Blocking HbS Polymerization in SCD.

Sickle cell disease (SCD) is caused by a point mutation in the ß-globin gene that creates hemoglobin S (HbS). Upon deoxygenation, HbS forms long polymers that distort the shape of red blood cells, causing hemolysis and vaso-occlusion. Voxelotor inhibits HbS polymerization, the root cause of SCD complications. To view this Bench to Bedside, open or download the PDF.

Hydroxyurea reduces infections in children with sickle cell anemia in Uganda.

ABSTRACT: After starting hydroxyurea treatment, Ugandan children with sickle cell anemia had 60% fewer severe or invasive infections, including malaria, bacteremia, respiratory tract infections, and gastroenteritis, than before starting hydroxyurea treatment (incidence rate ratio, 0.40 [95% confidence interval, 0.29-0.54]; P < .001).

Hydroxyurea treatment is associated with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa.

Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) provides hydroxyurea at maximum tolerated dose (MTD) for children with sickle cell anemia (SCA) in sub-Saharan Africa. Beyond reducing SCA-related clinical events, documented treatment benefits include ∼50% reduction in malaria incidence. To identify associations and propose mechanisms by which hydroxyurea could be associated with lower malaria rates, infections were recorded across all clinical sites (Angola, Democratic Republic of Congo, Kenya, and Uganda). Hazard ratios (HR) with 95% confidence intervals (CIs) for baseline demographics, and time-varying laboratory and clinical parameters were estimated in a modified Cox gap-time model for repeated events. Over 3387 patient-years of hydroxyurea treatment, 717 clinical malaria episodes occurred in 336 of 606 study participants; over half were confirmed by blood smear and/or rapid diagnostic testing with 97.8% Plasmodium falciparum. In univariate analysis limited to 4 confirmed infections per child, malaria risk was significantly associated with absolute neutrophil count (ANC), splenomegaly, hemoglobin, and achieving MTD; age, malaria season, MTD dose, fetal hemoglobin, α-thalassemia, and glucose-6-phosphate dehydrogenase deficiency had no effect. In multivariable regression of confirmed infections, ANC was significant (HR, 1.37 per doubled value; 95% CI, 1.10-1.70; P = .0052), and ANC values <3.0 × 109/L were associated with lower malaria incidence. Compared with nonpalpable spleen, 1- to 4-cm splenomegaly also was associated with higher malaria risk (HR, 2.01; 95% CI, 1.41-2.85; P = .0001). Hydroxyurea at MTD is associated with lower malaria incidence in SCA through incompletely defined mechanisms, but treatment-associated mild myelosuppression with ANC <3.0 × 109/L is salutary. Splenomegaly is an unexplained risk factor for malaria infections among children with SCA in Africa.

Sex-disaggregated analysis of acute kidney injury in hospitalized children with sickle cell anemia in Uganda.

A growing body of research is categorizing sex differences in both sickle cell anemia (SCA) and acute kidney injury (AKI); however, most of this work is being conducted in high-resource settings. Here, we evaluated risk factors and clinical parameters associated with AKI and AKI severity, stratified by sex, in a cohort of children hospitalized with SCA and vaso-occlusive pain crisis (VOC). The purpose of this study was to explore sex disparities in a high-risk, vulnerable population. This study was a secondary analysis of data collected from a cohort of Ugandan children between 2 and 18 yr of age prospectively enrolled. A total of 185 children were enrolled in the primary study; 41.6% were female and 58.4% were male, with a median age of 8.9 yr. Incident or worsening AKI (P = 0.026) occurred more frequently in female compared with male children, despite no differences in AKI on admission. Female children also had altered markers of renal function including higher creatinine levels at admission (P = 0.03), higher peak creatinine (P = 0.006), and higher urine neutrophil gelatinase-associated lipocalin (NGAL) at admission (P = 0.003) compared with male children. Female children had elevated total (P = 0.045) and conjugated bilirubin at admission (P = 0.02) compared with male children and higher rates of hematuria at admission (P = 0.004). Here, we report sex differences in AKI in children with SCA and VOC, including increased incidence and worsening of AKI in female pediatric patients, in association with an increase in biological indicators of poor renal function including creatinine, estimated glomerular filtration rate, and NGAL.NEW & NOTEWORTHY In this study, we report an increased risk of developing acute kidney injury (AKI) during hospitalization, worsening AKI, and death among females with sickle cell anemia (SCA) hospitalized with an acute pain crisis compared with males. The sex differences in AKI were not explained by socioeconomic differences, severity of pain, or disease severity among females compared with males. Together, these data suggest that female children with SCA may be at increased risk of AKI.

Screening for haemoglobin disorders: One size may not fit all.

Accurate laboratory screening for sickle cell disease and other haemoglobin disorders is expanding worldwide. Two new reports describe different methods and strategies for screening in Mali and Denmark, respectively, and their encouraging results suggest that countries should tailor their screening programmes according to local needs, resources and opportunities. Commentary on: Guindo et al. Potential for a large-scale newborn screening strategy for sickle cell disease in Mali: a comparative diagnostic performance study of two rapid diagnostic tests (SickleScan® and HemotypeSC®) on cord blood. Br J Haematol 2024;204:337-345 and Gravholt et al. The Danish national haemoglobinopathy screening programme: report from 16 years of screening in a low-prevalence, non-endemic region. Br J Haematol 2024;204:329-336.

The clinical spectrum of HbSC sickle cell disease-not a benign condition.

Sickle cell disease (SCD) includes a group of heterogenous disorders that result in significant morbidities. HbSS is the most common type of SCD and HbSC is the second most common type of SCD. The prevalence of HbSC disease in the United States and United Kingdom is ~1 in 7174 births and 1 in 6174 births respectively. Despite its frequency, however, HbSC disease has been insufficiently studied and was historically categorized as a more 'mild' form of SCD. We conducted this study of HbSC disease as part of the NHLBI funded Sickle Cell Disease Implementation Consortium (SCDIC). The SCDIC registry included 2282 individuals with SCD, ages 15-45 years of whom 502 (22%) had HbSC disease. Compared with people with sickle cell anaemia (SCA), the study found that people with HbSC disease had a higher frequency of splenomegaly (n (%) = 169 (33.7) vs. 392 (22.1)) and retinopathy (n (%) = 116 (23.1) vs. 189 (10.6)). A Many people with HbSC also had avascular necrosis (n (%) = 112 (22.3)), pulmonary embolism (n (%) = 43 (8.6)) and acute chest syndrome (n (%) = 228 (45.4)) demonstrating significant disease severity. HbSC disease is more clinically severe than was previously recognized and deserves additional evaluation and targeted treatments.

Persistent albuminuria and chronic kidney disease in adults with sickle cell anaemia: Results from a multicenter natural history study.

Clinical and laboratory correlates of chronic kidney disease (CKD) in sickle cell anaemia remain incompletely defined. In a multicenter cohort study, we evaluated the prevalence of persistent albuminuria (PA) and characteristics associated with PA, albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) using logistic, linear and multinomial regression models, respectively. Of 269 participants (median age: 30 years; 57.2% females), the prevalence of PA was 35.7%. Using baseline ACR values of <100 and ≥100 mg/g, the probabilities of PA were 30.0% and 94.6%, respectively. In multivariable logistic regression analyses, male sex (ß = 0.80 [SE = 0.36], p = 0.024) and ACE inhibitors/ARBs use (ß = 1.54 [SE = 0.43], p < 0.001) were associated with higher likelihoods of PA, while higher haemoglobin (ß = -0.33 [SE = 0.13], p = 0.009) and HbF (ß = -0.04 [SE = 0.02], p = 0.041) were associated with lower likelihoods of PA. In multivariable multinomial regression analyses, older age (ß = 0.06 [SE = 0.02], p = 0.004) and higher alkaline phosphatase (ß = 0.01 [SE = 0.00], p = 0.004) were associated with higher odds of having eGFR 60-90 versus eGFR>90 mL/min/1.73 m2 using the cystatin C-based CKD-EPI-2012 equation. Additionally, higher systolic blood pressure (ß = 0.11 [SE = 0.03], p = 0.001) and blood urea nitrogen (ß = 0.45 [SE = 0.12], p < 0.001) were associated with higher odds, while higher haemoglobin (ß = -1.22 [SE = 0.43], p = 0.004) was associated with lower odds of having eGFR<60 versus eGFR>90 mL/min/1.73 m2. PA and decreased eGFR are associated with measures of disease severity and comorbid conditions (Clinicaltrials.gov Identifier: NCT03277547).

Determinants of the haemoglobin level in patients with sickle cell disease living in sub-Saharan Africa: Major impact of the country of residence and independent effects of leucocyte and platelet counts and haemolysis.

The degree of anaemia in sickle cell disease (SCD) is a well-known contributor to morbidity and mortality. We aimed to explore the factors affecting haemoglobin (Hb) level in African SCD patients, considering haemolysis biomarkers (LDH and bilirubin level, and reticulocyte count), leucocyte and platelet counts and socio-demographic characteristics (gender, age group, country of residence and BMI). The research was part of the CADRE multinational cohort and involved 3699 SCD patients living in Mali, Senegal, Ivory Coast, Democratic Republic of Congo, Gabon and Cameroon: 2936 SS/Sß0, 587 SC and 176 Sß + patients with median Hb level of 8, 11.3 and 11.2 g/dL respectively (p < 0.001). In multivariate analysis conducted in 1394 SS/Sß0 patients, living in Cameroon, female gender, lower BMI, higher haemolysis markers (especially LDH) and higher leucocyte and platelet counts were independently associated with lower Hb level (all p < 0.05). In 497 SC and 156 Sß + patients, female gender (p < 0.001), lower BMI (p < 0.05) and higher platelet counts (p < 0.001) were independently associated with lower Hb level. Anaemia in African SCD patients is not only associated with haemolysis but also with the country of residence, lower BMI and leucocyte or platelet counts which might reflect inflammation related to infectious burden in the region.

Shift in emergency department utilization by frequent attendees with sickle cell disease during the COVID-19 pandemic: A multicentre cohort study.

While the coronavirus disease-2019 (COVID-19) might have increased acute episodes in people living with sickle cell disease (SCD), it may also have changed their reliance on emergency department (ED) services. We assessed the impact of the COVID-19 pandemic and lockdowns on ED visits in adult SCD people followed in five French reference centres, with a special focus on 'high users' (≥10 visits in 2019). We analysed the rate of ED visits from 1 January 2015 to 31 December 2021, using a self-controlled case series. Among 1530 people (17 829 ED visits), we observed a significant reduction in ED visits during and after lockdowns, but the effect vanished over time. Compared to pre-pandemic, incidence rate ratios for ED visits were 0.59 [95% CI 0.52-0.67] for the first lockdown, 0.66 [95% CI 0.58-0.75] for the second and 0.85 [95% CI 0.73-0.99] for the third. High users (4% of people but 33.7% of visits) mainly drove the reductions after the first lockdown. COVID-19 lockdowns were associated with reduced ED visits. While most people returned to their baseline utilization by April 2021, high users had a lasting decrease in ED visits. Understanding the factors driving the drop in ED utilization among high users might inform clinical practice and health policy.

Sickle cell disease in Indian tribal population: Findings of a multi-centre Indian SCD registry.

BACKGROUND: Sickle cell disease (SCD) registries provide crucial real-world data on demographics, epidemiology, healthcare, patient outcomes, and treatment efficacy. This paper presents findings from the Indian SCD Registry (ISCDR) on clinical manifestations, crisis episodes, disease management, and healthcare utilization in patients with SCD from 12 primary health centres (PHCs) in six tribal districts of India. METHODS: The ISCDR was introduced along with a three-tier screening process. Its Android-based application incorporates two electronic case report forms for patient data collection over one year. This paper presents a year's data from the ISCDR's 324 patients with SCD. RESULTS: Patients with SCD, aged one to 65 years, exhibited varied clinical manifestations. Most patients (85.2 %) were unaware of their SCD status before enrolling in ISCDR. Moderate to severe anaemia was prevalent (66.05 % and 30.56 %, respectively). Pain was a common complaint (80.86 %; CI: 76.17-85.00), while symptoms of stroke included sudden severe headaches (34.57 %; CI: 29.40-40.02). Common splenic sequestration symptoms included stomach pain (42.90 %; CI: 37.44-48.49) and abdominal tenderness (13.27 %; CI: 9.77-17.46), as a sign. Healthcare utilization was high, with 96.30 % receiving treatment and 83.64 % consuming hydroxyurea. Hospitalization occurred for 38.27 % (CI: 32.95-43.81), and 12.04 % (CI: 8.70-16.09) had blood transfusion during last year. CONCLUSIONS: ISCDR serves as a dynamic digital database on SCD epidemiology, clinical aspects, treatment and healthcare utilization. Notably, many patients lacked prior awareness of their SCD status, underscoring the need for improved awareness and care management. Integrating the registry into the national programme can streamline treatment implementation, prioritize management approaches, and optimize individual benefits.

Machine Learning Predicts Acute Kidney Injury in Hospitalized Patients with Sickle Cell Disease.

INTRODUCTION: Acute kidney injury (AKI) is common among hospitalized patients with sickle cell disease (SCD) and contributes to increased morbidity and mortality. Early identification and management of AKI is essential to preventing poor outcomes. We aimed to predict AKI earlier in patients with SCD using a machine-learning model that utilized continuous minute-by-minute physiological data. METHODS: A total of6,278 adult SCD patient encounters were admitted to inpatient units across five regional hospitals in Memphis, TN, over 3 years, from July 2017 to December 2020. From these, 1,178 patients were selected after filtering for data availability. AKI was identified in 82 (7%) patient encounters, using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria. The remaining 1,096 encounters served as controls. Features derived from five physiological data streams, heart rate, respiratory rate, and blood pressure (systolic, diastolic, and mean), captured every minute from bedside monitors were used. An XGBoost classifier was used for classification. RESULTS: Our model accurately predicted AKI up to 12 h before onset with an area under the receiver operator curve (AUROC) of 0.91 (95% CI [0.89-0.93]) and up to 48 h before AKI with an AUROC of 0.82 (95% CI [0.80-0.83]). Patients with AKI were more likely to be female (64.6%) and have history of hypertension, pulmonary hypertension, chronic kidney disease, and pneumonia than the control group. CONCLUSION: XGBoost accurately predicted AKI as early as 12 h before onset in hospitalized SCD patients and may enable the development of innovative prevention strategies.

Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

Sickle Cell Health Awareness, Perspectives, and Experiences (SHAPE) survey: Perspectives of adolescent and adult patients, caregivers, and healthcare professionals on the burden of sickle cell disease.

OBJECTIVES: Sickle cell disease (SCD) is an inherited disorder that causes lifelong complications, substantially impacting the physical and emotional well-being of patients and their caregivers. Studies investigating the effects of SCD on quality of life (QOL) are often limited to individual countries, lack SCD-specific QOL questionnaires, and exclude the caregiver experience. The SHAPE survey aimed to broaden the understanding of the global burden of SCD on patients and their caregivers and to capture the viewpoint of healthcare providers (HCPs). METHODS: A total of 919 patients, 207 caregivers, and 219 HCPs from 10, 9, and 8 countries, respectively, answered a series of closed-ended questions about their experiences with SCD. RESULTS: The symptoms most frequently reported by patients were fatigue/tiredness (84%) and pain/vaso-occlusive crises (71%). Patients' fatigue/tiredness had one of the greatest impacts on both patients' and caregivers' QOL. On average, patients and caregivers reported missing 7.5 days and 5.0 days per month, respectively, of school or work. HCPs reported a need for effective tools to treat fatigue/tiredness and a desire for more support to educate patients on long-term SCD-related health risks. CONCLUSIONS: The multifaceted challenges identified using the SHAPE survey highlight the global need to improve both patient and caregiver QOL.

Chronic kidney disease and outcomes in hospitalized sickle cell disease patients: A National Inpatient Sample analysis.

OBJECTIVES: To examine the association between chronic kidney disease (CKD) and outcomes in sickle cell disease (SCD) patients. METHODS: Patients ≥18 years with SCD in the National Inpatient Sample database between 2016 and 2018 were identified using ICD-10-CM diagnosis codes. A 1:1 propensity-score matched analysis was performed to compare in-hospital outcomes of patients with and without CKD. RESULTS: Of the 366 240 SCD admissions, 19 365 (5.3%) had CKD. The CKD group had higher odds of in-hospital mortality (odds ratio [OR] 2.59, 95% confidence interval [CI]: 1.63-4.12, p = <.01), blood transfusion (OR 1.67, 95% CI: 1.47-1.90, p < .01), mechanical ventilation (OR 2.20, 95% CI: 1.56-3.12, p = <.01), sepsis (OR 1.75, 95% CI: 1.46-2.10, p < .01), incurred higher costs ($53 255 vs. $47 294, p < .001), but had lower odds of acute chest syndrome (OR 0.71, 95% CI: 0.54-0.95, p = 0.02) and pulmonary embolism (OR 0.45, 95% CI: 0.31-0.67, p < .01). CONCLUSIONS: CKD was associated with higher mortality, higher costs, blood transfusion, sepsis, and mechanical ventilation in SCD patients. Further studies are needed to explore the reasons for the reduced odds of pulmonary embolism and acute chest syndrome.

Hydroxyurea is associated with later onset of acute splenic sequestration crisis in sickle cell disease: Lessons from the European Sickle Cell Disease Cohort-Hydroxyurea (ESCORT-HU) study.

Acute splenic sequestration crisis (ASSC) is a potentially life-threatening complication of sickle cell disease (SCD), typically occurring in young patients under 5 years of age, with a median age at first episode of less than 2 years. Because a beneficial effect of hydroxyurea (HU) on spleen perfusion and splenic function has been suspected, we hypothesized that HU treatment might be associated with later onset of ASSC in patients with SCD. To investigate this hypothesis, we analyzed data from the ESCORT-HU study on a large cohort of patients with SCD receiving HU, enrolled between January 2009 and June 2017 with a follow-up of 7309 patient-years of observation. The median age at ASSC of the 14 patients who experienced a first episode of ASSC during the study period was 8.0 [IQR: 5.0-24.1] years. The median age at HU initiation was significantly lower in these 14 patients (4.8 [IQR: 3.3-18.7] years) compared to the 1664 patients without ASSC (19.9 [8.8-33.4] years, p = .0008). These findings suggest that ASSC may occur at an unusually late age in patients receiving HU, possibly reflecting longer preservation of spleen perfusion and function secondary to early initiation of HU. Further studies are needed to better characterize the effects of HU on spleen perfusion/function and on the occurrence of ASSC in patients with SCD (ClinicalTrials.gov identifier: NCT02516579; European registry ENCEPP/SDPP/10565).

Sexually transmitted infection testing and diagnosis in adolescents and young adults with sickle cell disease.

BACKGROUND: Sexually transmitted infections (STIs) are common and disproportionately affect Black adolescents and young adults (AYAs). Less is known about STIs among Black AYAs with chronic conditions, such as sickle cell disease (AYAs-SCD). This study compared STI testing and diagnosis between AYAs-SCD and their peers, overall and among STI-related encounters. PROCEDURE: This retrospective, cross-sectional study used diagnosis and billing codes in the Pediatric Health Information System (PHIS) to identify inpatient and emergency department encounters from January 1, 2022 to May 31, 2023 among all AYAs 15-24 years and those with STI-related diagnoses (e.g., "cystitis"). STI testing and diagnosis rates were compared between AYAs-SCD, non-Black AYAs, and Black AYAs, controlling for age, sex, and encounter setting. RESULTS: We identified 3602 AYAs-SCD, 177,783 Black AYAs, and 534,495 non-Black AYAs. AYAs-SCD were less likely to be tested for STIs than non-Black AYAs (odds ratio [OR] = 0.26; adj. p < .001) and Black AYAs (OR = 0.53; adj. p < .001). When tested, AYAs-SCD were more likely to be diagnosed with an STI than non-Black AYAs (OR = 2.39; adj. p = .006) and as likely as Black AYAs (OR = 0.67; adj. p = .15). Among STI-related encounters, AYAs-SCD were less likely to be tested than non-Black AYAs (OR = 0.18; adj. p < .001) and Black AYAs (OR = 0.44; adj. p < .001). No significant differences in STI diagnoses were found in this subset between AYAs-SCD and non-Black AYAs (OR = 0.32; adj. p = .28) or Black AYAs (OR = 1.07; adj. p = .99). CONCLUSIONS: STI care gaps may disproportionately affect AYAs-SCD. STIs should be considered when evaluating symptomatic AYAs-SCD in acute settings. More research is needed to further contextualize STI care for AYAs-SCD.

Examining community-level social vulnerability and emergency department use for people living with sickle cell disease in Michigan.

This study examined associations between emergency department (ED) visits and social vulnerability index (SVI) among Michigan's population with sickle cell disease (SCD) using data from the Michigan Sickle Cell Data Collection program (n = 3658 in 2018). SVI was higher among census tracts where people with SCD resided (mean SVI = 0.67; SD = 0.27) compared to census tracts without SCD residents (mean SVI = 0.39; SD = 0.25; p < .001). For children with SCD, for every 0.1 increase in SVI score, the number of ED visits increased by 6% (IRR = 1.061; SE = 0.03; p = .038). Future research should investigate the association between SVI and ED use, at the community and household levels, to elucidate strategies to reduce ED use among children with SCD.

Emergency department 30-Day emergency department revisits among people with sickle cell disease: Variations in characteristics.

People with sickle cell disease (SCD) often have emergency department (ED) revisits. The characteristics of people with SCD with ED revisits were assessed in this study using Medicaid administrative claims data from California and Georgia, representing 2794 and 3641 individuals with SCD, respectively. In both states, those with 6+ primary care provider (PCP) encounters had the highest percentage of ED revisits. In California, those with 6+ hematology encounters had the lowest percentage of individuals with an ED revisit; in Georgia, those with 1-2 hematology encounters. Increasing access to hematologic care may reduce ED revisits among people with SCD.

Prevalence of Duffy null and its impact on hydroxyurea in young children with sickle cell disease in the United States.

Consistent with studies showing a high prevalence of the Duffy null phenotype among healthy Black Americans, this retrospective study found that Duffy null was present in >75% of a young and contemporary cohort of children with sickle cell disease (SCD) in the United States. Despite the potential for this phenotype to impact absolute neutrophil counts, hydroxyurea (HU) dosing, and outcomes, it was not associated with being prescribed a lower HU dose or having increased acute SCD visits early in the HU treatment course. Future studies are needed to confirm these findings in older children with SCD.

Description of a national, multi-center registry of patients with sickle cell disease and SARS-CoV-2 infection: Data from the Pediatric COVID-19 United States Registry.

Children with sickle cell disease (SCD) are at risk of complications from viral infections, including SARS-CoV-2. We present the clinical characteristics and outcomes of pediatric patients with SCD from the Pediatric COVID-19 United States Registry who developed acute COVID-19 due to SARS-CoV-2 infection (n = 259) or multisystem inflammatory syndrome in children (MIS-C; n = 4). Nearly half of hospitalized children with SCD and SARS-CoV-2 infection required supplemental oxygen, though children with SCD had fewer intensive care (ICU) admissions compared to the general pediatric and immunocompromised populations. All registry patients with both SCD and MIS-C required ICU admission. Children with SCD are at risk of severe disease with SARS-CoV-2 infection, highlighting the importance of vaccination in this vulnerable population.