Health System Success in Delivering Bamlanivimab Within Post-acute and Long-Term Care Facilities

ObjectivesPost-acute and long-term care (PALTC) residents are disproportionately affected by coronavirus 2019 (COVID-19). We describe a health system approach that incorporated PALTC stakeholders to treat residents effectively and efficiently with monoclonal antibodies during the pandemic.DesignRetrospective observational.Setting and ParticipantsIntegrated health system headquartered in Sioux Falls, South Dakota, with urban hub and surrounding rural communities. Patients of the health system include PALTC and assisted living (AL) residents of facilities.MethodsMonoclonal Data Registry captured time to infusion after a positive COVID-19 test, residency (independent or PALTC), and site of infusion (PALTC, hospital outpatient, infusion center). AL residents are included in PALTC data. Registry limited to patients living in SD. Communication and operational resources were tailored to support PALTC infusions. The monoclonal antibody therapy administered to PALTC residents during the first 6 weeks after emergency use authorization (EUA) of monoclonal antibodies was bamlanivimab. The EUA for bamlanivimab was revoked due to lack of effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on April 16, 2021.ResultsThe results are analyzed for the 6 weeks after bamlanivimab EUA. In PALTC, there was a median of 3 days between positive test and infusion. The total number of monoclonal antibody infusions captured in the registry during this time was 87 PALTC on-site infusions.Conclusion and ImplicationsA collaborative approach between health system executives and PALTC experts quickly enabled access to potentially life-saving therapy to a vulnerable population. PALTC settings should be routinely included in health system investment and planning to improve the capacity of the system to achieve optimal outcomes, prevent unnecessary mortality, and preserve health care resources.     

SARS-CoV-2 Variants in Immunocompromised Patient Given Antibody Monotherapy

A 72-year-old immunocompromised man infected with severe acute respiratory syndrome coronavirus 2 received bamlanivimab monotherapy. Viral evolution was monitored in nasopharyngeal and blood samples by melting curve analysis of single-nucleotide polymorphisms and whole-genome sequencing. Rapid emergence of spike receptor binding domain mutations was found, associated with a compartmentalization of viral populations.     

Immunosuppression in kidney transplant recipients with COVID-19 infection – where do we stand and where are we heading?

The appropriate immunosuppressive regimen in kidney transplant recipients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19) infection remains unclear. The impact of direct virus injury complicated by dysregulated hyperimmune response with overwhelming release of various cytokines in COVID-19 infected subjects contributes to the complexity of management. The largest concern of the practicing clinicians at current time is how to tailor maintenance immune-modulating therapy during active viral infection and the efficacy of the soon-to-be upcoming immunization for COVID-19. This targeted review aims to cover most of the current evidence on the effect of key maintenance immunosuppressive agents in COVID-19 infection and proposes a line of management to specific scenarios on this very rapidly evolving subject.     

Comprehensive Treatment of Hematological Patients with SARS-CoV-2 Infection Including Anti-SARS-CoV-2 Monoclonal Antibodies: A Single-Center Experience Case Series

Simple SummarySARS-CoV-2 causes coronavirus disease (COVID-19) and poses a global health burden. Treatment strategies remain limited and mainly consist of dexamethasone; antiviral agents, such as remdesivir and molnupiravir; and SARS-CoV-2-specific monoclonal antibodies (mABs), including bamlanivimab, casirivimab/imdevimab combination, and, most recently, sotrovimab. SARS-CoV-2 mABs target specific proteins on the viral surface. Patients with hematologic malignancies represent an especially vulnerable cohort. Evidence for the use of SARS-CoV-2 mABs in these patients is scarce, creating an imbalance between urgently needed therapeutic strategies and a lack of randomized controlled trials. In this study, we summarize the characteristics of tolerability and clinical benefits of SARS-CoV-2 mAB application in patients with COVID-19 and hematologic malignancies admitted to our university hospital in Germany. We hope to provide some evidence that may contribute to the management of patients with hematologic malignancies in a world where COVID-19 remains a risk.AbstractPatients with hematologic malignancies are at high risk of exacerbated condition and higher mortality from coronavirus disease 2019 (COVID-19). Bamlanivimab, casirivimab/imdevimab combination, and sotrovimab are monoclonal antibodies (mABs) that can reduce the risk of COVID-19-related hospitalization. Clinical effectiveness of bamlanivimab and casirivimab/imdevimab combination has been shown for the Delta variant (B.1.617.2), but the effectiveness of the latter treatment against the Omicron variant (B.1.1.529) has been suggested to be reduced. However, the tolerability and clinical usage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific mABs in patients with hematologic malignancies are less specified. We present a retrospective case series analysis of all SARS-CoV-2-infected patients with hematologic malignancies who received SARS-CoV-2-specific mABs at our facility between February and mid-December 2021. A total of 13 COVID-19 patients (pts) with at least one malignant hematologic diagnosis received SARS-CoV-2-specific mABs at our facility, with 3 pts receiving bamlanivimab and 10 pts receiving casirivimab/imdevimab combination. We observed SARS-CoV-2 clearance in five cases. Furthermore, we observed a reduction in the necessity for oxygen supplementation in five cases where the application was administered off-label. To the best of our knowledge, we present the largest collection of anecdotal cases of SARS-CoV-2-specific monoclonal antibody use in patients with hematological malignancies. Potential benefit of mABs may be reduced duration and/or clearance of persistent SARS-CoV-2 infection.     

Neutralizing Antibody Therapeutics for COVID-19

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized controlled trial data evaluating nAbs in the ambulatory, hospitalized and prophylaxis settings. Two nAb cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab) and one nAb monotherapy (bamlanivimab) have been granted Emergency Use Authorization by the US Food and Drug Administration for the treatment of ambulatory patients who have a high risk of progressing to severe disease, and the European Medicines Agency has similarly recommended both cocktails and bamlanivimab monotherapy for use in COVID-19 patients who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Efficacy of nAbs in hospitalized patients with COVID-19 has been varied, potentially highlighting the challenges of antiviral treatment in patients who have already progressed to severe disease. However, early data suggest a promising prophylactic role for nAbs in providing effective COVID-19 protection. We also review the risk of treatment-emergent antiviral resistant “escape” mutants and strategies to minimize their occurrence, discuss the susceptibility of newly emerging SARS-COV-2 variants to nAbs, as well as explore administration challenges and ways to improve patient access.