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Abstract Background Remdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In prior work, those who continued remdesivir in an outpatient setting had better outcomes. Here, we assessed patients’ perspectives and the economic impact of this outpatient practice. Methods During a one-year period, 3,029 patients received remdesivir for COVID-19 in the hospital; of them, 542 were dismissed to continue remdesivir in the outpatient setting and were surveyed. The cost of care was compared between those who remained in the hospital vs. those who were dismissed. Results 470 of 542 patients were surveyed, and 93 (19.8%) responded. Responders were older than non-responders (median, 63 vs. 58 years). The majority (70.5%) had symptoms resolved by the time of the survey. Ten patients (11.4%) had persistent symptoms attributed to long COVID-19, including fatigue (30.1%), brain fog (23.7%), and insomnia (18.3%). 73.8% were excited to learn about the outpatient remdesivir program. The majority (81.0%) felt that receiving therapy at home was the right decision; 79.5% had support and felt the benefits of completing treatment at home. The majority were satisfied with communication before (75.6%) and during (80.5%) the outpatient appointment, information on benefits (80.3%) and risks (58.5%), time spent at the infusion center (88.6%), quality of care (82.3%) and overall experience (76.0%). The benefits of treatment were high-value (82.6%), while the infusions' cost, inconvenience, and discomfort were unimportant for most responders. After adjusting for gender, comorbidity score, and WHO scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p< .01). During this study, we estimated a total of 1,077 hospital room-days were made available to other patients. Conclusion An outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients hospitalized for COVID-19. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital rooms for other patients needing critical services. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Bijan J. Borah, Ph.D., Boehringer Ingelheim: Advisor/Consultant|Exact Sciences: Advisor/Consultant Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Abstract Introduction During the early phase of the coronavirus disease 2019 (COVID‐19), remdesivir was only approved for hospitalized patients. Our institution developed hospital‐based, outpatient infusion centers for selected hospitalized patients with COVID‐19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods Retrospective study of all hospitalized adult patients with COVID‐19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results Among 3029 hospitalized patients who received treatment with remdesivir for COVID‐19, the majority (89.5%) completed the recommended 5‐day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06–0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27–2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5‐day course of remdesivir (aOR 2.07, 95% CI 1.45–2.95, p < 0.001). Conclusions This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5‐day course of remdesivir.

ImportanceDirect oral anticoagulant (DOAC)–associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.ObjectiveTo evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.Data SourcesPubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.Study SelectionThe eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.Data Extraction and SynthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.Main Outcomes and MeasuresThe primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.ResultsA total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.Conclusions and RelevanceIn the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from 11/6/2020 to 11/5/2021 at one of the Mayo Clinic hospitals. Results: Among 3,029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended the five-day course. Among them, 2,169 (80%) completed treatment during hospitalization, while 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p<0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p=0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p<0.001). Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.

Abstract Background Antispike monoclonal antibodies are recommended for early treatment of high-risk persons with mild to moderate coronavirus disease 2019 (COVID-19). However, clinical outcomes of their use during the severe acute respiratory syndrome coronavirus 2 Omicron wave are limited. Methods This is a descriptive retrospective study of high-risk adult patients who received treatment with sotrovimab (January 1–March 20, 2022) or bebtelovimab (March 21–April 30, 2022). The primary outcome was the proportion of patients who progressed to severe outcome within 30 days after receiving antispike-neutralizing monoclonal antibody infusion. Results A total of 3872 high-risk patients (median age, 62.7 years; 41.1% male) with mild to moderate COVID-19 received sotrovimab (n = 2182) or bebtelovimab (n = 1690). Among sotrovimab-treated patients, the most common comorbidities were an immunosuppressed condition (46.7%), hypertension (38.2%), and diabetes (21.2%). The rates of severe outcome, intensive care unit (ICU) admission, and mortality were 2.2%, 1.0%, and 0.4%, respectively, after sotrovimab infusion. Among bebtelovimab-treated patients, the most common comorbidities were hypertension (42.7%), diabetes (17.1%), and an immunosuppressed condition (17.0%). The rates of severe disease, ICU admission, and mortality were 1.3%, 0.5%, and 0.2%, respectively, after bebtelovimab infusion. Older age, immunosuppressed status, and several comorbidities were associated with severe disease progression, while COVID-19 vaccination was associated with lower risk. No anaphylaxis was reported during monoclonal antibody infusion. Conclusions This real-world analysis of a large cohort of high-risk patients demonstrates low rates of severe disease after treatment with sotrovimab during the era dominated by Omicron B.1.1.529 and after treatment with bebtelovimab during the era dominated by BA.2 and Omicron subvariants.

Abstract The effectiveness of bebtelovimab in real-world settings has not been assessed. In this retrospective cohort study of 3607 high-risk patients, bebtelovimab was used more commonly than nirmatrelvir-ritonavir for treatment of coronavirus disease 2019 (COVID-19) among older patients, immunosuppressed patients, and those with multiple comorbid conditions. Despite its use in patients with multiple comorbid conditions, the rate of progression to severe disease after bebtelovimab (1.4% [95% confidence interval, 1.2%–1.7%]) was not significantly different from that for nirmatrelvir-ritonavir treatment (1.2% [.8%–1.5%]). Our findings support the emergency use authorization of bebtelovimab for treatment of COVID-19 during the Omicron epoch dominated by BA.2 and subvariants.

Abstract Background Bamlanivimab and casirivimab-imdevimab are authorized for treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk patients. We compared the outcomes of patients who received these therapies to identify factors associated with hospitalization and other clinical outcomes. Methods Adult patients who received monoclonal antibody from 19 November 2020 to 11 February 2021 were selected and divided into those who received bamlanivimab (n = 2747) and casirivimab-imdevimab (n = 849). The 28-day all-cause and COVID-19–related hospitalizations were compared between the groups. Results The population included 3596 patients; the median age was 62 years, and 50% were female. All had ≥1 medical comorbidity; 55% had multiple comorbidities. All-cause and COVID-19–related hospitalization rates at 28 days were 3.98% and 2.56%, respectively. After adjusting for medical comorbidities, there was no significant difference in all-cause and COVID-19–related hospitalization rates between bamlanivimab and casirivimab-imdevimab (adjusted hazard ratios [95% confidence interval], 1.4 [.9–2.2] and 1.6 [.8–2.7], respectively). Chronic kidney, respiratory and cardiovascular diseases, and immunocompromised status were associated with higher likelihood of hospitalization. Conclusions This observational study on the use of bamlanivimab and casirivimab-imdevimab in high-risk patients showed similarly low rates of hospitalization. The number and type of medical comorbidities are associated with hospitalizations after monoclonal antibody treatment.