Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19.

BACKGROUND: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD). METHODS: In this phase I/II/III, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus. RESULTS: 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met: in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% CI, -0.51 to -0.05; P = .0172). The primary clinical analysis of death or mechanical ventilation (death/MV) from day 6-29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2-74.0). No safety concerns were noted. CONCLUSIONS: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients.

Exploring Differences, Not Deficits, in Adults with Intellectual and Developmental Disabilities and Serious Illness (TH126A)

Outcomes: 1. Develop an understanding of intellectual and developmental disabilities and explore how an interdisciplinary approach improves palliative care needs for people with intellectual and developmental disabilities 2. Identify strategies for improving palliative and end-of-life care for people with intellectual and developmental disabilities and their families and caregivers It is estimated that 7.4 million individuals living with intellectual and/or developmental disabilities (IDD) reside in the United States. Despite persistent health disparities in accessing preventative care services, people with IDD are living longer and experiencing serious illnesses consistent with the general population, including cancer and heart disease. Yet, many face disproportionate barriers in accessing quality palliative and end-of-life care. The reality of unconscious bias and discrimination has persistent impacts on the health care provided to this population. Research demonstrates that many clinicians perceive people with significant disabilities as having a worse quality of life than non-disabled people due to the presence of a disability. The coronavirus pandemic exacerbated existing societal inequities disproportionately impacting people with intellectual disabilities. IDD has been identified as the strongest independent risk factor for contracting COVID-19 and is second only to age for mortality risk. Many healthcare professionals report feeling unqualified to meet the care needs of the person with IDD adequately. This presentation will introduce the learner to best practices for providing care to people with intellectual disabilities and their families. This interdisciplinary panel of palliative care, hospice, and disability experts will use a blended case study to describe the barriers, facilitators, and best practice approaches for providing quality palliative and end-of-life care for people with IDD. Learners will be provided with actionable steps and tangible resources to partner with people with IDD and disability experts.

Starting the Conversation: Early Initiation of Goals of Care (GOC) May Reduce Inpatient Mortality (SA305C)

Outcomes: 1. Apply Plan-Do-Study-Act methodology to perform quality improvement 2. Analyze and identify improvement opportunities for quality improvement Overview Reducing preventable patient deaths has long been at the center of patient safety efforts. But when patients nearing the end of life are admitted, some well-intended providers may offer non-beneficial treatments that may hasten death or prolong the dying process, result in patient harms, create more suffering, and cause moral injury to families and providers. Non-beneficial care may also negatively affect hospital operations. The COVID-19 pandemic severely disrupted exiting patient safety and resulted in higher-than-normal risk-adjusted mortality. Methods The primary goal was to reduce the risk-adjusted inpatient mortality to < 0.9. This project aimed to reduce in-hospital inpatient mortality by increasing discharges of hospice-appropriate patients to hospice. The study population included all adult patients admitted under the Medicine service at New York-Presbyterian Queens hospital. Additional process metrics included alliative care (PC) penetration rate, time to first PC consult, and Hospice Conversion Rate. A balancing metric was IP death after hospice referral. Plan-Do-Study-Act (PDSA) methodology was used. Multiple cycles of PDSA were performed. Results The hospital mortality index improved significantly to 0.78 (relative reduction of 35%). Secondary process metrics such as PC penetration rate, average length of stay admit-to-PC, and hospice conversion rate improved as well. IP death after hospice referral continues to trend below our historic rate of >20%. Conclusions A coordinated hospital-wide initiative for the early discussion of GOC may result in increased hospice discharges. Outcomes were sustained despite unanticipated palliative care and case management department staffing shortages.

An Intensive Longitudinal Assessment Approach to Surveilling Trajectories of Burnout over the First Year of the COVID Pandemic.

Frontline clinicians responding to the COVID-19 pandemic are at increased risk of burnout, but less is known about the trajectory of clinician burnout as caseloads increase and decrease. Personal and professional resources, including self-efficacy and hospital support, can attenuate the risk of burnout. Yet, empirical data documenting how burnout and resources changed as the pandemic waxed and waned are limited. This intensive longitudinal prospective study employed ecological momentary assessment methods to examine trajectories of burnout and resources over the pandemic's first year in a New York City hospital. A 10-item survey was emailed every 5 days to frontline clinicians (physicians, nurses, and physician assistants). The primary outcome was a single-item validated measure of burnout; predictors included daily hospital COVID-19-related caseloads and personal and professional resources. Clinicians (n = 398) completed the initial survey and an average of 12 surveys over the year. Initially, 45.3% of staff reported burnout; over the year, 58.7% reported burnout. Following the initial COVID peak, caseloads declined, and burnout levels declined. During the second wave of COVID, as caseloads increased and remained elevated and personal and professional resource levels decreased, burnout increased. This novel application of intensive longitudinal assessment enabled ongoing surveillance of burnout and permitted us to evaluate how fluctuations in caseload intensity and personal and professional resources related to burnout over time. The surveillance data support the need for intensified resource allocation during prolonged pandemics.

Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial.

Importance: The monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. Objective: To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo. Design, Setting, and Participants: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study included outpatients with SARS-CoV-2 infection at 47 sites across the United States. Participants could be symptomatic or asymptomatic; symptomatic patients with risk factors for severe COVID-19 were excluded. Data were collected from December 15, 2020, to March 4, 2021. Interventions: Patients were randomized to a single IV dose (523 patients) of casirivimab and imdevimab at 300, 600, 1200, or 2400 mg or placebo; or a single SC dose (292 patients) of casirivimab and imdevimab at 600 or 1200 mg or placebo. Main Outcomes and Measures: The primary end point was the time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative for SARS-CoV-2 at baseline. Results: Among 815 randomized participants, 507 (282 randomized to IV treatment, 148 randomized to SC treatment, and 77 randomized to placebo) were seronegative at baseline and included in the primary efficacy analysis. Participants randomized to IV had a mean (SD) age of 34.6 (9.6) years (160 [44.6%] men; 14 [3.9%] Black; 121 [33.7%] Hispanic or Latino; 309 [86.1%] White); those randomized to SC had a mean age of 34.1 (10.0) years (102 [45.3%] men; 75 [34.7%] Hispanic or Latino; 6 [2.7%] Black; 190 [84.4%] White). All casirivimab and imdevimab treatments showed significant virologic reduction through day 7. Least-squares mean differences in TWACB viral load for casirivimab and imdevimab vs placebo ranged from -0.56 (95% CI; -0.89 to -0.24) log10 copies/mL for the 1200-mg IV dose to -0.71 (95% CI, -1.05 to -0.38) log10 copies/mL for the 2400-mg IV dose. There were no adverse safety signals or dose-related safety findings, grade 2 or greater infusion-related or hypersensitivity reactions, grade 3 or greater injection-site reactions, or fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported. Conclusions and Relevance: In this randomized clinical trial including outpatients with asymptomatic and low-risk symptomatic SARS-CoV-2, all IV and SC doses of casirivimab and imdevimab comparably reduced viral load. Trial Registration: ClinicalTrials.gov Identifier: NCT04666441.

Factors Associated with Burnout among Resident Physicians Responding to the COVID-19 Pandemic: A 2-Month Longitudinal Observation Study.

BACKGROUND: Burnout during residency may be a function of intense professional demands and poor work/life balance. With the onset of the COVID-19 pandemic, NYC hospital systems were quickly overwhelmed, and trainees were required to perform beyond the usual clinical duties with less supervision and limited education. OBJECTIVE: The present longitudinal study examined the effects of COVID-19 caseload over time on burnout experienced by resident physicians and explored the effects of demographic characteristics and organizational and personal factors as predictors of burnout severity. METHODS: This study employed a prospective design with repeated measurements from April 2020 to June 2020. Participants were surveyed about their well-being every 5 days. Predictors included caseload, sociodemographic variables, self-efficacy, hospital support, perceived professional development, meaning in work, and postgraduate training level. RESULTS: In total, 54 resident physicians were recruited, of whom 50% reported burnout on initial assessment. Periods of higher caseload were associated with higher burnout. PGY-3 residents reported more burnout initially but appeared to recover faster compared to PGY-1 residents. Examined individually, higher self-efficacy, professional development, meaningful work, and hospital support were associated with lower burnout. When all four predictors were entered simultaneously, only self-efficacy was associated with burnout. However, professional development, meaningful work, and hospital support were associated with self-efficacy. CONCLUSION: Burnout among residency is prevalent and may have implications for burnout during later stages of a physician's career. Self-efficacy is associated with lower burnout and interventions to increase self-efficacy and the interpersonal factors that promote self-efficacy may improve physician physical and emotional well-being.

REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.

BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. METHODS: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. RESULTS: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. CONCLUSIONS: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19.

BACKGROUND: Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads. METHODS: In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients. RESULTS: Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log10 copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log10 copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody-negative at baseline, the corresponding percentages were 15% and 6% (difference, -9 percentage points; 95% CI, -29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group. CONCLUSIONS: In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.).

A Comprehensive Approach to Palliative Care during the Coronavirus Pandemic.

Context: The COVID-19 pandemic resulted in a surge of critically ill patients that strained health care systems throughout New York City in March and April of 2020. At the peak of the crisis, consults for palliative care increased four- to sevenfold at NewYork-Presbyterian (NYP), an academic health care system with 10 campuses throughout New York City. We share our challenges, solutions, and lessons learned to help peer institutions meet increased palliative care demands during future crises and address pre-existing palliative care subspecialist shortages during nonpandemic times. Methods: In response to the increased demand, palliative care physician and administrative leadership at NYP piloted multiple creative care models to expand access to palliative care outpatient and inpatient services. The care models included virtual outpatient management of existing patients, embedded palliative care staff, education for providers, multidisciplinary family support, hospice units (which allowed for family visitation), and team expansion through training other disciplines (primarily psychiatry) and deploying an ePalliative Care service (staffed by out-of-state volunteers). Conclusion: Our comprehensive response successfully expanded the palliative care team's reach, and, at the height of the pandemic, allowed our teams to meet the increased demand for palliative care consults. We learned that flexibility and adaptability were critical to responding to a rapidly evolving crisis. Physician and family feedback and preliminary data suggest that virtual outpatient visits, embedded staff, hospice units, and team expansion through training other disciplines and deploying ePalliative Care services were impactful interventions.