COVID-19 in Hospitalized Patients with Sickle Cell Disease

Introduction Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is estimated to affect more than 100,000 Americans. Current Centers for Disease Control statistics indicate that Black Americans die from COVID-19 at a disproportionately high rate, 13.6% of 449, 373 deaths but only account for 12.54% of the United States Population (CDC COVID Data Tracker accessed 5/5/2021). A voluntary clinical reported registry of COVID-19 infections in patients with SCD reported both high hospitalization rates (69%) and case fatality rates (7%) (Panepinto, 2020), but only reported data from March 20-May 21, 2020. A retrospective cohort review from England demonstrated a 4-fold increased risk of hospitalization and 2.6-fold increased risk of death due to COVID-19 for those patients with sickle cell disease compared to the general population (Hippisley-Cox, 2021). The unique constellation of SCD manifestations complicate both the diagnosis and management of COVID-19, particularly related to anticoagulation and transfusion practices. Understanding the impact of early exchange and anticoagulation would guide development of appropriate treatment guidelines and future understanding of pathophysiology. We report on the outcomes for all hospitalized inpatients with SARS-CoV-2 and SCD at institutions using Cerner electronic health record (EHR). Methods Exempted retrospective review approved by ChristianaCare IRB. We obtained deidentified data from the Cerner COVID Data Lab which includes information on all hospitalized inpatients with SARS-CoV-2 and sickle cell disease as documented by ICD 10 D57.XX from 12/10/2019-10/15/2020 at institutions that use the Cerner EHR. Those with sickle cell trait excluded. The data included 209 patients;1 patient had separate 2 visits, only the first visit in the data. Evaluated anticoagulation use, not dose. Descriptive statistics are given: percentages for categorical variables and mean (standard deviation) for continuous variables. Comparisons between patients who died or went to hospice versus patients who recovered were done using unadjusted chi-squared tests or t-tests. Results: Admission: 124 (74.3%) were afebrile (temp <100) 52 (28.4%) were tachypneic (RR >22) 10 (6.2%) were hypoxic (<92%) 7 (3.3%) were intubated during hospitalization Many patients had comorbidities including diabetes, hypertension, and congestive heart failure, but it was not clear if patients had multiple co-morbidities. Treatment: 16 (7.7%) got transfused RBC between 1.77 and 589.18 hours into admission 5 (2.4%) got Remdesivir, none of these patients died/went to hospice. No exchange transfusions, but maybe wasn't captured in coding data 149 (71.3%) received anticoagulant, dosing unable to be obtained so not known if this was prophylactic or treatment dosing. Outcomes: 158 (80.2%) discharged home 18 (9.1%) discharged facility 8 (4.1%) died 2 (1.0%) discharged hospice 11 (5.6%) left against medical advice 12 (5.7%) missing disposition data Those who died/went to hospice had longer hospital stays, were more likely to be hypoxic and initially tachypneic. None of these patients received remdesivir. Study included small numbers but those who died more likely to have hypertension, diabetes w/ and w/out complications, CHF. Discussion This data only included hospitalized patients, doesn't account for patients who remained outpatient so case fatality rate likely lower. 10/209 patients died- 4.8% fatality rate, 12 patients missing final discharge disposition. 18 went to facility, may have died as outpatient. Only a small number of patients received remdesivir and there were overall low rates of anticoagulation, concerning given SCD is a hypercoagulable state. Study limitations include only hospitalized patients in the dataset and only draws from Cerner EMR institutions, a 26% market share. Based on our own SCD population, only a small percentage of patients with SCD and COVID-19 hospitalized. Additionally, there is likely significant variability between institutions' treatment protocols, particularly in the early m nths of the data set. Finally, we could not adequately gauge severity of COVID-19 disease given notable variations in institutional resources. TABLES (in process): TABLE 1- Demographics- split by death/hospice vs. other dispositions TABLE 2- Admission Characteristics- Death/hospice vs. others TABLE 3- Treatments- Death/Hospice vs. others Disclosures: Lanzkron: Shire: Research Funding;Novartis: Research Funding;Bluebird Bio: Consultancy;CSL Behring: Research Funding;Imara: Research Funding;GBT: Research Funding;Pfizer: Current holder of individual stocks in a privately-held company;Teva: Current holder of individual stocks in a privately-held company;Novo Nordisk: Consultancy.

Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease: A National Alliance of Sickle Cell Centers Study

Background: Vaso-occlusive crises (VOC) are the most common acute complication of sickle cell disease (SCD). Crizanlizumab, an anti-P-selectin monoclonal antibody, is an FDA-approved disease-modifying therapy (DMT) for SCD patients (pts) aged ≥16 yrs to reduce the frequency of VOC. To better understand its use and impact, the National Alliance for Sickle Cell Centers (NASCC) conducted a retrospective study of pts prescribed crizanlizumab from 11/2019-6/30/2021. NASCC is a non-profit organization formed to support SCD centers in delivering quality comprehensive care by setting and adopting specific standards and advocating for improved health outcomes in SCD. This study describes the largest real-world cohort of pts treated with crizanlizumab. Methods: This is a two-part study. Part 1 was to evaluate NASCC center crizanlizumab practice and to summarize data on insurance approval and the frequency of drug discontinuation. Part 2 includes pt level data to evaluate reasons for discontinuation and acute care utilization pre and post therapy. Acute care use includes day hospital/infusion, emergency department visits, and hospitalizations for VOC (excluding COVID-19). The index date for each pt is defined as the 1st crizanlizumab infusion date. Chart review (electronic health records) was used to identify all acute care visits 12 months pre-index and ≤12 months post index. Acute care data will be analyzed in aggregate. Evaluation of center-specific use of crizanlizumab, time to initial site level formulary approval and drug discontinuation were analyzed. Pt level data collection is ongoing to include sufficient time post index date. VOC characteristics will be summarized using medians, median differences (pre/post treatment), and 95% confidence intervals. Additional evaluation of effectiveness of crizanlizumab will include analysis based on number of doses received, pre-treatment VOC burden, concomitant hydroxyurea (HU) use and genotype. Results: Data includes pts prescribed crizanlizumab at 11 NASCC centers. Site- formulary approvals to use crizanlizumab varied from 12/2019-12/2020. As a result, the 1st pt to receive treatment at each site varied from 1/15/2020-1/20/2021. Mean time from site-level approval to first infusion was 77 days (range: 0-394). Over 50% of sites received insurance denials mainly due to “insufficient medical necessity” or “medication not covered by the prescription plan.” Sites were able to successfully appeal denials for 71% of pts (Table 1). Treatment Delivery: Each site gives infusions over 30 minutes and the majority (64%) do not use pre-medication unless pts had reactions. Some sites use diphenhydramine/acetaminophen (3) or normal saline and ketorolac (1). All sites prescribe crizanlizumab to pts of all SCD genotypes. Pts Treated: 297 pts were prescribed crizanlizumab of whom 238 received ≥ 1 infusion. There was variation in number of pts/site (range 6-73, mean 21) due to time to site-level approval, insurance and pt population. Of these 238, 75 pts (32%) discontinued treatment (0-17 pts/site). Sites reported pts perceived lack of improvement or feeling their overall pain was increased, transportation issues and infusion related reactions (IRRs) characterized by pain as some of the reasons for discontinuation. Evaluation of real-world efficacy measured by changes in acute care utilization, including sub-analysis by genotype, pre-treatment VOC burden and concomitant HU use, are pending sample size dependent feasibility. Discussion: This is the first multi-center real-world analysis of crizanlizumab. Findings demonstrate some insurance barriers to therapy. The majority of pts who initiated crizanlizumab have remained on therapy;however, 1/3 of pts had lack of effect or barriers to care. Pt level data will include characteristics related to treatment failure or IRR. Improving the understanding of phenotype-specific response to novel therapies is essential in SCD. Conclusion: Post-approval therapies for rare diseases must undergo real-world evaluation to ensure study results transla e to the community. NASCC uses defined criteria for multidisciplinary care for Alliance inclusion and findings reflect the use of DMT in such centers. This is the first NASCC study of DMT in SCD. Part 2 of the study will give early insights into the effectiveness of crizanlizumab;long term follow-up is needed for a full understanding of its utility in SCD. [Formula presented] Disclosures: Kanter: Fulcrum Therapeutics, Inc.: Consultancy;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees;Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Graphite Bio: Consultancy;GuidePoint Global: Honoraria;Fulcrum Tx: Consultancy. Manwani: Novartis: Consultancy. Idowu: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding;Pfizer: Research Funding;Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Forma Therapeutics, Inc.: Research Funding;Ironwood: Research Funding. Treadwell: National Alliance of Sickle Cell Centers: Other: Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease. Clay: GBT: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria. Little: Hemex Health, Inc.: Patents & Royalties;Biochip Labs: Patents & Royalties. Desai: Global Blood Therapeutics: Honoraria, Research Funding;Novartis: Research Funding, Speakers Bureau;Pfizer: Other: Publication Fee, Research Funding;Forma: Consultancy;Foundation for Sickle Cell Research: Honoraria. Lanzkron: Shire: Research Funding;Pfizer: Current holder of individual stocks in a privately-held company;Bluebird Bio: Consultancy;Teva: Current holder of individual stocks in a privately-held company;Novo Nordisk: Consultancy;GBT: Research Funding;Imara: Research Funding;CSL Behring: Research Funding;Novartis: Research Funding.

Data-driven simulation of contagions in public venues

The COVID-19 pandemic triggered a global research effort to define and assess timely and effective containment policies. Understanding the role that specific venues play in the dynamics of epidemic spread is critical to guide the implementation of fine-grained non-pharmaceutical interventions (NPIs). In this paper, we present a new model of context-dependent interactions that integrates information about the surrounding territory and the social fabric. Building on this model, we developed an open-source data-driven simulator of the patterns of fruition of specific gathering places that can be easily configured to project and compare multiple scenarios. We focused on the greatest park of the City of Florence, Italy, to provide experimental evidence that our simulator produces contact graphs with unique, realistic features, and that gaining control of the mechanisms that govern interactions at the local scale allows to unveil and possibly control non-trivial aspects of the epidemic. © 2021 Society for Modeling & Simulation International (SCS).

Data-Driven Simulation of Contagions in Public Venues

The COVID-19 pandemic triggered a global research effort to define and assess timely and effective containment policies. Understanding the role that specific venues play in the dynamics of epidemic spread is critical to guide the implementation of fine-grained non-pharmaceutical interventions (NPIs). In this paper, we present a new model of context-dependent interactions that integrates information about the surrounding territory and the social fabric. Building on this model, we developed an open-source data-driven simulator of the patterns of fruition of specific gathering places that can be easily configured to project and compare multiple scenarios. We focused on the greatest park of the City of Florence, Italy, to provide experimental evidence that our simulator produces contact graphs with unique, realistic features, and that gaining control of the mechanisms that govern interactions at the local scale allows to unveil and possibly control non-trivial aspects of the epidemic. © 2021 SCS.