The evolution of the COVID-19 pandemic in paediatric patients with sickle cell disease: From Alpha to Omicron.

We compare the impact of SARS-CoV-2 variants on healthcare utilization and clinical presentation in paediatric patients with sickle cell disease (SCD). One hundred and ninety-one unique patients with SCD and positive SARS-CoV-2 polymerase chain reactions were identified between March 2020 and January 2022. Hospitalizations, which accounted for 42% (N = 81) of cases, were highest during the Delta dominant era (48%) and lowest during Omicron (36%) (p = 0.285). The most common SCD-related complication was vaso-occlusive pain (37%, N = 71), which accounted for 51% of all hospital admissions (N = 41), and acute chest was highest in the Alpha variant era (N = 15). Overall, COVID-19 remained mild in clinical severity within most paediatric SCD patients.

Examining the Association Between MIS-C and the Child Opportunity Index at a Single Center.

OBJECTIVE: To describe associations between the Child Opportunity Index (COI) and multisystem inflammatory syndrome of childhood (MIS-C) diagnosis among hospitalized children. METHODS: We used a retrospective case control study design to examine children ≤21 years hospitalized at a single, tertiary care children's hospital between March 2020 and June 2021. Our study population included children diagnosed with MIS-C (n = 111) and a control group of children hospitalized for MIS-C evaluation who had an alternative diagnosis (n = 61). Census tract COI was the exposure variable, determined using the patient's home address mapped to the census tract. Our outcome measure was MIS-C diagnosis. Odds ratios measured associations between COI and MIS-C diagnosis. RESULTS: Our study population included 111 children diagnosed with MIS-C and 61 children evaluated but ruled out for MIS-C. The distribution of census tract overall COI differed significantly between children diagnosed with MIS-C compared with children with an alternate diagnosis (P = .03). Children residing in census tracts with very low to low overall COI (2.82, 95% confidence interval [CI]: 1.29-6.17) and very low to low health/environment COI (4.69, 95% CI 2.21-9.97) had significantly higher odds of being diagnosed with MIS-C compared with children living in moderate and high to very high COI census tracts, respectively. CONCLUSION: Census tract child opportunity is associated with MIS-C diagnosis among hospitalized children suggesting an important contribution of place-based determinants in the development of MIS-C.

Clinical outcomes of children and adolescents with sickle cell disease and COVID-19 infection: A year in review at a metropolitan tertiary pediatric hospital

Background COVID-19 was declared a global pandemic in March 2020. Early reports were primarily in adults, and sickle cell disease (SCD) was classified as a risk factor for severe COVID-19 disease. However, there are a limited number of primarily multi-center studies reporting on the clinical course of pediatric patients with SCD and COVID-19. Methods We conducted an observational study of all patients with SCD diagnosed with COVID-19 at our institution between March 31, 2020, and February 12, 2021. Demographic and clinical characteristics of this group were collected by retrospective chart review. Results A total of 55 patients were studied, including 38 children and 17 adolescents. Demographics, acute COVID-19 clinical presentation, respiratory support, laboratory findings, healthcare utilization, and SCD modifying therapies were comparable between the children and adolescents. Seventy-three percent (N = 40) of all patients required emergency department care or hospitalization. While 47% (N = 26) were hospitalized, only 5% (N = 3) of all patients required intensive care unit admission. Patients frequently had concurrent vaso-occlusive pain crisis (VOC) (N = 17, 43%) and acute chest syndrome (ACS) (N = 14, 35%). Those with ACS or an oxygen requirement had significantly higher white blood cell count, lower nadir hemoglobin, and higher D-dimers, supporting a pro-inflammatory and coagulopathic picture. Non-hospitalized patients were more likely to be on hydroxyurea than hospitalized patients (79 vs. 50%, p = 0.023). Conclusion Children and adolescent patients with SCD and acute COVID-19 often present with ACS and VOC pain requiring hospital-level care. Hydroxyurea treatment appears to be protective. We observed no mortality despite variable morbidity.

Clinical outcomes of children and adolescents with sickle cell disease and COVID-19 infection: A year in review at a metropolitan tertiary pediatric hospital.

Background: COVID-19 was declared a global pandemic in March 2020. Early reports were primarily in adults, and sickle cell disease (SCD) was classified as a risk factor for severe COVID-19 disease. However, there are a limited number of primarily multi-center studies reporting on the clinical course of pediatric patients with SCD and COVID-19. Methods: We conducted an observational study of all patients with SCD diagnosed with COVID-19 at our institution between March 31, 2020, and February 12, 2021. Demographic and clinical characteristics of this group were collected by retrospective chart review. Results: A total of 55 patients were studied, including 38 children and 17 adolescents. Demographics, acute COVID-19 clinical presentation, respiratory support, laboratory findings, healthcare utilization, and SCD modifying therapies were comparable between the children and adolescents. Seventy-three percent (N = 40) of all patients required emergency department care or hospitalization. While 47% (N = 26) were hospitalized, only 5% (N = 3) of all patients required intensive care unit admission. Patients frequently had concurrent vaso-occlusive pain crisis (VOC) (N = 17, 43%) and acute chest syndrome (ACS) (N = 14, 35%). Those with ACS or an oxygen requirement had significantly higher white blood cell count, lower nadir hemoglobin, and higher D-dimers, supporting a pro-inflammatory and coagulopathic picture. Non-hospitalized patients were more likely to be on hydroxyurea than hospitalized patients (79 vs. 50%, p = 0.023). Conclusion: Children and adolescent patients with SCD and acute COVID-19 often present with ACS and VOC pain requiring hospital-level care. Hydroxyurea treatment appears to be protective. We observed no mortality despite variable morbidity.

Pediatric Sickle Cell Disease and the COVID-19 Pandemic: A Year in Review at Children's National Hospital

Background: Over the past year, COVID-19 was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in over 100 million cases and >3 million deaths worldwide according to the World Health Organization (WHO). Morbidity and mortality have been highest in adults, particularly in those with underlying conditions including hypertension, diabetes, and obesity. Children, thus far, have largely remained either asymptomatic or presented with mild symptoms. However, sickle cell disease (SCD) was classified as a risk factor for severe COVID-19 disease in both adults and pediatric patients. Objective: To describe the one-year experience of the clinical course, management, and treatment of COVID-19 in children, and young adults with SCD at Children's National Hospital (CNH). Methods: This was a single-center, observational cohort study of 55 children (age <18 years) and young adult (age ≥ 18 years) patients with SCD and PCR confirmed SARS-CoV-2 infection at CNH between March 31, 2020, and February 12, 2021 (Figure 1A). Results: Sixty-nine percent were children (N=38) and 31% were young adults (N=17). The mean age was 11.6 years with 51% females (N=28) and 49% males (N=27). Seventy-five percent of cases were Hgb SS, 15% Hgb SC, and 11% Hgb SBeta Thalassemia Zero (Table 1). Fever (45%) was the most common presenting symptom;only 9% had a loss of taste or smell (Figure 1B). Twenty-two percent were asymptomatic at presentation. Among the 40 patients who presented to the emergency department (ED) or were hospitalized, 50% (N=20) presented with vaso-occlusive pain crisis (VOC), 42% with Acute Chest Syndrome (ACS), 2% with splenic sequestration, and 2% with Venous Thromboembolism. Only 3% were admitted to the ICU (N=2 young adults, N=1 children);none of whom were on hydroxyurea. There were no differences in hospitalization rates between Hgb SS and Hgb SC patients (Table 1). Lower oxygen saturation (02 Sat)(02 Sat <95%: 62% vs 16% p=0.004), fevers (69% vs 16%, p=0.001), VOC pain crisis (50% vs 24%, p=0.047), and ACS (65% vs 3%, p<0.001) were more common in hospitalized patients vs. non-hospitalized patients. Patients with ACS experienced a longer length of stay (6 days vs. 3 days p=0.008), lower oxygen saturation (02Sat<95%: 81% vs 13% p<0.001), higher white blood cell count (13.3 vs 9.0 K/mcL, p=0.009), lower hemoglobin nadir (6.8 vs. 9.6 gm/dL, p= 0.049), and elevated D-dimers (4.1 vs. 0.8 ug/mL, p=0.002) compared to those without ACS. The types of treatment received by patients requiring hospitalization or ED visits included ceftriaxone (N=28, 70%), azithromycin (N=15, 37.5%), remdesivir (N=6,15%) convalescent plasma(N=1,2.5%). Blood transfusion was required in 29% of the 55 SCD COVID-19 cases (N=16) and 76% (N=13) of the ACS patients. Twenty-six percent (N=17) of hospitalized patients were anticoagulated with either enoxaparin or rivaroxaban according to CNH's COVID-19 anticoagulation treatment protocol. There were similar rates of healthcare utilization, SCD modifying therapies, acute COVID-19 clinical presentation, respiratory support, and laboratory findings (hematologic, inflammatory) between the children and young adults. However, young adults were more likely to be on crizanlizumab treatment (18% vs 0%, p=0.026) and have an elevated D-Dimer (4.0 vs 1.0, p=0.012) on laboratory evaluation. Conclusion: Our case series reveals that the demographics and clinical presentation between our SCD children and young adult patients with COVID-19 were similar overall. While the morbidity was high, there was no mortality. Those that were hospitalized had lower oxygen saturation levels, higher incidences of fever, and higher morbidity presenting with VOC and ACS. Patients with ACS and/or an oxygen requirement had significantly higher WBC count, lower nadir hemoglobin, and higher D-dimers in a small subset of patients supporting a pro-inflammatory and coagulopathic picture. Our study will add to a growing body of literature on SCD COVID-19 cases. Figure 1 Disclosures Darbari:†Global Blood Therapeutics: Consultancy;Hilton Publishing Inc.: Consultancy;Novartis: Consultancy. Majumdar:  Asklepion Pharma: Consultancy, Patents & Royalties: IV L-Citrulline in the use of sickle cell pain crisis. Campbell:  Novartis Pharmaceuticals Corporation: Consultancy, Research Funding.

Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.