Pregnancy Outcomes in Women with Sickle Cell Disease in Ireland: A Retrospective Review

Background: Sickle cell disease (SCD) is one of the most common single gene disorders worldwide and is characterised by significant morbidity and early mortality.[1] Pregnancy in SCD is associated with an increased risk of maternal and foetal complications.[2,3] The 2011 RCOG and the 2021 BSH guidelines[5,6] on the management of pregnancy in SCD have provided the basis for best practice care in the UK over the past decade and is the guidance which we follow in Ireland. To date, there is no published data on outcomes for pregnant women with SCD in Ireland. The number of Irish patients with SCD has risen over the past 20 years. Without a national database, the exact prevalence is not known but currently there are at least 600 adults and children with SCD in Ireland, whose population is just over 5 million.[4] Aims: Our study assesses outcomes of pregnant patients with SCD from 2015 to 2022. Our aims were to: * Assess adherence to current guidelines * Assess pregnancy outcomes and maternal complications * Assess transfusion rates amongst our patient cohort. Method(s): This is a retrospective cohort study. We do not have a directly matched cohort, but have compared our findings to published data on Irish pregnancy outcomes from the Irish Maternity Indicator System National Report and have correlated our findings with studies of women with SCD who were managed in UK centres.[8,9,10] Results: We reviewed outcomes of 29 pregnancies in 19 women over a 7-year period. The median age was 29 (range 20-41) and the predominant maternal sickle genotype was HbSS (65.5%). Before conception, 55.2% of cases had pre-existing complications of SCD, including acute chest syndrome (ACS), pulmonary hypertension (PHTN) and prior stroke. In accordance with current guidelines, 100% of women (n=29) were prescribed folic acid, penicillin, and aspirin prophylaxis. 51.7% (n=15) of women had documented maternal complications during pregnancy, including ACS (34%), vaso-occlusive crisis (34%), gestational diabetes (10%), VTE (3%) and UTI (3%). Two women (7%) developed Covid-19 pneumonitis despite vaccination. There was one case of maternal bacteraemia (3%). 65.5% of cases (n=19) required blood transfusion during pregnancy. One woman was already on a blood transfusion programme for disease modification prior to pregnancy. In 6 cases (20.6%), a transfusion programme was commenced during pregnancy due to prior pregnancy complications or intrauterine growth restriction. During pregnancy, 27.6% (n=8) of women required emergency red cell exchange for ACS. Prior studies have suggested that between 30% and 70% of pregnant women with SCD require at least one blood transfusion during pregnancy.[8,9,10] By comparison, only 2.6% of the Irish general obstetric population required transfusion during pregnancy.[7] 20.6% (n=6) of births were preterm at <37 weeks' gestation. There was one live preterm birth (3%) at <34 weeks and one intrauterine death (3%) at 23 weeks' gestation. Similar to UK data[9], 31% of women required critical care stay (n=9) during pregnancy, in comparison with 1.44% nationwide in 2020.[7] Conclusion(s): It is well established that pregnancy in SCD is high risk, and despite adherence to current guidelines, we have shown very high rates of critical care admission, significant transfusion requirement and hospital admissions. Our findings are comparable to published UK outcomes and they further support the need for a comprehensive specialist care setting for this patient cohort.

The Evolution of the Covid-19 Pandemic in Pediatric Patients with Sickle Cell Disease: From Alpha to Omicron

Background: Approximately two years ago, COVID-19 was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and through genomic surveillance, we have seen the emergence of variants of SARS-CoV-2. In the United States, over 78 million cases and >900,000 deaths attributable to COVID-19 have been reported. SCD was identified as a risk factor for severe COVID-19 disease in adults and pediatric patients. The emergence of novel SARs- CoV-2 variants has led to challenges in diagnosis, treatment, and prediction of long-term sequelae in individuals with SCD and COVID-19. Aim(s): We compare the overall seasonal variation of COVID-19 variants and patterns of healthcare utilization and clinical presentation over time in pediatric patients with SCD and COVID-19 at Children's National Hospital (CNH). Method(s): Our single-center, observational cohort study included 193 pediatric patients with SCD (0-21 years) with PCR-confirmed SARSCoV- 2 infection between March 31, 2020, and January 31, 2022. Per the SECURE SCD Registry definitions, clinical severity was classified as asymptomatic, mild, moderate, and severe. Result(s): A total of 193 unique patients with SCD and positive SARS-CoV-2 PCRs between March 2020-January 2022 were included in our registry. Most patients were female (51.8%), and the mean age was 11.2 years (SD 6.5 years). Most of the cohort resides in Maryland (N=135), and HbSS was the dominant genotype (69.4%). During the alpha dominant variant of the COVID-19 pandemic (March 2020- June 2021) there were 70 cases, followed by 40 cases during the Delta variant (July 2021- December 19, 2021), and 83 cases during the Omicron variant dominance (from December 20, 2021-January 31,2022). There were 149 patients (77%) that presented to the emergency department (ED) or were hospitalized. There were a total of 80 hospitalizations (41.5%), and a relative comparison showed that the percentage of hospitalizations was highest during the delta wave (47.5%) and lowest during the omicron wave (36.1%) (p= 0.407). ED-only utilization was highest in the era of omicron (43.4%, N=36), followed by delta (32.5%, N=13), and then alpha (30%, N=21)(p=0.197). The most common SCD-related complication was vaso-occlusive (VOC) pain (33%, N=64) which accounted for half of all hospital admissions (51%, N=41 of 80). Acute chest syndrome (ACS) was reported in 40% (N=32) of admitted patients and was highest in the alpha era (54.8%, N=17). The use of blood transfusion therapy was highest in the alpha (N=17) and delta (N=14) variants, while Remdesivir use was highest in omicron (N=15). A total of 6 patients received monoclonal antibodies (Delta, N=4;omicron, N=2). Throughout all the variants, there was a significant difference in COVID-19 clinical severity (p>0.005). Of the patients classified as asymptomatic (13%, N=25), seventy-two percent (n=18) were diagnosed during the alpha variant. Mild severity was the most prevalent (69%, N=134), with the omicron variant having the highest cases (51.5%, N=69). Severe cases were observed in all variants (6.7%, N=13) but were most prevalent during the alpha variant (46.2%, N=6). Summary - Conclusion(s): Interestingly, while the relative percentage of hospitalizations was lowest during the omicron wave, it saw the highest percentages of ER utilization. Overall, COVID-19 remains mild in pediatric patients with SCD, and notably, there was higher health care utilization in the omicron era.

Impact of the SARS-CoV-2 infection in individuals with sickle cell disease: an integrative review.

Sickle cell disease is the most common hemoglobinopathy among humans. As the condition promotes susceptibility to infections, chronic inflammation, and hypercoagulability disorders, several international agencies have included individuals with this disease in the COVID-19 risk group for severe outcomes. However, available information about the subject is not properly systematized yet. This review aimed to understand and summarize the scientific knowledge about the impact of SARS-CoV-2 infection in patients with sickle cell disease. Searches were performed in the Medline, PubMed, and Virtual Health Library databases based on descriptors chosen according to the Medical Subject Headings. We analyzed studies published between 2020 and October 2022, developed with qualitative, quantitative, or mixed methodology, and written in English, Spanish, or Portuguese. The search resulted in 90 articles organized into six categories. There is disagreement in the literature about how different aspects related to sickle cell disease, such as chronic inflammation status, hypercoagulability, hemolytic anemia, use of hydroxyurea, and access to medical care interference with the clinical course of COVID-19. These topics deserve further investigation. It is evident, however, that the infection may manifest in an atypical way and act as a trigger for the development of sickle cell-specific complications, such as acute chest syndrome and vaso-occlusive crises, conditions that are associated with great morbidity and mortality. Therefore, healthcare professionals must be aware of the different forms of presentation of COVID-19 among these individuals. Specific guidelines and therapeutic protocols, as well as public policies for sickle cell individuals, must be considered. Systematic review registration: This review (https://doi.org/10.17605/OSF.IO/NH4AS) and the review protocol (https://osf.io/3y649/) are registered in the Open Science Framework platform.

Thrombo-Inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin.

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.

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.

More Than Meets the Eye: Orbital Swelling in an Adolescent with Sickle Cell Disease

Periorbital swelling is a clinical presentation with a broad differential and potentially deleterious consequence. Causes range from benign, including allergic reaction, to vision-and life-threatening, including orbital cellulitis and orbital infarction. The recent climate of SARS-CoV-2 has further complicated this differential, as the virus poses broad clinical presentations with new manifestations reported frequently. Rapid identification of the underlying etiology is crucial, as treatment approaches diverge greatly. Here, we report the case of an African American adolescent male with a history of homozygous sickle cell anemia presenting to an inner city hospital with bilateral periorbital swelling amid the coronavirus pandemic. Differentials including orbital cellulitis, COVID-MIS-C, orbital inflammatory syndrome, Hoagland sign, and orbital infarction secondary to sickle cell crisis are contrasted. We contrast our case with 12 case reports of orbital infarction in the setting of sickle cell crisis within the past 10 years, highlighting how these presentations, along with commonly reported findings of orbital infarction, compare with our patient. Copyright © 2022 Tehran University of Medical Sciences.

COVID-19 and Sickle Cell Disease in the Province of Quebec, Canada: Outcomes after Two Years of the Pandemic.

BACKGROUND: Patients with sickle cell disease (SCD) are considered at higher risk of severe COVID-19 infection. However, morbidity and mortality rates are variable among countries. To date, there are no published reports that document outcomes of SCD patients with COVID-19 in Canada. METHODS: A web-based registry was implemented in June 2020 capturing outcomes of SCD patients with COVID-19 from March 2020 to April 2022 and comparing them to the general population of Quebec, Canada. RESULTS: After 24 months of the pandemic, 185 SCD patients with confirmed SARS-CoV-2 infection were included in the registry. Overall, the population was young (median age 12 years old) and had few comorbidities. No deaths were reported. Risk of hospitalization and admission to intensive care unit (ICU) because of COVID-19 was higher in patients with SCD than in the general population (relative risks (RR) 5.15 (95% confidence interval (95% CI) 3.84-6.91), p ˂ 0.001 and 4.56 (95% CI 2.09-9.93) p ˂ 0.001). A history of arterial hypertension or acute chest syndrome in the past 12 months was associated with a higher risk of severe disease (RR = 3.06 (95% CI 1.85-5.06) p = 0.008 and 2.27 (95% CI 1.35-3.83) p = 0.01). Hospitalized patients had lower hemoglobin F than non-hospitalized patients (12% vs. 17%, p = 0.02). For those who had access to vaccination at the time of infection, 25 out of 26 patients were adequately vaccinated and had mild disease. CONCLUSIONS: The SCD population is at higher risk of severe disease than the general population. However, we report favorable outcomes as no deaths occurred. Registries will continue to be critical to document the impact of novel COVID-19 specific therapy and vaccines for the SCD population.

ETAVOPIVAT TREATMENT FOR UP TO 12 WEEKS IN PATIENTS WITH SICKLE CELL DISEASE IS WELL TOLERATED AND IMPROVES RED BLOOD CELL HEALTH

Background: Etavopivat, an investigational, once-daily, selective, activator of erythrocyte pyruvate kinase (PKR) increases PKR activity, resulting in decreased 2,3-DPG and increased ATP in red blood cells (RBCs) of healthy volunteers and patients (pts) with sickle cell disease (SCD).1,2 Aims: We report results of an open-label (OL) extension cohort from a Phase 1 study (NCT03815695) designed to characterize the safety and clinical activity of etavopivat at a maximal pharmacodynamic dose in pts with SCD. Methods: 15 pts were enrolled to receive etavopivat 400 mg once daily for 12 wks, followed by a 4-wk follow-up. Assessments included safety, pharmacokinetics, pharmacodynamics, RBC health parameters and systemic markers of SCD pathophysiology. Results: Of 15 pts (age 32.3 ±10.1 yr;HbSS/SC n=13/2), 14 completed 12-wks of treatment (tx);1 pt discontinued tx after ∼2 wks. Etavopivat 400 mg once daily was generally well tolerated. Adverse events (AEs) reported during tx and follow-up were commonly low grade (Gr) and consistent with pts' SCD. Gr1-2 AEs in >2 pts (n [%]) were sickle cell pain events (9 [60%]);headache (5 [33%]);and upper respiratory tract infection (3 [20%]). The Gr3-4 AE in >1 pt was sickle cell vaso-occlusion (VOC;4 [27%]). On-tx serious adverse events (SAEs;1 pt each) were Gr3 VOC post Gr3 COVID (not tx-related) and Gr3 left femoral deep vein thrombosis (possibly related, resulting in tx discontinuation as stated above). SAEs (1 pt each) during the 4-wk follow-up were Gr3 acute chest syndrome + Gr3 VOC, Gr3 non-cardiac chest pain and Gr3 syncope (all unrelated). Observed increases in ATP and decreases in 2,3-DPG were durable over 12 wks of etavopivat tx. Etavopivat tx normalized hemoglobin (Hb)S-oxygen affinity to that of HbA. Etavopivat tx over 12 wks improved overall sickle RBC health, demonstrated by a reduction in point of sickling as well as improved measures of deformability and hydration of sickle RBCs (all P<0.01;Figure). Etavopivat tx over 12 wks was associated with a sustained significant increase in Hb compared with baseline (BL;P<0.0001), with mean maximal increase of 1.5 (range 0.7-2.3) g/dL. Ontx increase in Hb >1g/dL was achieved in 11 (73%) pts, for whom the mean maximal Hb increase was 1.8 (1.2-2.3) g/dL. Absolute reticulocytes, indirect bilirubin and lactate dehydrogenase significantly decreased from BL and were sustained over the 12wk period (all P<0.05), indicative of increased RBC lifespan and decreased hemolysis. Several markers of disease activity significantly decreased from BL during daily etavopivat tx, including the inflammatory marker tumor necrosis factor-α , which decreased by 35% (P<0.001). Based on preliminary exploratory analysis with an aggregate duration of etavopivat exposure of 3.32 pt-yrs in the OL cohort, a decrease in the trend for VOC Hospitalizations was observed: annualized historical and on-tx VOC Hospitalization rates were 0.93 and 0.30, respectively;the 1 on-tx VOC Hospitalization was COVID-related. Summary/Conclusion: Etavopivat 400 mg once daily for up to 12 wks demonstrated a tolerable safety profile and showed improvements in various markers of RBC health in pts with SCD. Rapid and sustained increases in Hb were associated with decreases in reticulocyte counts and markers of hemolysis, supporting increased sickle RBC lifespan and improved anemia. Together, these results support further evaluation of etavopivat in the Phase 2/3 Hibiscus Study (NCT04624659) currently enrolling pts. (Figure Presented).

High risk and low prevalence diseases: Acute chest syndrome in sickle cell disease.

INTRODUCTION: Acute chest syndrome (ACS) in sickle cell disease (SCD) is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of ACS in SCD, including diagnosis and management in the emergency department (ED) based on current evidence. DISCUSSION: ACS is defined by respiratory symptoms and/or fever and a new radiodensity on chest imaging in a patient with SCD. There are a variety of inciting causes, including infectious and non-infectious etiologies. Although ACS is more common in those with homozygous SCD, clinicians should consider ACS in all SCD patients, as ACS is a leading cause of death in SCD. Patients typically present with or develop respiratory symptoms including fever, cough, chest pain, and shortness of breath, which can progress to respiratory failure requiring mechanical ventilation in 20% of adult patients. However, the initial presentation can vary. While the first line imaging modality is classically chest radiograph, lung ultrasound has demonstrated promise. Further imaging to include computed tomography may be necessary. Management focuses on analgesia, oxygen supplementation, incentive spirometry, bronchodilators, rehydration, antibiotics, consideration for transfusion, and specialist consultation. Empiric antibiotics that cover atypical pathogens are necessary along with measures to increase oxygen-carrying capacity in those with hypoxemia such as simple transfusion or exchange transfusion. CONCLUSIONS: An understanding of ACS can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Acute chest syndrome and COVID-19 in hydroxyurea naïve sickle cell disease patient in a low resource setting.

Acute chest syndrome (ACS) is a severe complication of sickle cell disease (SCD) and one of the leading causes of mortality in SCD patients. The management of ACS is challenging and requires prompt intervention to halt clinical deterioration. With the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic, which also primarily results in acute respiratory illness, the clinical picture and treatment outcome in SCD patients with ACS remain unknown. We present a case of a 30-year-old male who came in with features of painful vaso-occlusive episode and haemolysis that later evolved to acute chest syndrome. Chest X-ray showed pneumonic changes and mild bilateral pleural effusion, and nasal Reverse Transcription-Polymerase Chain Reaction (RT-PCR) for COVID-19 test came out positive. He was managed supportively with simple transfusion, antibiotics, dexamethasone and oxygen support with a good clinical outcome. Presenting with non-specific symptoms and similar respiratory symptoms and signs, the clinical picture of COVID-19 can prove difficult to discern from that of ACS due to other causes. This report emphasizes a need for a higher index of suspicion whenever a SCD patient presents with symptoms of acute respiratory distress.

Sickle Cell Disease and COVID-19 Infection: Importance of COVID-19 Testing and Approach to Management.

Sickle cell disease is an autosomal recessive disorder resulting in the substitution of CTG by CAG in the sixth codon of the beta-globin gene. As a result of this, the hydrophilic glutamic acid residue is replaced by hydrophobic valine residue, leading to the formation of hemoglobin tetramer HBS. This alteration in the beta-globin chain makes the red blood cells prone to sickling, especially in the presence of risk factors such as stress, hypoxia, and infection. These sickled red blood cells have the tendency to adhere to the endothelium and lead to vessel occlusion and distal tissue ischemia. The recent coronavirus disease 2019 (COVID-19) outbreak has impacted millions across the globe, putting individuals with co-morbidities at particularly high risk, and patients with sickle cell disease are no exception. We present the case of a 47-year-old African American male presenting to the emergency department with subjective fevers and a two-day history of pain in the arms, legs, and chest. A diagnosed case of sickle cell disease, the patient was on hydromorphone for pain management but ran out of his medications a few weeks before presentation. On examination, the patient was saturating well with mild tenderness upon palpation of the arms, legs, and chest. On complete blood count, the patient had a hemoglobin of 11.3 g/dL and a white cell count of 13.1 x10(3)/mcL. The patient had a normal mean corpuscular volume with reticulocytosis, hypochromia, ovalocytosis, poikilocytosis, polychromasia, and target cells. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was positive. The chest X-ray did not reveal any significant findings. He was admitted to the medicine floor for the management of sickle cell crisis and was placed under airborne and droplet precautions. The patient was started on hydromorphone for pain management and intravenous fluid hydration. On the second day of admission, the patient reported increasing shortness of breath. He was saturating 90% on room air and 94% on 2 liters of supplemental oxygen. The white blood cell count increased to 18.42 x10(3)/mcL and the chest X-ray revealed reticular densities with patchy alveolar opacities in the left lung. Given the decline in respiratory status, the patient was started on remdesivir. Over the course of his hospital stay, the patient's pain and respiratory status improved, with the patient saturating 97% on room air. He was discharged home with instructions to follow isolation precautions for at least two weeks, folic acid, and adequate pain management. An appointment was also scheduled for the patient to follow with a sickle cell nurse practitioner upon discharge.

Favorable outcomes of patients with sickle cell disease hospitalized due to COVID-19: A report of three cases.

Sickle cell disease (SCD) is one of the most frequent and severe monogenic disorders, affecting millions of individuals worldwide. SCD represents a fatal hematological illness, characterized by veno-occlusive events and hemolytic anemia. Hemolytic anemia is caused by abnormal sickle-shaped erythrocytes, which induce parenchymal destruction and persistent organ damage, resulting in considerable morbidity and mortality. During the coronavirus disease 2019 (COVID-19) pandemic, patients with SCD were characterized as a 'high-risk' group due to their compromised immune system, caused by functional hyposplenism, as well as systemic vasculopathy. COVID-19 is characterized by endothelial damage and a procoagulant condition. The present study describes the clinical features, management and outcomes of 3 patients with SCD who were hospitalized due to COVID-19, who all had favorable outcomes despite the complications.

Diagnostic Challenge in a Sickle Cell Disease Patient with COVID-19

Acute chest syndrome is a life-threatening complication in sickle cell disease. Infections are frequently implied, and like other viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be a trigger. In addition, due to their inflammatory status, they may present a higher risk for severe coronavirus disease 2019 (COVID-19). Pneumonia and acute chest syndrome share clinical, laboratory, and radiological features and may overlap, which makes their differential diagnosis especially challenging. We describe a case of an adolescent with homozygous sickle cell disease that developed acute chest syndrome in the context of COVID-19. With it, we intend to bring awareness to the potential role of imaging in the differential diagnosis and in establishing the best approach for the patient. Chest computed tomography findings were suggestive of an alternative diagnosis to COVID-19 pneumonia and red cell transfusion, fluid management, analgesics, and antibiotics were administered with favorable outcome. © Author(s) (or their employer(s)) and Portuguese Journal of Pediatrics 2022.

Successful use of veno-venous extracorporeal membrane oxygenation for acute chest syndrome in a child with sickle cell disease and SARS-CoV-2.

Children with sickle cell disease (SCD) are at increased risk for severe illness due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the successful native lung recovery of a child with SCD referred for lung transplant (LTx) evaluation who was on prolonged veno-venous extracorporeal membrane oxygenation (VV-ECMO). He initially presented with acute chest syndrome complicated by SARS-CoV-2 infection that ultimately required dual-lumen, single bicaval VV-ECMO cannulation for respiratory support. Despite the increased risk of hemolysis and thrombosis from SCD and SARS-CoV-2 infection, he was successfully supported on VV-ECMO for 71 days without complications leading to native lung recovery with meticulous management of his SCD therapy. This report provides new insight on our approach to VV-ECMO support in a child with SCD and SARS-CoV-2 infection. With a successful outcome, the patient has returned home but still on mechanical ventilation with LTx still an option if he is not eventually liberated from invasive respiratory support.

Incidence of Sars-COV-2 Infection in Sickle Cell Patients Presenting with a Painful Crisis, a 12 Month Prospective Cohort Study

Background: Sickle cell disease (SCD) is frequently complicated by painful vaso-occlusive crises (VOCs) often resulting in healthcare utilization including hospital admission. A vaso-occlusive crisis (VOC) can be induced by multiple factors including infection, exposure to cold, physical exercise, dehydration and stress. Given the current SARS-CoV-2 pandemic, we hypothesized that SARS-CoV-2 (even without symptoms of upper airway infection) might play a major causal role in VOC. However, our data suggests that COVID-19 is not a frequent provoking factor for clinical VOCs during the pandemic. Methods: In order to test this hypothesis, consecutive SCD patients presenting to the emergency department in our centre with symptoms compatible with VOC between March 16 th 2020 and March 16 th 2021, were tested for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) of nasopharyngeal swabs irrespective of respiratory symptoms. Given the limited sensitivity of the RT-PCR in SARS-CoV-2 high incidence groups, low-dose non-contrast chest CT-scans were initially performed in addition to the RT-PCR.In addition, data comprised of temperature, oxygen saturation and laboratory results, was collected through chart review, from the visit at the emergency department. Presentations of SCD patients with a proven prior SARS-CoV-2 infection were excluded. Results: In total 122 VOCs in 70 adult SCD patients, presenting to the emergency department between March 16 th 2020 and March 16 th 2021, were evaluated. (Figure 1) Five presentations in two individual patients were excluded due to a prior RT-PCR proven SARS-CoV-2 infection. Furthermore, 13 presentations in six patients were excluded due to non-protocol adherence (not obtaining a RT-PCR at presentation). In total 104 episodes of VOC in 62 patients with SCD were prospectively analyzed on SARS-CoV-2 by RT-PCR irrespective of respiratory symptoms. In 104 consecutive presentations, five presentations tested positive on SARS-CoV-2 (4.8%). Only one of these five patients presented with respiratory symptoms in addition to the symptoms of a VOC and one patient was diagnosed with acute chest syndrome (ACS). Five of the 99 presentations of patients with a negative SARS-CoV-2 PCR, presented with respiratory symptoms. In this group, seven patients developed an ACS during admission. From March 16 th till May 31 st 2020, routine CT-scans were performed, in 23 out of 27 presentations with a VOC at the emergency department in addition to the RT-PCR in order to increase the diagnostic accuracy. In 19 of these presentations, that were tested negative for SARS-COV-2, no CT-abnormalities suggestive for COVID-19 were found. One of four CT-scans performed in patients with a positive RT-PCR, showed abnormalities that were not specific for COVID-19. Conclusion: In conclusion, we found a low incidence of SARS-CoV-2 infections in our cohort of consecutive SCD patients presenting with VOCs in 12 months during the COVID-19 pandemic. This suggests that COVID-19 is not a frequent provoking factor for clinical VOCs during the pandemic and may even be considered a coincidental finding given the low incidence and the fact that only one of the five patients with a positive RT-PCR presented with pulmonary symptoms. [Formula presented] Disclosures: Nur: Celgene: Speakers Bureau;Roche: Speakers Bureau;Novartis: Research Funding, Speakers Bureau.

Drepadom - Establishment of Home Care Services and Hospitalizations for Sickle Cell Disease Patients As Standard Care Since the Covid-19 Pandemic

INTRODUCTION Vaso-occlusive crisis (VOC), hallmark of sickle-cell disease (SCD), is the first cause of patients' emergency room (ER) admissions and hospitalizations. Acute chest syndrome (ACS) is a life-threatening complication that can occur during VOC and prolong hospitalization and is one of the main causes of death in SCD patients. The PRESEV score, established by team members and colleagues, assesses the risk of developing ACS (Bartolucci et al., 2016). In addition, the score has been validated by an international multicenter study, involving 13 centers, distributed in five different countries (PRESEV 2 - ASH 2020). Throughout the first wave of the Covid-19 pandemic, VOC management for SCD patients was a major concern. Our sickle cell referral center set up a hotline to monitor patients suffering from VOC daily, and organized the deployment of home-care services when required. The success of this system during the first wave of the pandemic led to the establishment of DREPADOM, a home-care and hospitalization protocol for VOC management in patients who are at a low risk of developing ACS, as standard care. DESCRIPTION OF SETTING Patients eligible for DREPADOM are patients that arrive at the ER for a VOC with a low PRESEV score, meaning low risk of developing ACS;or patients that are discharged early following hospitalization for VOC. After physical examination and calculation of the PRESEV score, DREPADOM home hospitalization is systematically offered to patients arriving to the ER with a PRESEV score ≤ 5. If the patient agrees, the DREPADOM nurse coordinator then acts as a link between the pharmacist, the oxygen supplier, the homecare provider, and the DREPADOM medical platform to activate the home hospitalization protocol. This entails the delivery of oxygen supply at the patient's house, dispatch of a medical prescription of opioids and parenteral treatments, twice/thrice-daily visits from homecare nurses, and an on-call SCD expert. DREPADOM relies on a system of daily telephone calls with three levels of expertise and warning and a decision-making algorithm. This is supervised by SCD experts, who arbitrate according to the evolution of the situation (stopping the follow-up, continuing the follow-up as an outpatient, hospitalization) (Fig.1). Furthermore, nurses enter patient vitals in real-time during their daily visits on a dedicated online platform (Link4Life) that contains an integrated automatic alert system. Additionally, a daily phone update between the DREPADOM coordination and the homecare provider's coordination concerning status and evolution of the patient's global condition takes place. RESULTS Over a 6-month period, 39 patients were included in the DREPADOM home hospitalization protocol, 3 of which were included multiple times for a total of 42 inclusions. Mean age was 40 years old [±9], sex ratio was 14/25 (male/female), ER vs early discharge ratio was 21/22, and mean homecare follow-up was 3 days (±1) for both, patients arriving from the ER and early discharge patients. Throughout the third wave of the pandemic, when hospital saturation was a major concern, patients with PRESEV scores 5 ≤ 11 were also offered DREPADOM. Three patients were hospitalized (7%): one for an ACS, who was included during the 3 rd wave of the pandemic with a PRESEV score of 8;one for pyelonephritis unrelated to the VOC;and one for difficulties with venous access. No death was reported. PERSPECTIVES Preliminary satisfaction surveys show a great enthusiasm for DREPADOM, partly due to the high standard of care received, but also due to the shorter length of hospitalization. In fact, median hospital stay for VOC is 4 [3-7] days (Bartolucci, 2016) whereas median homecare follow-up was 3 [1-6] days. [Formula presented] Disclosures: Bartolucci: Hemanext: Consultancy;Jazz Pharma: Other: Lecture fees;AGIOS: Consultancy;F. Hoffmann-La Roche Ltd: Consultancy;Emmaus: Consultancy;GBT: Consultancy;INNOVHEM: Other: Co-founder;Bluebird: Consultancy, Research Funding;Novartis: Consultancy, Membership on an entity's B ard of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding;Addmedica: Consultancy, Other: Lecture fees, Research Funding;Fabre Foundation: Research Funding.

COVID-19 and Sickle Cell Disease in the Province of Quebec: Morbidity and Mortality Rates Derived from the Provincial Registry

Introduction Approximately 1500 people live with sickle cell disease (SCD) in the province of Quebec, Canada. Public health has recognized these patients as immunocompromised. SCD patients may be at higher risk of developing severe COVID-19 infection due to their underlying pro-inflammatory and thrombogenic state, splenic dysfunction and secondary organopathies. Descriptions about disease severity and mortality rates in SCD vary widely. From the SECURE-SCD registry, Mucalo et al. recently reported a 0.3% and 4.7% mortality rate in children and adults, respectively. In the French registry, Arlet and colleagues reported a 2.4% death rate among those hospitalized with COVID-19 and SCD, not different from the general population. As a result, the COVID-19 morbidity and mortality rates among the SCD population remain uncertain. Objectives The primary objectives of our study are to describe the epidemiology, baseline characteristics and clinical outcomes of SCD patients with COVID-19 infection in the province of Quebec. In addition, we aim to identify risk factors for hospitalization and severe forms of COVID-19. Methods We built a web-based SCD-COVID-19 registry regrouping 7 adult and 4 paediatric tertiary care hospitals in the province of Quebec in June 2020. All SCD patients with a confirmed SARS-CoV-2 infection by PCR test were included in the study. We compared the prevalence of infection and hospitalization rates of SCD patients to the general population of Quebec using the epidemiological data from the INSPQ (National Institute of Public Health of Quebec) public database. We retrospectively analyzed data included between March 11, 2020 to March 1, 2021. Relative risk was calculated using bilateral association measures (exact fisher, mid-p or chi-squared tests, as appropriate) to compare the incidence of infection and hospitalization of SCD patients to the population of Quebec and to assess risk factors of hospitalization among SCD patients. Results During the first 12 months of the pandemic, 74 patients were included in the registry. The male to female ratio was 1:1.12. Median age was 23 years, ranging from 8 months to 68 years old. SS-Sbeta 0 genotypes were present in 51% of cases, while 49% were SC or Sbeta +. The majority of patients were on disease modifying therapy: 54% were on hydroxyurea and 17.5% on exchange transfusion therapy. The incidence of reported COVID-19 infection was significantly higher in SCD patients compared to the general population (4.9% vs. 3.5% p=0,002) (Table 1). Even more strikingly, SCD had rate of hospitalization 10-times greater than the general population (33.8 vs 3.2%, p<0,001). Nevertheless, the risk of admission to the intensive care unit was similar between SCD patients and the general population (24.0% vs. 24.1%, p=0.99). No death was recorded amongst SCD patients with COVID-19 compared to a death rate in the general population in Quebec of less than 70 years old of 48-78 for 100 000 infections (male-female). A history of acute chest syndrome (ACS) in the last year (OR 2.6 [1.5-4.6], p=0.04) and arterial hypertension (OR 3.3 [2.3-4.8], p=0.01) were associated with a higher risk of hospitalization (Table 2). On the other hand, there was no statistically significant association with age, sex, genotype, ABO blood group, baseline SCD therapy, or other comorbidities (chronic renal disease, obesity, pulmonary hypertension, chronic lung disease and previous admission to ICU) in our cohort. Conclusions Similar to other reports, we found that SCD patients were at much greater risk of hospitalization compared to the general population. We however found no increased risk of mortality or disease complication. This contrasts with results from other registries. A history of ACS and hypertension were associated with a higher risk of hospitalization. Whether social determinants of health could explain some of the outcome variability between different countries merit further investigation. Furthermore, we believe that registries are critical to monitor the impact of preventive measures. As vacci ation is ongoing, it will be important to consider its impact on hospitalization and death rate among SCD population. Recruitment to the registry is ongoing and updated data will be presented at the meeting. [Formula presented] Disclosures: Soulieres: BMS: Membership on an entity's Board of Directors or advisory committees;Novartis: Research Funding. Forté: Novartis: Honoraria;Canadian Hematology Society: Research Funding;Pfizer: Research Funding.

Sickle Cell Disease and COVID-19 Infection: A Single-Center Experience

Background and Objectives: The COVID-19 (CO19) pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics, and society. Several reports have shown that African Americans (AA) have been disproportionately affected by the CO19 pandemic. Limited data have suggested that sickle cell disease (SCD) could be one of the several reasons for higher morbidity and mortality related to CO19 among AA. Recent reports have suggested higher-than-average morbidity and mortality related to CO19 among patients with SCD. We conducted a retrospective, single-institution study in adult patients with SCD who were diagnosed with CO19 infection and their outcomes. Methods: After IRB approval, we conducted a chart review of adult patients (greater than 18 years) with SCD who were diagnosed with CO19 infection between March 1st, 2020, and March 31st, 2021. We recorded demographic data including age, gender, social factors (the type of insurance, availability of primary care provider (PCP), living alone/not), clinical parameters (type of SCD, co-morbidities), outpatient management of SCD, and how CO19 infection was managed like inpatient admission and complications. In patients who were admitted or seen in the emergency department (ED), we collected additional data including vitals, labs, the severity of illness, complications, length of stay, and outcomes. Computations were performed using statistical software SAS 9.4 for Windows. Results: We found a total of 51 patients with SCD diagnosed with CO19 infection in the above period. The median age of patients was 30 years. 61% were females and 39 % were males. All of them were AA. 11.76% were living alone, 49.02% were living with family, 1.96% (1 patient) was institutionalized, and the living situation was unknown in 37.25%. Most of the patients had Medicaid Insurance (52.94%), Medicare in 33.3%, private insurance in 13.73 % and 2% were uninsured. Only 64.71% of patients had a PCP. 60% had HbSS disease, 32% had HbSC disease, 4% had HbS-beta thalassemia, one patient each had HbSS with hereditary persistence of HbF and HbS/HbD. Comorbidities and previous history included acute chest syndrome in 65.96%, avascular necrosis in 36.96%, leg ulcers in 8.7%, hypertension in 8.7%, sickle cell retinopathy in 14.57%, cerebrovascular disease in 26.19%, chronic kidney disease in 7.69%, venous thromboembolism (VTE) in 20.41%, 10.41% were on anticoagulation, history of HIV and hepatitis C infection in 6.38%. 28.21% of patients were maintained on partial exchange transfusions as an outpatient for various indications. 72.73% were on hydroxyurea, 7.5% were on crizanlizumab, 5.26% were on voxelotor and 26.83% were on iron chelation. Vitals and pertinent lab values on initial assessment were recorded and many patients had missing data. On presentation, 25.53% were febrile, 29.17% of patients were tachycardic, 31.25% were hypoxic (SpO2 < 95%), 38.46% were tachypneic, 59.18% had a body mass index (BMI) of > 24.9. Median hemoglobin and hematocrit were 8.9/27.4 g/dL. The median white blood cell count was 9490/uL and platelets were 315,000/uL. Median ferritin was 1573 ug/L. Median bilirubin and creatinine were 2.05 mg/dL and 0.86 mg/dL. The patients were further stratified based on the clinical location where CO19 infection was managed (Table 1). 39.3% were diagnosed in the outpatient setting/ED and 60.3% in the inpatient setting. Among 51 patients, 5.71% (n=2) required ICU admission and was mechanically ventilated. 17.5% received dexamethasone, 7.69% received remdesivir, 2.76% received convalescent plasma, 17.07% had infections and 47% received antibiotics. Only one patient received an exchange transfusion during admission. One patient developed a new VTE after CO19 infection. On statistical analysis, the only factor which impacted the clinical location of management was tachycardia (P=0.007). Of the 51 patients, only 3.9% (2 patients) died of complications of CO19 infection, one with hypoxic respiratory failure, disseminated intravascular coagulation, shock, and the other one with pulmonary mbolism. 13% were readmitted within a month, one of them was admitted with a new pulmonary embolism and the others were admitted for acute painful episodes. Conclusion: We found a mortality rate of 3.9% in our single-center study of patients with SCD and CO19 infection. This mortality rate is lower than other published experiences in patients with SCD and CO19 infection. [Formula presented] Disclosures: Master: Blue Bird Bio: Current holder of individual stocks in a privately-held company.

A Fresh Breath of Oxygen: Red Blood Cell Exchange Transfusion in Sickle Cell and COVID-19.

Red blood cell exchange transfusion may be beneficial and should be considered in the early management of patients with sickle cell disease and COVID-19 to prevent the need for intubation and intensive care unit admission due to respiratory distress.

SARS CoV-2 infection in a patient with sickle cell disease - Atypical presentation.

Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection causes the disease known as coronavirus disease that started in Wuhan (China) in December 2019, leading to the current COVID-19 pandemic. The common presenting symptoms include fever, dry cough, shortness-of-breath, while sore throat, diarrhea, and abdominal and chest pain are the least. The atypical presentation of SARS CoV-2 infection poses a challenge for family physicians to screen and manage such patients for COVID-19 and specifically those at high risk with underlying disease such a sickle cell disease. Herein, we report a case of SARS CoV-2 infection in a known patient of sickle cell disease (SCD) with an atypical presentation, in whom the course of the disease was mild to moderate, uncomplicated, and the patient had an uneventful recovery. Primary care physicians should be vigilant to screen and manage such patients with established protocols, especially in the ongoing COVID-19 pandemic.