilizumab (TCZ) and remdesivir (RDV) have both shown benefit for patients with SARS-CoV-2. However, there have been no head to head studies comparing the efficacy of the two therapies. The purpose of this study is to compare clinical outcomes of patients who have received corticosteroids (CS) along with TCZ or RDV.

Methods

This is an IRB approved retrospective observational study completed in a three hospital health system in New Jersey. Patients were included if age was ≥ 18, admitted with SARS-CoV2 infection requiring oxygen. Patients were stratified into two treatment arms; CS + TCZ and CS + RDV. The primary objective was to compare all-cause inpatient mortality (ACIM) based on oxygenation status; nasal cannula (NC), high-flow nasal cannula (HFNC), and invasive mechanical intubation (IMV). Secondary objectives was a snapshot analysis with a focus on clinical improvement (CI) defined as improvement in clinical ordinal scale by 2 or more at end of stay. Additional endpoint included progression to IMV after therapy initiation.

Results

There were total of 1053 patients included (123 in the CS+TCZ arm, 930 in the CS+RDV arm). Oxygen requirements were as follows: In the CS+TCZ arm (NC n=57, HFNC n=26, IMV n=40), and the RD+CS arm (NC n=669, HFN n=159, and IMV n=102). Results from the primary endpoints can be found in Table 1. No statistically significant differences were observed between the two treatment arms. For the secondary objective there were 214 patients included (70 in the CS+TCZ arm and 105 in the CS+RDV arm). For patients receiving NC, no difference seen in CI between two treatment arms (81.4% CS+RDV vs. 81.5% CS+TCZ). In HFNC group more patients in the CS+TCZ group observed CI compared to CS+RDV (68.8% vs. 40%). Less patients requiring HFNC progressed to IMV in CS+TCZ group (25%) compared to CS+RDV (40%).

Conclusion

No statistical difference in ACIM was detected between the two treatment arms regardless of baseline oxygenation requirements. There was a trend towards lower ACIM for IMV patients in the CS+TCZ arm compared to the CS+RDV arm. More patients experienced CI in CS+TCZ group compared to CS+RDV in HFNC group. Less HFNC patients also required new IMV in the CS+TCZ arm. Larger studies need to be performed to evaluate a true statistical difference between the two treatment arms.

Disclosures

All Authors: No reported disclosures
540. Does Remdesivir Impact the Clinical Outcome of Patients with COVID 19 Infection?
Authors: Gunasekaran Karthik , John Jisha S , Alexander Hanna , Gracelin Naveena , Samuel Prasanna , Rupali Priscilla
Published: December 2021

Background

Remdesivir (RDV), was included for the treatment of mild to moderate COVID-19 since July 2020 in our institution, following the initial results from ACTT-1 interim analysis report. With the adoption of RDV, there seems to be anecdotal evidence of efficacy as evidenced by early fever defervescence, quick recovery when on oxygen with decreased need for ventilation and ICU care. We aimed to study the impact of RDV on clinical outcomes among patients with moderate to severe COVID –19.

Methods

Nested case control study in the cohort of consecutive patients with moderate to severe COVID – 19. Cases were patients initiated on RDV and age and sex- matched controls who did not receive RDV were included. The primary outcome was in-hospital mortality. Secondary outcomes were, duration of hospital stay, need for ICU, duration of oxygen therapy and need for ventilation.

Results

A total of 926 consecutive patients with COVID – 19 were included, among which 411 patients were cases and 515 controls. The mean age of the cohort was 57.05±13.5 years, with male preponderance (75.92%). The overall in-hospital mortality was 22.46%(n=208). On comparison between cases and controls there was no statistically significant difference with respect to primary outcome [22.54% vs. 20.78%, (p value: 0.17)]. Progression to non-invasive ventilation (NIV) was higher among the controls [24.09% vs. 40.78% (p value: < 0.001*)]. Progression to invasive ventilation was also higher among the controls [5.35% vs. 9.71% (p value: 0.014*)]. In subgroup analysis among critically ill patients, the use of RDV showed decrease in mortality (OR 0.32 95% CI; 0.13 – 0.75 p value – 0.009*).

Conclusion

RDV did not decrease the in-hospital mortality among moderate to severe COVID – 19. However, there seems to be a significant reduction in mortality in critically ill patients.

Disclosures

All Authors: No reported disclosures
541. Comparing Patients with Severe COVID-19 Who Improve to the Point of Discharge Following an Abbreviated Course (< 5 Days) of Remdesivir (RDV) Versus a Standard Course (≥5 Days)
Authors: Pham Huan , Chen Qiaoling , Li Aldon , Baghban Adam , Cheruvanky Anita , Faiad Graciela
Published: December 2021

Background

The COVID-19 pandemic has negatively affected our healthcare system. Our hospitals have reached maximum capacity on several occasions. Because of the need to make beds available to new patients, some patients with severe COVID-19 who were on low flow O2 supplementation have been discharged home prior to completion of the standard (≥ 5-day) RDV course. To date, data are limited regarding clinical outcomes on these patients. Because of this, we conducted a retrospective study to assess the clinical outcomes of patients who received an abbreviated treatment course of RDV.

Methods

Retrospective (chart review) study

Subject population

All nonpregnant adult patients who were hospitalized at Kaiser Permanente Riverside Medical Center and Kaiser Permanente Moreno Valley Medical Center in 2020 with severe COVID-19 who required low flow O2 supplement during hospitalization who received RDV and discharged from hospital alive. Severe COVID-19 = positive SARS-CoV-2 PCR + evidence of lung involvement on lung imaging (X-ray or CT) + O2 saturation ≤ 94% on room air or requirement of O2 supplement.

Inclusion criteria

Age ≥ 18 years; Hospitalized with severe COVID-19; Given RDV

Exclusion criteria

Pregnancy; O2 requirement > 6 L including high flow and mechanical ventilation (noninvasive or invasive); discontinuation of RDV due to adverse effects

Figure 1. Patient Section.

Results

Mortality rate: no difference (2.1% vs 1.8%, p=0.84). 30 day post-discharge ED visit: twice more likely in the abbreviated RDV group as compared to the group receiving the standard duration (16.1% vs 8.5%, p=0.03). 30 day readmission: almost 10 times more likely in the abbreviated RDV group as compared to the group receiving the standard duration (11.9% vs 1.2%, p=< 0.001).

Table 1. Patient's Characteristics

Table 2. Clinical Outcomes. *8 Patients Who Died Within 30-Day from Discharge Were Excluded

Conclusion

Though there is no difference in 30 day mortality rate, the patients who received the abbreviated RDV course are twice more likely to have ER visit and 10 times more likely to have readmission within 30 day post discharge despite more patients in the abbreviated course receiving steroids. The findings suggest that completing an at least 5-day course of RDV may be beneficial even in patients who demonstrate a clinical response earlier in course.

Disclosures

All Authors: No reported disclosures
542. Use of Bamlanivimab in Cancer Patients with Mild-to-Moderate COVID-19
Authors: Brock Patricia , Dagher Hiba , Wechsler Adriana H , Lipe Demis N , Chaftari Patrick , Chaftari Anne-Marie , Gaeta Maria S , Johnson Tami N , Coussirat Daniel J , Aitken Samuel L , Aitken Samuel L , Jiang Ying , Malek Alexandre , Hachem Ray Y , Raad Issam I
Published: December 2021

Background

Bamlanivimab is a monoclonal antibody that was granted an emergency use authorization by the US Food and Drug Administration in November 2020 for patients with mild to moderate coronavirus disease 2019 (COVID-19). It initially showed promising results with decreasing hospitalizations and return emergency department visits in immunocompetent patients. We evaluated the role of bamlanivimab in the cancer patient population.

Methods

We conducted a retrospective matched study of all cancer patients diagnosed with mild to moderate COVID-19 who received bamlanivimab in our acute cancer care center (ACCC) from December 2020 to February 2021. These patients were compared to a control group of cancer patients who presented to our ACCC and were diagnosed with mild to moderate COVID-19 from March to November 2020 before the introduction of bamlanivimab. Control patients were matched by age and underlying malignancy. All patients had a baseline oxygen saturation ≥ 94% and an absolute neutrophil count > 500 mm3. Demographics, clinical characteristics, and outcome that included COVID-related admissions, oxygen desaturation, ICU admission and 30-day mortality were compared in both groups.

Results

A total of 108 patients were analyzed with 54 patients in each group, of which 59% consisted of hematologic malignancies, and 33% were ≥ 65 years. The presenting symptoms were similar in both groups and mainly consisted of cough, fever, and dyspnea. Patients who received bamlanivimab were less likely to be admitted to the hospital (24% vs. 91%; p< 0.0001), experience oxygen desaturation < 94% during follow-up (11% vs 44%; p=0.0001), require oxygen supplement (7% vs. 44%; p< 0.0001), or be admitted to the ICU (4% vs 15%; p=0.046). No 30-day mortality was observed in the bamlanivimab group with 2 (4%) occurring in the control group. However, the difference was not significant.

Conclusion

Bamlanivimab decreased hospital and ICU admissions in cancer patients. In addition, bamlanivimab reduced oxygen requirement and the risk of hypoxia and progression to severe disease in this patient population.

Disclosures

Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support
545. A Retrospective Review of 30-day Mortalities in Solid-Organ Transplant Recipients (SOT) versus Non-Transplant Patients (NTP) Receiving Remdesivir (REM) and Dexamethasone (DEX) for COVID-19 Pneumonia
Authors: Vyas Krina , Epps Kevin L , Zhang Nan , Shah Sadia , Soto-Arenall Matthew , Brumble Lisa , Libertin Claudia R
Published: December 2021

Background

Treating COVID-19 infection in SOT is challenging due to long-term use of immunosuppressive agents. REM is the only FDA-approved anti-viral for SARS-COV-2 infection. DEX showed decrease in mortality in the Recovery Trial. COVID-19 treatment guidelines for SOT patients are the same as NTP despite limited literature on those outcomes. Our primary objective was to determine if 30-day mortality was different between SOT and NTP matched cohorts using these 2 drugs. The secondary objectives included comparisons of length of stay (LOS), days on mechanical ventilation (DMV), and the use of other treatment modalities.

Methods

We retrospectively collected data for hospitalized SOT and NTP, 18 years and older, with pcr-confirmed SARS-CoV-2 infection receiving REM and DEX from May 1, 2020, to October 10, 2020, at Mayo Clinic Florida. IRB approval was obtained. Descriptive statistics were used to analyze the data. Continuous variables were summarized as mean (standard deviation) or median (range) where appropriate, while categorical variables were reported as frequency (percentage).

Results

Of 80 patients who met the inclusion criteria, 28 were SOT, and 52 were NTP. The SOT cohort was subcategorized below:

SOT patients were significantly younger than NTP (p < .001). Further, SOT patients had significantly longer LOS (p = 0.043) and more COVID-19 modalities (75% vs. 36.5%, p = 0.002) compared to NTP. Among the 28 SOT patients, 2 of them died within 30 days of admission, and among the 52 NTP patients, 7 of them died within 30 days. The 30-d survival estimate for SOT group is 92.9% (95% CI: 83.8% - 100.0%) and for NTP group is 86.5% (95% CI: 77.7% - 96.3%). The log-rank test was not significant between the groups (p=0.37), but the NTP has a worse survival curve from the figure below.

SOT-NTP Survival Curve

Conclusion

SOT group was younger, had longer LOS, and more COVID-related modalities. The 30-d survival estimate for SOT group is 92.9% and for NTP group is 86.5%, but the survival curve for NTP was worse likely secondary to age. Use of REM & DEX in SOT recipients is a valid recommendation.

Disclosures

Claudia R. Libertin, MD, Gilead (Grant/Research Support)
547. Risk Factors Associated with 30-Day Mortality in a Large Cohort of Patients who Received Remdesivir and Corticosteroids for Severe COVID-19
Authors: Gupta Kartik , Monday Lea , Kaushik Milan , Alangaden George J , Brar Indira
Published: December 2021

Background

Remdesivir (RDV), an antiviral agent, is approved by Food and Drug Administration (FDA) for the treatment of patients (pts) admitted with SARS-COV-2 infection (COVID-19). Earlier RDV studies (such as ACCT-1) prior to widespread use of corticosteroids (CS), showed a 30-day mortality of 11%. Advanced age, obesity, and certain comorbidities are known risk factors for death in COVID-19, but whether these risks vary in pts treated with RDV and CS is unknown. As of March 20, 2020 CS were routinely used for the treatment of pts admitted with COVID19 in our health care system. The objective of this study was to identify risk factors associated with 30 -Day mortality in a cohort of pts admitted with COVID-19 and who received RDV and CS.

Methods

This retrospective cohort study evaluated pts admitted to a health system in South East Michigan with COVID-19 between March and November 2020 who received ≥1 dose RDV. Demographics, comorbidities, and characteristics including quick sequential organ failure assessment (qSOFA) score were collected and compared between patients who died versus survived. Primary outcome was 30 day mortality. Secondary outcomes were risk factors for death using logistic regression and time-to-event analysis.

Results

A total of 1,591 pts received RDV and were included in the study; median age 67 years, 56% male and 18% Black. RDV use increased after emergency use authorization and FDA approval (Fig 1). Death within 30 days occurred in 15.3%. Patients who died were older males with higher rates of hypertension, kidney disease, diabetes, and were more likely to have qSOFA ≥2 on arrival (Table 1). In a multivariable logistic model, advanced age, male gender, pulmonary disease, CKD, obesity, and qSOFA≥2 were independent predictors of death (Figure 2). Among these, age and qSOFA≥2 were the most important risk factors (Figure 2).

Patients receiving remdesivir (red) were included in the study. Routine use of corticosteroids was adopted on all patients in our health system beginning March 20, 2020. System-wide use of remdesivir increased following Food and Drug Administration approval in fall 2020.

On both logistic regression and time-to-event analysis, advanced age and qSOFA ≥ 2 had the highest predictive value for mortality. Others comorbidities were similar and comparable in importance.

Conclusion

The population in our Real-world study was older with more comorbidities as compared to ACCT-1, and the 30 day mortality was 15%. Despite the use of CS and RDV advanced age and qSOFA were the most important drivers of mortality. Future, therapeutic strategies need to focus on this group which is at the highest risk of dying from COVID-19 infection.

Disclosures

All Authors: No reported disclosures
548. Convalescent Plasma in Hospitalized Pediatric and Obstetric patients with COVID-19
Authors: Ikeda Saki , Benzi Eduardo , Hensch Lisa , Devaraj Sridevi , Hui Shiu-Ki Rocky , Gandhi Manisha , Fox Karin , Teruya Jun , Munoz Flor M
Published: December 2021

Background

Published data on COVID-19 convalescent plasma (CCP) use in children and obstetric patients is limited. We describe a single-center experience of hospitalized patients who received CCP for acute COVID-19.

Methods

We performed a retrospective review of children 0-18-years-old and pregnant patients hospitalized with laboratory-confirmed acute COVID-19 who received CCP from March 1st, 2020 to March 1st, 2021. Clinical and laboratory data were collected to assess the safety of CCP administration. Antibodies to SARS-CoV-2 were measured before and at various timepoints post CCP transfusion. Correlation between SARS-CoV-2 immunoglobulin administered versus the SARS-CoV-2 anti-Spike immunoglobulin response in patient serum was assessed.

Results

Twenty-two children and 10 obstetric patients were eligible. 12 pediatric and 8 obstetric patients had moderate disease and 10 pediatric and 2 obstetric patients had severe disease. 5 pediatric patients died. 18/37 (48.6%) CCP units that were measured met FDA criteria for a high IgG titer. There were no complications with transfusion based on CDC, NHSN Biovigilance Component: Hemovigilance Module Surveillance Protocol. Two pediatric patients had fevers a few hours after CCP with low suspicion for a transfusion reaction. Median SARS-CoV-2 anti-spike antibody levels of pediatric patients post-transfusion for 0-7 days was 80.6AU/mL (range: 2-1070), 8-21 days was 180AU/mL (range: 12-661) and >21 days was 210AU/mL (range: 4.1-1220). For obstetric patients, post-transfusion antibody levels were only obtained 0-7 days post-transfusion with median 45AU/mL (range: 9.5-100). High-titer CCP showed a positive correlation with rise in patient immunoglobulin levels only in the obstetric patients but not in pediatric patients.

Conclusion

CCP was administered safely to our moderately to severely ill pediatric and obstetric patients. Among pediatric patients, the median serum antibody level increased over time after transfusion and suggested that CCP did not interfere with the endogenous antibody production. Antibody dose of high-titer CCP correlated with post-transfusion response in only obstetric patients. Randomized trials in pediatric and obstetric patients are needed to further understand how to dose CCP and evaluate efficacy.

Disclosures

Jun Teruya, MD, PhD, Apelo Consulting Pvt. Ltd (Consultant)Hemosonics (Other Financial or Material Support, Honorarium) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)
549. Monoclonal Antibody Therapy for COVID-19 Infection in Michigan: The Flint Experience
Authors: Younas Mariam , Osterholzer Danielle , Flues Brandon R , Rios-Bedoya Carlos , McDonald Philip , Bachuwa Ghassan , Tupper Michael W , Jaggi Michael
Published: December 2021

Background

Bamlanivimab (BAM), a neutralizing IgG1 monoclonal antibody (mAb), received emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA) for treatment of mild to moderate COVID-19 infection in patients 12 years of age and older weighing at least 40 kg at high risk for progressive and severe disease on Nov 10, 2020. The purpose of this study is to describe our experience with this treatment modality.

Methods

Hurley Medical Center (HMC), is a 443-bed inner city teaching hospital in Flint, MI. HMC administered its first BAM infusion on Nov 19, 2020. Through April 30, 2021, 407 patients with confirmed SARS-CoV-2 infection, received a mAb infusion. 62/407 patients received the combination mAb therapy of BAM + Etesevimab, as the EUA for BAM monotherapy was revoked on 04/16/21. We retrospectively collected basic demographic data and hospitalization to our facility within 14 days of receiving mAb therapy on these patients.

Results

During the 5.5 month study period, patients receiving mAb therapy at HMC had a mean age of 56 years (yrs) (± standard deviation) (± 15.4) and a mean Body Mass Index (BMI) of 34 kg/m² (± 8.5) (Tables 1,2). African Americans (AA) comprised 48% (194/407) (Table 3) and females comprised 54% (220/407) of the cohort. 6% (25/407) of the patients required hospitalization within 14 days of mAb infusion, had a mean age of 58 yrs (± 17) (p-value 0.62) and a mean BMI of 32 kg/m² (± 9) (p-value 0.33). Females and AA comprised 56% (14/25) and 48% (12/25) of this subgroup respectively (p-value 1.0). No deaths were reported within 30 days of infusion in this cohort.

Conclusion

Previously published reports cite a hospitalization rate in untreated high-risk COVID-19 infected patients of 9-15%. During the period of study, the county hospitalization rate and county mortality rate for all comers with COVID-19 was 6.6% and 2.7% respectively while our high risk cohort had a hospitalization rate of 6% and with no deaths reported. Our cohort had much lower rates of hospitalization and death than would be expected especially in a group which comprised of 48% AA in an underserved area. mAb therapy seems to have a protective effect with significant reduction in the hospitalization and mortality rate among high-risk patients with COVID-19 infection and should be prioritized for administration.

Disclosures

All Authors: No reported disclosures
550. Bamlanivimab and Casirivimab/Imdevimab Treatment Outcomes: Results from a Large Healthcare System’s Structured Implementation Experience
Authors: Polk Christopher , Jacobs Anna , Sampson Mindy , Leonard Michael , Medaris Leigh Ann , Branner Christopher , Goel Vineet , Davidson Lisa
Published: December 2021

Background

Neutralizing antibody therapies targeting SARS-CoV-2 have been released for emergency use authorization by the FDA. Little is published on their real-world experience. In this retrospective study we share the results of our early experience on patient outcomes from use of these neutralizing antibodies within a large healthcare system.

Methods

We retrospectively analyzed results of a healthcare system wide program to pro-actively identify and treat COVID-19 patients with neutralizing antibody therapy.

Results

The 449 patients identified for SARS-CoV-2 neutralizing antibody therapy during the study period were retrospectively classified as falling in one of the three groups: untreated (199), bamlanivimab (87) and casirivimab/indevimab (125) treated patients (Table 1). Reasons identified patients were not treated most commonly were patient declined (n=74), unable to be contacted (n=36), out of treatment window (n=23), asymptomatic and feeling better (n=21) or did not have transportation (n=9). Bamlanivimab infusion did not reduce emergency room (ER) visits or hospitalization compared to untreated patient within 30-days of follow up (Table 2), and among all patients treated with antibody therapy only treatment with bamlanivimab and non-white race were predictors of need for hospitalization (Table 3). Casirivimab/indevimab did reduce subsequent ER visits or hospitalization within 30 days post-infusion when compared to the untreated group. However, patients treated with either antibody therapy had lower acuity of COVID-19 disease as reflected in need for intensive care unit (ICU) stay, mechanical ventilation or death (Table 2).

Table 1. Characteristics of infused vs uninfused patients

Table 2. Outcomes in treated vs untreated patients

Table 3. Risk factors for ED visits or hospitalization in infused patients

Conclusion

Either neutralizing antibody therapy appears to markedly reduce acuity of COVID-19 disease even if patients do progress to requiring hospitalization. However, casirivimab/indevimab therapy also decreased ER visits and hospitalization suggesting better efficacy in our experience.

Disclosures

Christopher Polk, MD, Atea (Research Grant or Support)Gilead (Advisor or Review Panel member, Research Grant or Support)Humanigen (Research Grant or Support)Regeneron (Research Grant or Support) Mindy Sampson, MD, Regeneron (Grant/Research Support)
553. Outcomes in Patients Positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection After Treatment with Monoclonal Antibody Therapy (MAT) in the Outpatient Setting
Authors: Nichols Courtney , Lustberg Mark , Sobhanie Mohammad Mahdee , Lehman Joy , Reed Erica E , Kman Nicholas E , Conroy Mark , Dick Michael , Allen James N , Parsons Jonathan , Malvestutto Carlos
Published: December 2021

Background

Monoclonal antibody therapy (MAT) was granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration for treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults with positive SARS-CoV-2 viral testing and at high risk for progression to severe COVID-19 with up to 10 days of symptoms. This study assessed the impact of MAT on COVID-19-related ER visits, admissions, and mortality for patients diagnosed with COVID-19.

Methods

This was a single-center, retrospective study at The Ohio State University Wexner Medical Center to compare COVID-19-related ER visits, admissions, and mortality at 30 days after receiving MAT in the outpatient setting with either bamlanivimab or casirivimab-imdevimab in adult patients diagnosed with SARS-CoV-2 between November 16, 2020 and February 2, 2021. Outcomes in patients who received MAT were compared to those of a control group of patients diagnosed with COVID-19 in the outpatient setting from May 16, 2020 through November 15, 2020 who would have qualified for MAT through EUA criteria had it been available. Statistical analysis used logistic regression analysis with backward selection to determine the odds ratios (OR) and the 95% confidence interval to evaluate the relationship between patient clinical characteristics and outcomes.

Results

This study cohort included 1,944 patients, including 943 who received MAT and 1,001 in the control group. The MAT group included 658 who received bamlanivimab and 285 who received casirivimab-imdevimab. Patients who received MAT compared to the control group had a lower rate of COVID-19 related ER visits (3.3% vs 7.4%, p = < 0.0001) and hospital admissions (4.0% vs 7.8%, p = < 0.0001). No statistically significant difference was seen in mortality between the MAT group (0.5%) and control group (1.1%, p = 0.17). After accounting for potential confounders, the difference between the monoclonal antibody and control groups remained significant for ER visits and hospital admissions as reflected in the table.

Conclusion

Patients who received MAT for COVID-19 in the outpatient setting had a lower rate of COVID-19-related 30 day ER visits and hospitalizations compared to those who did not receive MAT, adjusting for potential confounders.

Disclosures

Mohammad Mahdee Sobhanie, M.D., Regeneron (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator, Was a sub-investigator for Regeneron 2066 and 2069) Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)
554. Clinical Impact of Monoclonal Antibody Therapy with SARS-CoV-2 Infection
Authors: Mann Inderjit , Monteforte Melinda , Go Roderick
Published: December 2021

Background

The novel coronavirus SARS-CoV2 is the causative agent for COVID-19 responsible for the ongoing global pandemic. The spike protein on its surface binds to the angiotensin-converting enzyme 2 receptor helps to enter human cells. Neutralizing antibodies to this protein can be protective and helpful in alleviating symptoms. Monoclonal antibodies (mAb) have been utilized in the U.S. under an emergency use authorization by the FDA, including bamlanivimab (BAM) and casirivimab-imdevimab (CAR/IMD). We report our experience of using COVID mAb.

Methods

We conducted a retrospective chart review of patients that received CAR/IMD or BAM between December 1st, 2020, and May 15th, 2021. Medical records were reviewed to determine demographic and clinical information as well as tolerability and effectiveness of mAb.

Results

463 patients with mild to moderate symptoms of SARS-CoV2 received mAb: 355(176 Men) BAM, 108(53 Men) CAR/IMD. The median BMI was 31 (17.4 to 62.5), 85% Caucasian, 4% Asian, 3% African American, 4% Hispanic, 4% others. The average duration of symptoms was 3.4 days and included cough (74%), malaise (71%), Headache (28%), dyspnea (28%), rhinorrhea (25%), fever (20%), diarrhea (18%), and anosmia (14%). Risk factors included hypertension (65%), diabetes mellitus (32%), coronary artery disease (22%), asthma (16%), COPD (9%), CHF (9%), CKD (8%), active malignancy (6%), and immunocompromised state (7%). Those who received BAM were older (p=0.000) and have underlying dementia and congestive heart failure (p=0.025 and 0.034, respectively). 27 patients (2 CAR/IMG, 25 BAM) got admitted to the hospital due to worsening of their respiratory status and were treated for COVID-19. 4 patients in the BAM group and 0 in the CAR/IMD group died. 2 patients developed a mild allergic reaction to CAR/IMD, no other side effects were reported in both groups. 37 patients (19 CAR/IMD, 18 BAM) received mRNA COVID vaccine prior. Overall mortality rate was 0.8%. There was no significant difference between BAM and CAR/IMR in terms of hospitalization (p= 0.104) or mortality (p=0.268).

Conclusion

Treatment with BAM versus CAR/IMR was well tolerated and resulted in similar outcomes in terms of hospitalization or mortality.

Disclosures

All Authors: No reported disclosures
555. Utilization of Remdesivir for COVID-19 in the National Veterans Affairs Healthcare System
Authors: Caffrey Aisling , Xin Liao J , Lopes Vrishali
Published: December 2021

Background

As remdesivir (GS-5734) has become a leading treatment for COVID-19, we sought to assess remdesivir utilization patterns, including utilization of concomitant and supportive therapies, and heterogeneity in treatment approaches.

Methods

Our retrospective cohort study included hospitalized Veterans with positive COVID-19 PCR tests treated with remdesivir, from 03/2020 through 4/2021. Using exposure mapping of barcode medication administration records and medication dispensings, we assessed other medications received by each patient on each day of remdesivir treatment. Heterogeneity was defined as patterns of treatment (drug & duration) not shared by any other patient.

Results

Our study included 13,665 patients with COVID-19 receiving remdesivir. The median time to remdesivir initiation from either positive test or hospital admission was 1 day (interquartile range [IQR] 0-4 and 0-1, respectively). The median duration of remdesivir treatment was 5 days (IQR 4-5 days). Median length of hospital stay was 7 days (IQR 4-13). Inpatient mortality was 13.9% and an additional 6.2% of patients died within 90 days of discharge. The most common concomitant and supportive therapies were anticoagulants/antiplatelets (94.8%; enoxaparin 72.6%, heparin 18.4%, apixaban 10.8%, clopidogrel 6.3%), corticosteroids (90.8%; dexamethasone 87.3%, prednisone 2.9%, methylprednisolone 5.5%), statins (55.8%; atorvastatin 38.2%, simvastatin 7.1%, rosuvastatin 6.0%), antibiotics (41.9%; azithromycin 25.6%, ceftriaxone 13.2%, doxycycline 6.0%, vancomycin 4.9%), angiotensin receptor blockers (11.9%) and angiotensin-converting enzyme inhibitors (20.4%), melatonin (29.7%), and aspirin (35.6%). Concomitant utilization of Janus kinase inhibitors (0.5%), interleukin-6 inhibitors (2.4%), and hydroxychloroquine (0.5%) was low. Heterogeneity in concomitant and supportive therapies during remdesivir treatment was 84.6% (68.3% when assessed as drug class/category).

Conclusion

Among hospitalized patients with COVID-19 in the national VA Healthcare system receiving remdesivir, remdesivir was initiated early in the admission and substantial heterogeneity was observed in concomitant and supportive therapies during remdesivir treatment.

Disclosures

Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi, Inc (Research Grant or Support)
558. Implementation and Outcomes of a COVID-19 Monoclonal Antibody Treatment Program in an Urban Safety-net Community Hospital
Authors: Mena Lora Alfredo J , Echeverria Stephanie L , Herald Fischer , McSweeney James , Gumasana Harshil , Burgos Rodrigo M , Borgetti Scott
Published: December 2021

Background

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

Methods

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

Results

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

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

Distribution of patients who received mAB infusions by indication

Conclusion

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

Disclosures

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

Background

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

Methods

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

Results

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

Conclusion

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

Disclosures

All Authors: No reported disclosures