We aimed to identify predictors of outcomes and survival in patients living in 4 major metropolitan areas who had sickle cell disease (SCD) and COVID-19 to inform best approaches to prevention and care. Data were collected at baseline and during the clinical course in SCD patients diagnosed with COVID-19 in four COVID-19 epicenters. Patients were followed up posthospital discharge for up to 3 months. Of sixty-six SCD patients with COVID-19, fifty patients (75%) required hospitalization, and seven died (10.6%). Patients with preexisting kidney disease (chronic kidney disease) were more likely to be hospitalized. The most common presenting symptom was vaso-occlusive pain. Acute chest syndrome occurred in 30 (60%) of the 50 hospitalized patients and in all who died. Older age and histories of pulmonary hypertension, congestive heart failure, chronic kidney disease, and stroke were more prevalent in patients who died, as were higher creatinine, lactate dehydrogenase, and D-dimer levels. Anticoagulation use while inpatient was twice less common in patients who died. All deaths occurred in individuals not taking hydroxyurea or any other SCD-modifying therapy. Patients with SCD and COVID-19 exhibited a broad range of disease severity. We cannot definitively state that the overall mortality is higher in patients with SCD, although our case fatality rate was ∼10% compared with ∼3% in the general population, despite a median age of 34 years. Individuals with SCD aged >50 years, with preexisting cardiopulmonary, renal disease, and/or stroke not receiving hydroxyurea, who present with high serum creatinine, lactate dehydrogenase, and D-dimer levels, are at higher risk of death, irrespective of genotype or sex.

Pulmonary embolism (PE) in the pediatric population is relatively rare when compared to adults; however, the incidence is increasing and accurate and timely diagnosis is critical. A high clinical index of suspicion is warranted as PE often goes unrecognized among children leading to misdiagnosis and potentially increased morbidity and mortality. Evidence-based guidelines for the diagnosis, management, and follow-up of children with PE are lacking and current practices are extrapolated from adult data. Treatment options include thrombolysis and anticoagulation with heparins and oral vitamin K antagonists, with newer direct oral anticoagulants currently in clinical trials. Long-term sequelae of PE, although studied in adults, are vastly unknown among children and adolescents. Additional research is needed in order to provide pediatric focused care for patients with acute PE.

Background and purpose Sickle cell disease (SCD) is a collection of rare inherited blood disorders affecting approximately 100,000 people in the U.S. and 20–25 million people globally. Individuals with SCD experience recurrent episodes of severe and unpredictable pain that are caused by vaso-occlusive crises (VOCs), a hallmark of the disease. VOCs are the primary cause of hospitalization in SCD, result in missed workdays and school days, and decrease quality of life (QoL). Although VOCs cause significant burden in the lives of individuals with SCD, there is no synthesis on the frequency of VOCs in the real world. This systematic literature review sought to identify literature describing the frequency of VOCs experienced by individuals with SCD in real-world settings. Methods MEDLINE and 6 congresses were searched (date range: January 1, 2000 to June 30, 2020). Studies were reviewed independently by two researchers. Studies assessing frequency or prevalence of VOCs or VOC-related outcomes were included. Results Of 1438 studies identified in the search, 52 met pre-specified inclusion and exclusion criteria. Reported frequency of VOCs varied widely ranging from a mean or median of 0 VOCs/year to 18.2 VOCs/year. The proportion of patients experiencing ≥ 3 VOCs/year ranged from 4 to 67% and the proportion of patients experiencing ≥ 5 VOCs/year ranged from 18 to 59%. Measures of VOC severity were limited, with 13 studies considering frequency of complicated VOCs and only 1 study reporting duration of VOC episodes. Conclusions This is the first study to systematically assess published evidence pertaining to VOCs in real-world settings. Reported VOC frequency in real-world settings varied widely, with a majority of studies only considering VOCs managed in an inpatient or outpatient setting. Studies that considered VOCs managed at home reported a higher frequency of VOCs, suggesting that many studies may underestimate the frequency of VOCs. This systematic literature review (SLR) highlights the need for consistent reporting of (1) self-reported VOCs, including those managed at home, (2) definitions of VOCs, (3) complicated VOCs, and (4) duration of VOC episodes in literature.

Clinical trials in sickle cell disease (SCD) often focus on health care utilization for painful vaso-occlusive crises (VOC). However, no objective, quantifiable pain biomarkers exist, pain is not specific to VOCs, health care utilization varies between patients, unreported at-home VOCs likely contribute to long-term outcomes, and patient-reported outcomes are seldom considered. This non-interventional, longitudinal, 6-month study aimed to develop tools to identify VOCs in SCD patients with or without health care utilization. Participants wore an actigraph device, tracking sleep and activity. SCD patients used an electronic patient-reported outcome (ePRO) tool collecting pain, medication, fatigue, and daily function. Patients self-reported when they experienced VOC pain (VOC day). Biomarkers were collected every 3 weeks (non-VOC). Self-reported VOCs triggered at-home or in-hospital blood collection. The study enrolled 37 participants with SCD; 35 completed the study. Participants reported 114 VOC events and 346 VOC days, of which 62.3% and 78.3%, respectively, were self-treated at home. The ePRO and actigraphy captured endpoints of pain, functionality, fatigue, activity, and sleep; each was significantly altered on VOC days compared with non-VOC days. Biomarkers collected at home or in hospital on VOC days were significantly altered compared with non-VOC baseline values, including leukocyte-platelet aggregates, microfluidic-based blood cell adhesion, interleukin-6, C-reactive protein, interleukin-10, tumor necrosis factor-alpha, and thrombin-antithrombin. ELIPSIS: demonstrates the feasibility of accurately monitoring out-of-hospital pain, using patient-reported VOC days as potential endpoints for clinical trials in SCD; showed changes in biomarkers and activity measured by actigraphy that may enable improved identification and assessment of VOCs.