Transitions experienced by mothers of children/adolescents with sickle cell disease in the context of the COVID-19 pandemic.

OBJECTIVE: To analyze the transitions experienced by mothers and children/adolescents with sickle cell disease after the emergence of the COVID-19 pandemic. METHOD: A qualitative study involving 19 mothers of children and adolescents with sickle cell disease. Data were obtained through semi-structured interviews via WhatsApp, followed by Thematic Analysis and Descending Hierarchical Classification with the help of Interface de R pour les Analyses Multidimensionnelles de Texteset de Questionnaires and interpreted in the light of Afaf Meleis' Transition Theory. RESULTS: Support from family members for displacement; mothers' adherence to the routine of daily stimuli and physical exercises favored healthy transitions; lack of remote health care; low socioeconomic resources; interruption of the physiotherapy service; and maternal overload favor unhealthy transitions. FINAL CONSIDERATIONS: Efforts/movements by mothers ensure the healthy transition of children/adolescents with sickle disease during the pandemic, while supporting their unhealthy transition.

Side effects following COVID-19 vaccination in pediatric patients with sickle cell disease.

Vulnerable patient populations have seen decreased rates of vaccination against SARS-CoV2-19 (COVID-19) due to hesitancies and distrust, magnified by a paucity of data for certain populations. The rate of COVID-19 vaccination in children with sickle cell disease (SCD) remains low despite the risk for severe complications, resulting in continued infections and hospitalizations from COVID-19. We sought to describe vaccine reactions, including vaso-occlusive crises, emergency department visits, and hospitalizations, in children with SCD. Our findings will start to provide the necessary vaccine side effect data to inform patients, caregivers, and clinicians considering the COVID-19 primary vaccination series.

Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race.

Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (n = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (<16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), P = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), P = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone.

A perspective on the sickle cell disease international COVID-19 registry.

To understand the risks and outcomes of COVID-19 in the sickle cell disease (SCD) population, our team established a rapid reporting registry to collect data on the course of COVID-19 illness in individuals with SCD. The registry includes cases reported voluntarily by providers. All data are collected through an online case report form available at covidsicklecell.org. The registry helped to recognize patients with SCD as a population at risk of severe COVID-19 illness and to identify comorbidities that put them at higher risk. In this report, we present data on 1045 reported COVID-19 cases based during a two-year long data collection period. Data include 590 (56.5%) children and 455 (43.5%) adults; 51.2% of total population were female. Most individuals (63.1%) had HbSS genotype. Majority of individuals experienced mild symptoms (62.2% of children, 55.6% of adults). We also present a perspective on setting up the registry and experiences through its growth.

Impact of COVID-19 infection among indian sickle cell disease patients.

Background: Sickle cell disease (SCD) is one of the most common hemoglobinopathy disorders and is widely prevalent in India, especially in the tribal population. SCD patients are prone to develop recurrent respiratory infections and related complications owing to the microvascular occlusion and impaired immunological response. Objectives: We aimed to determine the prevalence and impact of COVID-19 in SCD patients from India. Methodology: We conducted a cross-sectional study in Chandrapur district of Maharashtra, India, between August and October 2021. After taking informed consent, details of 300 SCD patients' demographic data, history of COVID-19 testing, infection, symptoms related to COVID-19 in the past 1 year, hospitalization, complications, mortality, COVID-19 vaccination, and side effects were recorded. Results: We found that 93 (31%) of SCD patients had influenza-like symptoms during the COVID-19 pandemic with symptoms of fever (81.72%), cough (35.48%), sore throat (18.27%), headache (15.05%), and breathlessness (7.52%). A total of 13 (4.33%) SCD among 300 SCD were tested as COVID positive. Majority of them were mild cases and the 1st dose of COVID-19 vaccine was received by 47 (29.37%) of SCD patients and 10 (6.02%) of the patient had received second dose of vaccine. Conclusion: Low incidence of COVID-19 and milder disease spectrum in our study cohort suggests that there is no increased risk of COVID-19 mortality and morbidity in SCD patients compared to general population. However, the reason for low COVID vaccination in our study could be due to the fear of complications of COVID vaccine.

COVID-19 Infection and Outcomes in Newborn Screening Cohorts of Sickle Cell Trait and Sickle Cell Disease in Michigan and Georgia.

The sickle cell mutation increases morbidity in those with sickle cell disease (SCD) and potentially sickle cell trait, impacting pulmonary, coagulation, renal, and other systems that are implicated in COVID-19 severity. There are no population-based registries for hemoglobinopathies, and they are not tracked in COVID-19 testing. We used COVID-19 test data from 2 states linked to newborn screening data to estimate COVID outcomes in people with SCD or trait compared with normal hemoglobin. We linked historical newborn screening data to COVID-19 tests, hospitalization, and mortality data and modeled the odds of hospitalization and mortality. Georgia's cohort aged 0 to 12 years; Michigan's, 0 to 33 years. Over 8% of those in Michigan were linked to positive COVID-19 results, and 4% in Georgia. Those with SCD showed significantly higher rates of COVID-19 hospitalization than the normal hemoglobin Black cohort, and Michigan had higher rates of mortality as well. Outcomes among those with the trait did not differ significantly from the normal hemoglobin Black group. People with SCD are at increased risk of COVID-19-related hospitalization and mortality and are encouraged to be vaccinated and avoid infection. Persons with the trait were not at higher risk of COVID-related severe outcomes.

Attitudes toward COVID-19 vaccine among pediatric patients with sickle cell disease and their caregivers.

OBJECTIVE: To evaluate attitudes toward vaccination and vaccine uptake regarding coronavirus disease 2019 (COVID-19) among pediatric patients with sickle cell disease (SCD) and their caregivers. PROCEDURE: Adolescent patients and caregivers of children with SCD were surveyed during routine clinic visits; we then conducted a logistic regression analysis to understand differences in vaccine status, while qualitative responses were coded thematically. RESULTS: Among respondents, the overall vaccination rate among adolescents and caregivers was 49% and 52%, respectively. Among the unvaccinated, 60% and 68% of adolescents and caregivers, respectively, preferred to remain unvaccinated, most commonly due to lack of perceived personal benefit from vaccination or mistrust in the vaccine. Multivariate logistic regression analysis showed that child's age (odds ratio [OR] = 1.1, 95% confidence interval [CI]: 1.0-1.2, p < .01) and caregiver education (measured by the Economic Hardship Index [EHI] score, OR = 0.76, 95% CI: 0.74-0.78, p < .05) were independent predictors of getting vaccinated. CONCLUSION: Despite the increased risk of severe illness due to COVID-19 in patients with SCD, vaccine hesitancy remains high in this population of families whose children have SCD. Fortunately, the reasons cited for deferring vaccination among those who are unvaccinated were largely due to barriers that may be overcome with quality communication around the utility of the vaccine and information about vaccine safety.

Clinical and laboratory differences between pediatric hospitalized patients with sickle cell disease infected or not by SARS-CoV-2.

OBJECTIVE: The aim of this study was to identify clinical and complete blood count differences between pediatric hospitalized patients with sickle cell disease infected or not by SARS-CoV-2 and compare the complete blood count of patients with sickle cell disease infected by SARS-CoV-2 before hospitalization and on admission. METHODS: This study was a single-center prospective cohort. Data were collected from medical records of pediatric inpatients with sickle cell disease under 18 years old infected or not with SARS-CoV-2 from the first visit to the hospital until discharge and from the last medical appointment. All patients were tested for SARS-CoV-2 by the real-time reverse transcription polymerase chain reaction. RESULTS: Among 57 pediatric patients with sickle cell disease hospitalized from March to November 2020 in a Brazilian academic hospital, 11 (19.3%) had a positive result for SARS-CoV-2. Patients infected by SARS-CoV-2 had a higher prevalence of comorbidities than the ones who were not infected (63.6 vs. 30.4%; p=0.046). During hospital stay, no clinical or complete blood count differences between groups were found. There was a decrease in eosinophil count on hospital admission in patients with sickle cell disease infected by SARS-CoV-2 (p=0.008). CONCLUSIONS: Pediatric hospitalized patients with sickle cell disease infected by SARS-CoV-2 had more comorbidities and had a decrease in eosinophil count between hospital admission and the last medical appointment.

Presentations and outcomes among sickle cell disease patients with COVID-19 at a large southern healthcare system.

OBJECTIVES: Compared with the general population, patients with sickle cell disease (SCD) typically have substantially reduced life expectancies. It is unclear whether SCD patients who acquire COVID-19 have higher rates of complications and mortality than the general population. We sought to elucidate COVID-19 presentation and outcomes in patients with SCD. METHODS: Using retrospective chart review, we evaluated demographic characteristics, presenting symptoms, chest imaging findings, blood transfusion requirements, need for mechanical ventilation or pressor support, medication administration (including remdesivir and dexamethasone), and survival among individuals with SCD hospitalized with COVID-19 from March 2020 to December 2021. RESULTS: Among 72 SCD patients, increased pain was the most common presenting symptom followed by cough, fever, and dyspnea. Thirty-seven (44%) received simple transfusion and 14 (17%) underwent exchange transfusion. Lung imaging findings suggestive of COVID-19 were observed in 27 (37%) patients; 21 (29%) patients were treated with remdesivir and 26 (35%) received dexamethasone. Three patients (4%) required mechanical ventilation and pressor support; all three died from COVID complications. CONCLUSIONS: Pain is the most common presenting symptom in SCD patients with COVID-19. We observed a mortality rate higher than that among the general population among patients who required mechanical ventilation and pressor support.

The impact of COVID-19 in children with Sickle Cell Disease: Results of a multicentric registry.

OBJECTIVE: To analyze the outcomes of children with sickle cell disease (SCD) and COVID-19. METHOD: A multicenter prospective study was conducted in five hematological centers from Central and Southeast Brazil, starting in April 2020. The variables recorded include clinical symptoms, diagnostic methods, therapeutic measures, and treatment sites. The clinical repercussions of the infection on the initial treatment and the overall prognosis were also evaluated. RESULTS: Twenty-five unvaccinated children, aged 4 to 17 years, with SCD and a positive SARS-CoV-2 RT-PCR result participated in this study. Patients were classified as SCD types SS (n = 20, 80%) and SC (n = 5, 20%). Clinical characteristics and evolution were similar in both groups (p>0.05), except for the fetal hemoglobin value which was higher among the SC patients (p = 0.025). The most frequent symptoms were hyperthermia (72%) and cough (40%). Three children were admitted to the intensive care unit, all of whom were overweight/obese (p = 0.078). No deaths were observed. CONCLUSIONS: Although SCD leads to specific complications, the results found in this sample suggest that COVID-19 does not seem to carry an increased mortality risk in pediatric patients with this disease.

Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): statistical and qualitative analysis plan for a randomised controlled feasibility trial.

BACKGROUND: There are significant knowledge gaps regarding the effectiveness of serial prophylactic exchange blood transfusion (SPEBT) for pregnant women with sickle cell disease (SCD). The protocol for the randomised feasibility trial assessing SPEBT versus usual care in women with SCD (TAPS2 trial) has previously been published. This publication outlines the statistical and qualitative analysis plan for the study. METHODS AND DESIGN: TAPS2 is a randomised two-arm phase 2 feasibility trial with a nested qualitative study and health economic evaluation. Up to 50 pregnant women with SCD and a singleton pregnancy will be recruited and individually randomised to either SPEBT approximately every 6-10 weeks until delivery (intervention arm) or to usual care (control arm). Information will be collected on a range of feasibility and clinical outcomes. RESULTS: Due to the impact of COVID-19 on study recruitment, the initial study period of 24 months was extended to 48 months. Other protocol updates designed to mitigate the impact of COVID-19-related disruption included allowing for remote consent and conducting all qualitative interviews by telephone. The primary outcome for the trial is the overall recruitment rate. The number of women screened, eligible, consented, randomised and withdrawn will be summarised as a CONSORT flow diagram. Differences in clinical outcomes will additionally be presented as an initial assessment of efficacy and to inform sample size calculations for a future definitive trial. Qualitative interviews with trial participants and clinicians will be analysed using reflexive thematic analysis; data from interviews with participants who declined to participate in the trial will be extracted and incorporated into summary tables to report key findings. The health economic analysis plan is not covered by this update. CONCLUSION: The publication of this analysis plan is designed to aid transparency and to reduce the potential for reporting bias. TRIAL REGISTRATION: NIH registry ( www. CLINICALTRIALS: gov ), registration number NCT03975894 (registered 05/06/19); ISRCTN ( www.isrctn.com ), registration number ISRCTN52684446 (retrospectively registered 02/08/19).

Risk of vaso-occlusive episodes in patients with sickle cell disease exposed to systemic corticosteroids: a comprehensive review.

INTRODUCTION: Sickle cell disease (SCD) is the most frequent inherited disorder in the world. It is caused by a single amino acid mutation on the beta-globin chain, which lead to red blood cell deformation, haemolysis, and chronic inflammation. Clinical consequences are vaso-occlusives crisis, acute chest syndrome, thrombosis, infection, and chronic endothelial injury. AREAS COVERED: Corticosteroids are an old therapeutic class, that are inexpensive and widely available, which can be administered in different forms. Their adverse effects are numerous and well-known. This class could appear to be useful in SCD treatment due to its anti-inflammatory effect. Moreover, corticosteroids remain an essential therapeutic class for many indications, besides SCD. Although specific adverse effects of corticosteroids have been suspected in SCD patients for decades, recent papers has reported strong evidence of specific and severe adverse effects in this population. Based on a literature review, we will discuss pathophysiological considerations, consequences, and practical use of corticosteroids in SCD. EXPERT OPINION: High corticosteroid doses, for any indication , induce vaso-occlusive crises, acute chest syndrome, and re-hospitalization in patients with SCD. There is no evidence of any benefits of corticosteroid use in the SCD acute events. Prevention by hydroxyurea and/or red blood cell transfusion or exchange should be discussed when corticosteroid use is indispensable.

Routine Ophthalmological Examination Rates in Adults with Sickle Cell Disease Are Low and Must Be Improved.

The American Academy of Ophthalmology and the National Heart, Lung and Blood Institute recommend patients with sickle cell disease (SCD) undergo dilated funduscopic exams (DFE) every 1-2 years to screen for sickle retinopathy. There is a paucity of data on the adherence rate to these guidelines; a retrospective study was performed to evaluate our institution's adherence. A chart review of 842 adults with SCD, seen 3/2017-3/2021 in the Montefiore healthcare system (All Patients), was done. Only about half of All Patients (n = 842) had >1 DFE during the study period (Total Examined Patients, n = 415). The Total Examined Patients were categorized as screening, those without retinopathy (Retinopathy-, n = 199), or follow-up, including individuals previously diagnosed with retinopathy (Retinopathy+, n = 216). Only 40.3% of screening patients (n = 87) had DFE at least biennially. As expected, there was a significant decrease in the average DFE rate of the Total Examined Patients after the COVID-19 pandemic started (13.6%) compared to pre-COVID (29.8%, p < 0.001). Similarly, there was a significant decrease in the screening rate of Retinopathy- patients from 18.6% on average pre-COVID to 6.7% during COVID (p < 0.001). This data shows the sickle retinopathy screening rate is low and innovative approaches may need to be employed to remedy this issue.

Evidence-based management of pregnant women with sickle cell disease in high-income countries.

Globally, patients living with sickle cell disease are now surviving to reproductive age, with life expectancy approaching 50 years in most countries. Thus, reproductive options are now essential for patients living with the condition. However, it can be associated with maternal, delivery, and fetal complications. Outcomes may vary depending on the level of expertise and resources. In this piece we provide an optional guideline for managing sickle cell disease in pregnancy. The therapeutic option of serial exchange prophylactic transfusion has been offered in the context of a clinical trial (TAPS2).

Emergency department visits and hospitalizations for pediatric vaso-occlusive pain events during the COVID-19 pandemic.

The coronavirus SARS-CoV-2 (COVID-19) pandemic altered all aspects of life, including healthcare. During the pandemic, social distancing led to decreased transmission of typical viral illnesses, leading to a decrease in these pediatric admissions. Studies have shown that pediatric emergency department (ED) visits and hospitalizations decreased during the pandemic, which may have led to some unmet healthcare needs and delays in treatment. Little is known about the effect of the COVID-19 pandemic on ED visits and hospitalizations specifically for pediatric sickle cell pain. A retrospective review across hospitals in the Northwell Health system was conducted to compare the ED visits and hospitalizations for pediatric patients with sickle cell pain during 2020 (the year of the pandemic), the following year (2021), and the 2 years prior to the pandemic (2018, 2019). The average length of stay for patients hospitalized with vaso-occlusive events was also compared between these years. Total 511 patient encounters for patients seen and discharged home from the ED and 985 hospitalization encounters were included over the 4-year timespan. ED visits per year decreased significantly in 2020 compared with the 2 years prior (p < .001): 91 visits in 2020, 162 visits in 2019, and 143 visits in 2018. The number of ED visits for pediatric vaso-occlusive events trended upward in 2021 to 115. Hospitalizations also decreased in 2020 compared to the 2 years prior (n = 202 vs 196; p < .001), compared with 298 in 2019 and 289 in 2018. The number of patients hospitalized remained stable in 2021 (n = 202 vs 196). There was a statistically significant increase in the median length of stay in 2020 compared to years prior (p = .002): median (interquartile range [IQR]): 4.0 days (2-6 days) in 2020 compared to 3.0 days (2-5 days) in 2018 and 2019. ED encounters and hospitalizations for pediatric patients with sickle cell disease pain decreased during the pandemic; however, admitted patients had a longer median length of stay.

Telemedicine in sickle cell disease: Patient, parent, and provider perspectives.

INTRODUCTION: Patients with sickle cell disease (SCD) need frequent health maintenance visits and may face barriers accessing care. Telemedicine, during COVID pandemic, has provided a unique model of care to improve access; however, potential barriers and satisfaction with its use in SCD have not been fully evaluated. OBJECTIVE: To determine caregiver, patient, and healthcare provider (HCP) perspectives and satisfaction with telemedicine in healthcare delivery. METHODS: We surveyed patients with SCD, caregivers, and HCP, who participated in at least one telemedicine visit from March 2020 to June 2021, using the Telemedicine Usability Questionnaire (TUQ). We also accessed and compared the Press Ganey surveys completed by families who completed a telemedicine or in-person visit. Data were summarized using descriptive statistics. The internal reliability of TUQ was assessed using Cronbach's coefficient alpha. Press Ganey data comparing satisfaction with telemedicine versus in-person visits were analyzed by Mann-Whiney U test. RESULTS: Fifty-two patients/caregivers and 10 HCP completed the survey. Patients/caregivers rated satisfaction "excellent" in the five areas (Usefulness, Ease of use, Effectiveness, Reliability and Satisfaction). HCP rated Usefulness, Ease of use, Effectiveness, Satisfaction as "good," and Reliability as "excellent." Press Ganey scores for satisfaction with care for telemedicine and in-person visits were not statistically different (p > .05). DISCUSSION: We found high satisfaction for caregivers and patients as well as HCP in the delivery of clinical services via telemedicine for SCD. We suggest that telemedicine is a viable option for this population and may help overcome the barriers SCD families often face accessing care.

Thrombo-inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin (preprint)

People with sickle cell disease (SCD) are at greater risk of severe illness and death from respiratory infections, including COVID-19 than people without SCD (Centers for Disease Control and Prevention, USA). Vaso-occlusive crises (VOC) in SCD and severe SARS-CoV-2 infection are both characterized by thrombo-inflammation mediated by endothelial injury, complement activation, inflammatory lipid storm, platelet activation, platelet-leukocyte adhesion, and activation of the coagulation cascade. Notably, lipid mediators, including thromboxane A2, significantly increase in severe COVID-19 and SCD. In addition, the release of thromboxane A2 from endothelial cells and macrophages stimulates platelets to release microvesicles which are harbingers of multicellular adhesion and thrombo-inflammation. Currently, there are limited therapeutic strategies targeting platelet-neutrophil activation and thrombo-inflammation in either SCD or COVID-19 during acute crisis. However, due to many similarities between the pathobiology of thrombo-inflammation in SCD and COVID-19, therapies targeting one disease may likely be effective in the other. Therefore, the preclinical and clinical research spurred by the COVID-19 pandemic, including clinical trials of anti-thrombotic agents, are potentially applicable to VOC. Here, we first outline the parallels between SCD and COVID-19; second, review the role of lipid mediators in the pathogenesis of these diseases and lastly, examine the therapeutic targets and potential treatments for the two diseases.

Vaso-occlusive Pain Crisis Mimicking Mandibular Abscess in an Adolescent with Sickle Cell Disease.

In people with sickle cell disease (SCD), oral abscesses are concerning clinical conditions and carry a high risk of postoperative sickle cell complications. We present an unusual case of a 14-year-old girl with SCD whose initial presentation of facial swelling, headaches, jaw pain, and paresthesia mimicked an odontogenic abscess. She was diagnosed with vaso-occlusive crisis in the mandibular bone and successfully managed noninvasively. This is among the youngest cases of paresthesia in the lower lip in SCD, which provided a clue that postponing invasive aspiration or biopsy was possible under empiric antibiotics and close observation.

Reflections from a Psychologist Working with Sickle Cell and Thalassaemia Patients during the COVID-19 Pandemic.

Sickle cell disease and thalassaemia are life-long haematological diseases that can impact the quality of life of patients. This impact on quality of life can require intermittent psychological input throughout the lifespan for management. Managing everyday life during the COVID-19 pandemic could be challenging for people with these health conditions, which could impact their health, their mood and anxiety, their perception of control, and their engagement with their regular healthcare services. This report describes the characteristics of these health conditions and discusses reflections, from a specialist psychology service working with this clinical population, about the impact of COVID-19 on patient engagement with the service. The main aim of this report is to highlight the relevance and usefulness of videoconferencing as a therapy format, suggest implications for further service development and suggest alternate ways of working therapeutically with clients.