Celebrating the Sickle Cell Disease World Day on June 19th after Two Years of Pandemic: My Life with Scd, Patients' Perspective

Background: After two years of COVID in which activities were reduced due to the pandemic and each one's life was affected by restrictions and limitations, the Sickle Cell Disease (SCD) Association in Padova teamed up with the Sickle Cell Group at the Pediatric Hematology Oncology and Bone Marrow Transplant Unit to celebrate the Sickle Cell Disease world day by organizing an online meeting with children/youths and their families. Theme of the meeting was: "My Life with SCD: poems, pictures and writings express our view on disease and care". Aim(s): One of the goals of this meeting was to create an opportunity for individuals with SCD to meet and have a constructive discussion with each other about the disease and express their feelings after two years of pandemic. Method(s): One month before the meeting children, teenager and parents were asked to sharer with the organizing team any drawing, painting, poem, writing, that they felt could express their feelings or experience of the disease itself or how it affected their life, or their experience in the hospital. The materials received were organized in a power point presentation and At the meeting, families were able to see a PowerPoint presentation with the poems, drawings, writings. Each author had the choice to personally share their production or have it read out loud by a member of the team. Free time to comment or share experiences was given. Result(s): 20 children, teenagers and parents participated. Countries of origin (Nigeria, Ghana, Congo, Albania, Italy), religious background (catholic, muslim, no religion, other) were different as well as disease genotype (HbSS, HbSC, HbSBdegree), severity or treatment received (Hydroxyurea, transfusion, Hematopoietic stem cell transplantation -HSCT, none). Drawings and writings regarded experience with the disease (mechanism of action, admissions), feelings experienced (fear, hope, light at the end of the tunnel), aspirations (sports) and gratitude (to the social and medical team, to parents) (Figure 1). Surprisingly, families who had a child having undergone HSCT, reported on the need and importance to talk about this experience for years after the event and made a request of a support goup. Finally, all families underlined the need to meet again soon to discuss together issues related to personal experience with SCD, even via web. of discussion with each other and with the drepanocytosis group;and that throug the online telematics platform it is still possible to involve all families, listening and trying to comfort them on doubts and perplexities about the disease, In conclusion, it can be said that after two years of pandemic, in our setting, online meeting can help patients and families reconnect with each other and activities can be planned to aid experiences and feelings. Patients' associations and Health Care Teams can collaborate in this area.

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.

Kidney Transplantation in a Patient Affected by Sickle Cell Trait: A Case Report and State-of-the-Art Review.

Chronic kidney disease (CKD) is a common feature of sickle cell disease (SCD). The awareness of the clinical presentation and renal involvement in patients affected by hemoglobinopathies is greatly needed. Patient management is particularly complex, especially with kidney transplantation. We, therefore, report the case of a 56-year-old patient affected by sickle cell trait who underwent kidney transplantation. This case will underline all the various challenges the nephrologist must face in this clinical setting and their management.

Acceptability to and Engagement With a Virtual Sickle Cell Trait Education Program (SCTaware): Single-Center Prospective Study.

BACKGROUND: Public health programs are tasked with educating the community on health topics, but it is unclear whether these programs are acceptable to learners. Currently, these programs are delivered via a variety of platforms including in-person, virtually, and over the telephone. Sickle cell trait (SCT) education for parents of children with this trait is one of many education programs provided by the Ohio Department of Health. The novel SCTaware videoconference education program was developed by a research team after central Ohio's standard program transitioned from in-person to telephone-only education during the COVID-19 pandemic. OBJECTIVE: Our objectives were to investigate the acceptability of the format and engagement with the SCTaware education and assess parental worry about having a child with SCT before and after receiving SCTaware. METHODS: This was a single-center, prospective study of English-speaking parents of children <3 years of age identified to have hemoglobin S trait by newborn screening. Parents who previously received SCT education by telephone, were able to be contacted, and had access to an electronic device capable of videoconferencing were eligible to complete surveys after receiving the virtual SCTaware education program. The SCTaware educator also completed a survey to assess participant engagement. Data were summarized descriptively and a McNemar test was used to compare parental worry before and after receiving SCTaware. RESULTS: In total, 55 participants completed follow-up surveys after receiving standard SCT telephone education and then completing SCTaware. Most (n=51) participants reported that the SCTaware content and visuals were very easy to understand (n=47) and facilitated conversation with the educator (n=42). All of them said the visuals were respectful and trustworthy, helped them understand content better, and that their questions were addressed. Nearly two-thirds (62%, n=34) reported that the pictures appeared very personal and applied to them. The educator noted most participants (n=45) were engaged and asked questions despite having to manage distractions during their education sessions. Many participants (n=33) reported some level of worry following telephone-only education; this was significantly reduced after receiving SCTaware (P<.001). CONCLUSIONS: Our results suggest that SCTaware is acceptable and engaging to parents. While telephone education may make SCT education more accessible, these findings suggest that many parents experience significant worry about their child with SCT after these sessions. A study to evaluate SCTaware's effectiveness at closing parents' SCT knowledge gaps is ongoing.

An Unusual Presentation of Rhabdomyolysis and Acute Kidney Injury after Physical Activity: A Case Report.

Exercise-induced rhabdomyolysis refers to the breakdown of striated muscle, which releases intracellular elements into the bloodstream due to heavy physical activity. In rare instances, this condition may be the first clinical manifestation of sickle cell trait (SCT). We report on a 31-year-old woman with post-infectious fatigue who, after suffering mild COVID-19 symptoms 3 weeks prior, presented with intense muscle pain in the ankles, dyspnea, and choluria hours after strenuous physical exercise during a practical test. She sought emergent care the next day, where serum creatinine was measured at 2.4 mg/dL (baseline 1.0 mg/dL) and creatine phosphokinase at 118,000 U/L. She was previously healthy, without regular use of any medication, and habitually sedentary except in training, with no personal or family history of blood or muscle diseases. She was admitted without hemodialysis and discharged after 2 weeks. At 3 months, she had normalization of creatine phosphokinase and creatinine. As an outpatient, other tests were requested. Hemoglobin (Hb) electrophoresis revealed HbA1 of 57.8%, HbA2 of 3.1%, HbF of 0.3%, and HbS of 38.8%, which were compatible with SCT. Evaluation for SCT should be considered in cases of exercise-induced rhabdomyolysis, especially in young, healthy patients.

A CASE OF BORDETELLA BRONCHISEPTICA AND PNEUMOCYSTIS JIROVECI PNEUMONIA IN A YOUNG PATIENT

SESSION TITLE: Procedures in Chest Infections Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Pneumonia is a common condition that is seen in hospitals. Pneumocystis Jirovecii is an opportunist fungal pathogen. Bordetella bronchiseptica is a gram negative bacteria that causes infectious bronchitis in dogs and other animals, but rarely infects humans. CASE PRESENTATION: Patient is a 34 year old African American female with history of sickle cell trait, reported Lupus (not on treatment), asthma, COVID pneumonia who was admitted for worsening shortness of breath & productive cough with yellow sputum. She was previously hospitalized and discharged after being treated for Community-Acquired Pneumonia. In the ER, she was febrile, tachycardic, tachypneic, & hypoxic requiring BiPAP. CXR obtained showed findings concerning for multifocal pneumonia. Chest CT Angiogram was negative for PE. Patient was started on Vancomycin & Meropenem for treatment of her pneumonia. Blood cultures, Legionella, Strep pneumoniae, Aspergillus, Beta-D-glucan, Sputum culture, & MRSA screen were ordered for further evaluation of her infection. ANA screen reflex panel, lupus anticoagulant, anticardiolipin antibodies, beta-2 glycoprotein antibodies were also ordered given patient's reported history of SLE and the concern for SLE pneumonitis: ANA & Sjogren's Anti-SSA were positive;otherwise, autoimmune workup was unremarkable. During hospitalization, patient was eventually weaned down to nasal cannula and antibiotic was de-escalated to levaquin. However, sputum culture eventually grew Bordetella Bronchiseptica that was resistant to Levaquin so antibiotic regimen was switched to Doxycycline. In addition, Beta-D-glucan was noted to be elevated. Bronchoscopy was done for further evaluation;multiple transbronchial biopsies were positive Pneumocystis Jirovecii. Patient was then initiated on Bactrim for treatment of PJP Pneumonia along with a steroid taper. Patient was tested for HIV and it was negative. DISCUSSION: In this case, patient was found to have two rare pathogens, that are more common in immunocompromised patients such as those with HIV/AIDS, on high-dose corticosteroids or malignancy. This patient had a unconfirmed diagnosis of SLE and past COVID Pneumonia. Patient had Bordetella bronchiseptica pneumonia that is frequently isolated in the respiratory tract of animals but can cause severe respiratory infection in humans. This microorganism can cause upper respiratory tract infections, pneumonitis, endocarditis, peritonitis, meningitis, sepsis and recurrent bacteremia. Upon further discussion with the patient, she was found to have a recent pet dog. CONCLUSIONS: High level of clinical suspicious is needed in patient presenting with recurrent pneumonia with chest imaging findings suggestive of multifocal pneumonia. The mainstay of treatment for PJP is TMP-SMX and steroid. We recommend Fluoroquinolones or tetracycline for Bordetella bronchiseptica pneumonia. Reference #1: Benfield T, Atzori C, Miller RF, Helweg-Larsen J. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review. J Acquir Immune Defic Syndr. 2008 May 1;48(1):63-7. Reference #2: de la Fuente J, Albo C, Rodríguez A, Sopeña B, Martínez C. Bordetella bronchiseptica pneumonia in a patient with AIDS. Thorax. 1994 Jul;49(7):719-20. doi: 10.1136/thx.49.7.719. PMID: 8066571;PMCID: PMC475067. DISCLOSURES: No relevant relationships by Priya George No relevant relationships by ELINA MOMIN No relevant relationships by Mohammedumer Nagori

Critical leg ischemia related to COVID 19 in doubly vaccinated patients

Background: COVID and venous thromboembolism in unvaccinated population is now a well-established entity but this case is unique as the 1) patient had both COVID vaccines and then tested positive for COVID and 2) presented with vague symptoms and had minimum oxygen requirement 3) developed arterial thromboembolism and acute leg ischemia after 4 days of admission leading to limb amputation ultimately. Data on COVID and COVID vaccine's association with Arterial thromboembolismstill needs to be explored. In our case it was challenging to establish whether the thromboembolism was a complication of vaccine, COVID or was that the result of synergistic interaction of both. Case Presentation: 61 Years old gentleman presented to Emergency Department with vague history of lethargy ongoing for 3-4 weeks and no significant prior co-morbid except sickle cell trait. He had received both doses of COVID vaccine 2 months before presentation and denied any shortness of breath, cough, fever or pain. On presentation he was de-saturating to 77% on Room air and had bilateral crepitations in his chest with PO2 of 7.4 kPa on ABG and raised inflammatory markers on bloods. His CXR showed changes consistent with COVID and he was started on Dexamethasone. His COVID test came back as positive. Throughout his staymaximumamount of oxygen required by him was 36% day1 which improved to 28-32% later, he had not been tachypneic or tachycardiac. His d-dimer was raised at 3000 which was thought to be COVID related, and the decision was taken to perform CTPA to rule out Pulmonary embolism if oxygen requirement worsens. His oxygen requirement continued to remain static with a little improvement or worsening. His inflammatory markers also got better. On Day 4 Patient complained of Right Leg pain. On further enquiry he revealed pain has been ongoing for last 2-3 weeks. His legs were bilaterally ice cold to touch and had hair loss in bilateral legs, pulses in both legs down the femoral artery were not palpable bilaterally. His blood gas Lactate was 2.6 with worsening inflammatory markers but no fever spikes or worsening in oxygen requirement or any other symptoms apart from leg pain. He was immediately seen by vascular Surgery team and was started on therapeutic anticoagulation suspecting acute leg ischemia. CT Angio report showed: Occlusion of Right iliac system, common femoral artery part of the SFA and all the popliteal artery and tibial vessels and unstable thrombus in the left common iliac artery causing severe stenosis and occluded left TP trunk. He was continued on therapeutic anticoagulation and then underwent Right iliofemoral embolectomy, on table angiogram, left common iliac angioplasty via left groin approach and right above knee amputation. Postoperatively he remained well and was tested COVID negative later. He was then discharged to Rehab from hospital for further care. Discussion and conclusion: We suggest that COVID patients with significantly raised d-dimers should be investigated for hidden thromboembolic focus in same way in non COVID patients and not just in lungs but in other organ systems as well. There should be some guidelines regarding increased dose prophylaxis or a flowchart to investigate for these thromboembolic association in COVID.

COVID-19 outcomes in sickle cell disease and sickle cell trait.

Throughout the Coronavirus Disease 2019 (COVID-19) pandemic, understanding the effects of COVID-19 on persons with Sickle Cell Disease (SCD) and Sickle Cell Trait (SCT) has garnered interest. Patients with SCD diagnosed with COVID-19 utilize the emergency department and are hospitalized at significantly higher rates compared to the general population, with vaso-occlusive crisis and acute chest syndrome as the leading presentations. Whether SCD alone increases the likelihood of severe COVID-19 illness remains uncertain; however, potential risk factors for severe disease among patients with SCD include older age, frequent acute care visits for pain, haemoglobin SC disease, and pre-existing end-organ disease. SCT status may also influence COVID-19 outcomes, particularly among those with pre-existing co-morbidities. Corticosteroids in patients with SCD and COVID-19 should be used with extreme caution given strong associations between corticosteroid exposure and severe vaso-occlusive crisis, with prophylactic transfusion administered if corticosteroids are deemed necessary. Hydroxyurea may be protective in COVID-19.

Sudden cardiac death in the pediatric and adolescent population

Each year nearly 7,000 children, adolescents, and young adults in the United States as well as tens of thousands worldwide die unexpectedly. Nearly 50% of these deaths occur with little or no warning. This discussion reviews the epidemiology, presentation, diagnosis, and management of sudden cardiac death (SCD). SCD is predominantly due to previously unrecognized structural abnormalities of the heart and underlying or acquired conditions that predispose persons, especially when involved in exercise, to sudden death. Topics considered include SCD presenting signs, symptoms, diagnoses, and when applicable, management of common conditions associated with SCD.

COVID-19 in Patients with Hematologic-Oncologic Risk Factors: Complications in Three Patients

The novel COVID-19 infection has demonstrated a spectrum of complications involving vascular, inflammatory, infectious, and metabolic conditions. These complications range from mild loss of smell to more severe acute respiratory distress syndrome (ARDS). Patients with more severe complications often require sedation and mechanical ventilation. Growing research has revealed the role of active malignancy and disease-in-remission status as possible risk factors contributing to the morbidity and mortality inCOVID-19 patients. In our descriptive case series, we present three unique cases of complicated COVID-19 infection in patients with hematologic-oncologic risk factors and review the imaging features of their complications. The first patient was a 33-year-old male with sickle cell trait who developed rhabdomyolysis and myonecrosis of the paraspinal muscle in the setting of a physical fitness test;he subsequently developed an abscess at this site, presumably exacerbated by the hypoxemic state of his COVID-19 pneumonia. Our second patient was a 37-year-old male with COVID-19 pneumonia and a history of stage IV Non-Hodgkin's lymphoma in remission who developed spontaneous pneumomediastinum in the absence of positive pressure ventilation. The third COVID-positive patient was a 54-year-old male with a past medical history significant for grade 1 follicular non-Hodgkin's lymphoma in remission with sputum culture positive for mycobacterium avium complex and bronchoscopy positive for candida growth. 18-FDG/PET imaging was performed and demonstrated diffuse intense uptake throughout the lungs reflecting both the COVID-19pneumonia and the multimicrobial superinfection.

ECAST Syndrome (Exercise Collapse Associated with Sickle Cell Trait): First Knock of Sickle Cell in a Young Bodybuilder

ECAST Or exercise collapse associated with sickle cell trait is a rare phenomenon associated with sickle cell trait and is an important presentation of sickle cell disease in sports medicine. Collapse is seen following vigorous physical activity, which is due to excessive heat, dehydration and other factors associated with physical exercise. This rare syndrome is often missed by the treating physicians as a result of a lack of knowledge about this rare entity leading to massive underreporting. It is important to identify ECAST as a cause of the collapse in young athletes to prevent mortality and morbidity and in order to provide prompt treatment. We report a case of a 25-year-old young male who was a bodybuilder and reported to the gym after a one-year-long break due to lockdown restrictions of COVID19. After a vigorous exercise session, he collapsed in the gym and was brought to the emergency department. After proper history taking and examination, he was suspected to be a case of ECAST due to a history of a similar episode three years back which was treated as a case of exertional syncope with intravenous fluid therapy and a family history of Sickle cell trait with his mother and father both having sickle cell AS Pattern. Ultimately our patient turned out to be a case of Sickle Cell Trait with evidence of AS pattern on Hb electrophoresis and a small-sized spleen visualized on CT Scan of the abdomen. The patient was managed successfully with intravenous fluids and blood transfusion and was discharged in a stable condition. He was counseled about moderating his exercise and is doing well on follow-up.

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.

Venous Thromboembolism Post-COVID-19 Among Individuals with Sickle Cell Disease

Background: Individuals with sickle cell disease (SCD) are at risk of severe COVID-19 infection. Those with SCD are also known to be at risk of venous thromboembolism (VTE), with numerous mechanistic pathways likely at interplay. In general, prior studies indicate that COVID-19 infection is associated with a thromboembolic risk. However, it is unknown if COVID-19 infection increases the already high risk of VTE for individuals with SCD. Given the preexisting risk for thrombophilia associated with SCD, we hypothesized that COVID-19 infection would further increase the risk of a venous thromboembolic event. In this study, we leverage electronic health record data to determine, at a population level, whether individuals with SCD hospitalized for COVID-19 have higher VTE rates when compared to hospitalization for any other cause. Method: Using electronic health record data from a multisite research network, TriNetX (years 2010 - 2020) we identified two mutually exclusive cohorts of individuals with SCD between Jan 20, 2020 - Dec 31, 2020: 1) those with hospitalizations related to a diagnosis of COVID-19 and 2) those with hospitalization for other causes. COVID-19 related hospitalizations were defined as admissions occurring within a month of COVID-19 diagnosis. Overall, individuals were considered to have SCD if they had 3 or more instances of ICD coding for SCD during the time frame of years 2010 - May 20, 2021 and did not have any ICD code for sickle cell trait. The outcome of interest was VTE, which included either deep venous thrombosis (DVT), pulmonary embolism (PE) or both. We determined the VTE rates at 1 month, 3 months and 6 months post hospitalization. The VTE rates between the two groups were compared using measures of risk difference and risk ratios, along with the respective 95% confidence intervals. We also matched the groups using propensity scores based on the prevalence of VTE prior to the index event of hospitalization and compared the respective outcomes. Results: Within the TriNetX network, there were 223 (59% females) individuals with SCD hospitalized due to COVID-19, and 3,591 (54% females) hospitalized for causes other than COVID-19. Individuals with SCD hospitalized for COVID-19 were older than individuals with SCD hospitalized for other causes (mean age: 29.4 yrs, sd = 16.4 vs 26.3 yrs, sd = 16.8, p value = 0.006). A significantly higher proportion of individuals hospitalized for COVID-19 had a prior history of portal vein thrombosis (4% vs ~0%, p-value <0.001), phlebitis/thrombophlebitis (4% vs 2%, p-value = 0.026) and other VTE (16% vs 10%, p-value = 0.008). There were no significant differences in sex or proportion of those with prior history of PE between the two groups. Table 1 shows the VTE rates observed in the two groups 1, 3 and 6 months post-hospitalization, respectively. VTE rates were higher among individuals with SCD hospitalized for COVID-19 than among individuals with SCD hospitalized for other causes. After matching for previous history of VTE, individuals with SCD hospitalized for COVID-19 infection did not have significantly higher VTE rates compared to individuals with SCD hospitalized for other causes at any of the time points evaluated. Conclusions: These data suggest that immunothrombosis accompanying SARS-COV-2 infection in individuals with SCD does not exacerbate the underlying known thrombophilia associated with SCD and provide support for current clinical guidelines in this population. Future prospective studies controlled for anticoagulant therapy exposures may provide more direct evidence to guide thromboprophylaxis in this unique population. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Blackwater Fever in Pregnancy With Severe Falciparum Malaria: A Case of Imported Malaria From Nigeria to the United Kingdom During the COVID-19 Pandemic.

We present the case of imported malaria in pregnancy to the United Kingdom (UK) from Nigeria, where a 28-year-old primigravida presented to our maternity assessment unit (MAU) with complaints of pyrexia, rigors and passing dark coloured urine. She gave a travel history of recent migration from Nigeria 10 days before presenting to our emergency department. She initially became unwell five days after her arrival with general malaise and myalgia. On day six, she developed lower abdominal pain and observed that her urine was dark in colour. This prompted her to contact her general practitioner (GP). Treatment for a urinary tract infection was initiated by the GP after a phone consultation in keeping with COVID-19 contingency guidance, and the patient was prescribed antibiotics for three days. She presented to the emergency department two days after completing the course of antibiotics where she complained of worsening pelvic pain, reduced foetal movements and passing black urine. She was treated as suspected COVID-19 and red flag sepsis. Obstetric review led to investigation and diagnosis of severe malaria in pregnancy, which was accompanied by blackwater fever (BWF). The patient recovered after three doses of artesunate. An ultrasound scan of the foetus revealed a congenital cardiac anomaly, which had not been detected in an earlier scan. There was no evidence of congenital malaria in the neonate after delivery. There are several novel aspects in this case as maternal mortality in severe Plasmodium falciparum can be significantly high. Those who survive the disease in pregnancy are also known to develop several complications such as intrauterine death and preterm labour. There was also the component of blackwater fever, which is a rare event associated with severe malaria, and it also has a mortality rate. Significant in her medical history was a diagnosis of the sickle cell trait, and we postulate that this feature gave an added protection from the complications of severe malaria in pregnancy as well as blackwater fever.

Adult onset PIMS-TS with secondary haemophagocytic lymphistiocytosis: Into the eye of the cytokine storm

Case report-IntroductionA small sub-group of COVID-19 patients develop secondary haemophagocytic lymphohistiocytosis (sHLH), a multisystem progressive hyperinflammatory syndrome characterised by fever, hepatosplenomegaly, hyperferritinaemia, cytopenia, and multiple-organ failure, which if not identified and promptly treated may be fatal. There have been isolated reports of adults developing PIMS-TS, a rare inflammatory multisystem syndrome seen in children with COVID-19 which shares common features with Kawasaki disease, toxic shock syndrome and macrophage activation syndrome/sHLH. Here we present a case of COVID-19-associated PIMS-TS in an adult complicated by frank sHLH (COV-HLH) which, after a protracted course, responded to combination immunotherapy including the IL-1 antagonist anakinra.Case report-Case descriptionA 22-year-old female of Nigerian-descent with sickle cell trait presented with fever, headache, sore throat, arthralgia, abdominal pain, diarrhoea/vomiting, swollen feet/legs, and macular rash on hands/forearms. A 3-day flu-like illness occurred 8 weeks earlier. Persistent pyrexia, tachycardia and hypotension required ICU admission for inotropic support. Although she briefly required oxygen, hypoxaemia was not a prominent feature. Bloods revealed CRP>200mg/L, ferritin<14,000ng/mL, raised D-Dimer, procalcitonin, Troponin-T and ALT, anaemia, lymphopenia, and neutrophilia. Computed-tomography showed mild bibasilar subpleural ground-glass changes, pelvic free fluid, and peritoneal enhancement. As treatment for suspected COV-HLH, or connective tissue disorder, intra-venous hydrocortisone 100mg QDS was given;fever resolved and blood parameters transiently improved. Second nasopharyngeal SARS-CoV-2 RT-PCR was positive and screen for other infection and autoimmune disease negative. Echocardiography and CTA excluded coronary aneurysms although Troponin-T peak was 330ng/L.Rapidly rising ferritin and triglycerides, falling cell counts and fibrinogen, led to a diagnosis of COV-HLH. Intra-venous anakinra 70mg (1mg/kg) BD was initiated. When pyrexia remained >40 °C, inotrope requirement persisted, cell counts fell and ferritin rose to 45,861ng/ml, anakinra was increased over 48h to 200mg BD with intra-venous methylprednisolone 1g OD x2. After 7 days anakinra was weaned to 100mg subcutaneous BD enabling discharge. Outpatient bone marrow aspirate/trephine showed reactive hyperplasia, no leukaemia or haemophagocytosis. Genomic testing showed no primary genetic cause. A week later she was readmitted with fatigue, arthralgia, pyrexia, tachycardia, haematuria, and ferritin of 23,000ng/mL (nadir 4,000ng/mL). FDG-PET showed hepatosplenomegaly with no lymphoma. Anakinra was increased to 200mg IV BD with IVIG 1mg/kg OD x2 and methylprednisolone 1g IV OD x3, then cyclosporine 1mg/kg IV BD. Fevers and haemoproteinuria resolved within 1 week and inflammatory markers fell allowing discharge on a reducing regime of subcutaneous anakinra, oral prednisolone and cyclosporine. She remained well;ferritin and FBC finally normalised >2 months after presentation.Case report-DiscussionThrough the UK HLH across speciality collaboration (HASC) we are aware of only a handful of UK cases of adult presentation PIMS-TS and even fewer with frank sHLH. Our patient's ethnic background and presentation were typical for paediatric PIMS-TS. Hence, we actively excluded coronary artery aneurysms, a key feature of the Kawasaki-type variant of PIMS-TS.Initial COVID-19 swabs were negative as was extensive investigation for other sepsis triggers. A high clinical suspicion of COVID-19 led to the second positive swab and early recognition of sHLH. Diagnosis of HLH can be challenging due to its non-specific features and was even more difficult in critically ill patients during the peak of the pandemic, where bone marrow biopsy and cross-sectional imaging (key components of diagnostic scoring systems such as the HScore) were difficult to obtain. Persistent pyrexia, hyperferritinaemia and recognition of worsening trends in all relevant domains raised suspic on of sHLH. On initiation of anakinra, her HScore was only 118, although her illness peak was 162, well above the HASC agreed threshold of 132 for HLH diagnosis during the pandemic. She subsequently had a negative bone marrow biopsy in line with >50% of critical care patients with sHLH;a demonstration that biopsy proven haemophagocytosis is not necessary for a clinical diagnosis of sHLH. No other sHLH trigger was found.Early recognition and intensive treatment may have contributed to the positive outcome;sHLH mortality in ICU patients can reach nearly 70%. These decisions were facilitated by early discussion with MDT members of HASC. The initial dose of 70mg IV BD and speed of wean after an effective dose was achieved were insufficient. A longer period on 400mg anakinra daily, a slower wean, plus addition of methylprednisolone, IVIG and cyclosporin appeared to aid the resolution of her relapse. Case report-Key learning points COVID-19 infection is complicated by hyperinflammatory syndromes (cytokine storm, PIMS-TS, sHLH) in a significant minority of patients. In the absence of a treatment for COVID-19, early recognition of treatable complications should be a clinical priority.Adult clinicians should be aware of PIMS-TS which may rarely occur in young adults, especially those of African descent. The CDC definition extends to those aged up to 21. Cardiac aneurysms should be actively excluded in this group.The challenges associated with sHLH diagnosis became more apparent during the peak of the COVID-19 pandemic where key tests were difficult to obtain. Current scoring systems are insensitive for evolving sHLH. A high index of clinical suspicion and a multidisciplinary team approach, in which rheumatologists are key, is important for early recognition and treatment. Although no other sHLH trigger was found in this case, we have seen COV-HLH patients with underlying connective tissue disorder, haematological malignancy or a primary genetic defect, which should be considered if COV-HLH patients do not respond to treatment.Optimal treatment for sHLH and the hyperinflammatory syndromes associated with COVID-19 is not supported by randomised controlled trials but there is accumulating evidence for anakinra. Whilst its use in sHLH remains off-license, UK guidelines have been developed, with an emphasis on early and high dose treatment. Careful anakinra weaning regimens should be considered and patient progress regularly reviewed to avoid relapse of sHLH and subsequent readmission. Our patient also appeared to have a favourable response to corticosteroid and other combined immunosuppressive treatments including IVIG and cyclosporine. It remains to be seen if the incidence of adult-onset PIMS-TS and COV-HLH will reduce now that Dexamethasone is standard of care in adult patients with COVID-19.

Clinical outcomes of COVID-19 in patients with sickle cell disease and sickle cell trait: A critical appraisal of the literature.

Individuals with sickle cell disease (SCD) and sickle cell trait (SCT) have many risk factors that could make them more susceptible to COVID-19 critical illness and death compared to the general population. With a growing body of literature in this field, a comprehensive review is needed. We reviewed 71 COVID-19-related studies conducted in 15 countries and published between January 1, 2020, and October 15, 2021, including a combined total of over 2000 patients with SCD and nearly 2000 patients with SCT. Adults with SCD typically have a mild to moderate COVID-19 disease course, but also a 2- to 7-fold increased risk of COVID-19-related hospitalization and a 1.2-fold increased risk of COVID-19-related death as compared to adults without SCD, but not compared to controls with similar comorbidities and end-organ damage. There is some evidence that persons with SCT have increased risk of COVID-19-related hospitalization and death although more studies with risk-stratification and properly matched controls are needed to confirm these findings. While the literature suggests that most children with SCD and COVID-19 have mild disease and low risk of death, some children with SCD, especially those with SCD-related comorbidities, are more likely to be hospitalized and require escalated care than children without SCD. However, children with SCD are less likely to experience COVID-19-related severe illness and death compared to adults with or without SCD. SCD-directed therapies such as transfusion and hydroxyurea may be associated with better COVID-19 outcomes, but prospective studies are needed for confirmation. While some studies have reported favorable short-term outcomes for COVID-19 patients with SCD and SCT, the long-term effects of SARS-CoV-2 infection are unknown and may affect individuals with SCD and SCT differently from the general population. Important focus areas for future research should include multi-center studies with larger sample sizes, assessment of hemoglobin genotype and SCD-modifying therapies on COVID-19 outcomes, inclusion of case-matched controls that account for the unique sample characteristics of SCD and SCT populations, and longitudinal assessment of post-COVID-19 symptoms.

COVID-19 in Patients With Hematologic-Oncologic Risk Factors: Complications in Three Patients.

The novel COVID-19 infection has demonstrated a spectrum of complications involving vascular, inflammatory, infectious, and metabolic conditions. These complications range from mild loss of smell to more severe acute respiratory distress syndrome (ARDS). Patients with more severe complications often require sedation and mechanical ventilation. Growing research has revealed the role of active malignancy and disease-in-remission status as possible risk factors contributing to the morbidity and mortality in COVID-19 patients. In our descriptive case series, we present three unique cases of complicated COVID-19 infection in patients with hematologic-oncologic risk factors and review the imaging features of their complications. The first patient was a 33-year-old male with sickle cell trait who developed rhabdomyolysis and myonecrosis of the paraspinal muscle in the setting of a physical fitness test; he subsequently developed an abscess at this site, presumably exacerbated by the hypoxemic state of his COVID-19 pneumonia. Our second patient was a 37-year-old male with COVID-19 pneumonia and a history of stage IV Non-Hodgkin's lymphoma in remission who developed spontaneous pneumomediastinum in the absence of positive pressure ventilation. The third COVID-positive patient was a 54-year-old male with a past medical history significant for grade 1 follicular non-Hodgkin's lymphoma in remission with sputum culture positive for mycobacterium avium complex and bronchoscopy positive for candida growth. 18-FDG/PET imaging was performed and demonstrated diffuse intense uptake throughout the lungs reflecting both the COVID-19 pneumonia and the multimicrobial superinfection.

Impact of COVID-19 Infection on 24 Patients with Sickle Cell Disease. One Center Urban Experience, Detroit, MI, USA.

The city of Detroit has a large population of individuals with sickle cell disease, and hospitals in Detroit have seen some of the highest numbers of cases of coronavirus disease-19 (COVID-19) in 2020. The purpose of this study was to examine the pathophysiological characteristics of COVID-19 in patients with sickle cell disease or trait to determine whether these patients have unique manifestations that might require special consideration. This retrospective analysis included 24 patients with confirmed COVID-19 and sickle cell disease or trait who were seen at the Henry Ford Hospital, Detroit, MI, USA, between March 1 and April 15 2020. Of the 24 patients, 18 (75.0%) had heterozygous sickle cell trait, one (4.0%) was a double heterozygote for Hb S (HBB: c.20A>T)/ß+-thalassemia (ß+-thal), four had sickle cell anemia (ßS/ßS) and one (4.0%) had Hb S/Hb C (HBB: c.19G>A) disease. A total of 13 (54.0%) patients required hospitalization. All four patients with sickle cell anemia, developed acute pain crisis. We observed one patient who developed acute pulmonary embolism and no patients developed other sickle cell associated complications. Additionally, three (13.0%) patients required packed red blood cell transfusion without the need of exchange transfusion, and one patient required admission to the intensive care unit (ICU), mechanical ventilation and subsequently died. Patients with sickle cell disease or trait and laboratory-confirmed COVID-19 had a generally mild, or unremarkable, course of disease, with lower chances of intubation, ICU admission and death, but with a slightly longer hospitalization.

Sickle cell trait and the potential risk of severe coronavirus disease 2019-A mini-review.

Coronavirus Disease 2019 (COVID-19) pandemic is a rapidly evolving public health problem. The severity of COVID-19 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID-19 among African Americans, although detailed epidemiological study data is pending. Sickle cell disease (SCD) disproportionately affects Black/African Americans in the United States as well as forebearers from sub-Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America), and some Mediterranean countries. The carrier frequency for SCD is high among African Americans. This article underscores the putative risks that may be associated with COVID-19 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine.