http://www.thelancet.com/article/S2589537022000177/pdf

Which children and young people are at higher risk of severe disease and death after hospitalisation with SARS-CoV-2 infection in children and young people: A systematic review and individual patient meta-analysis

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jth.15216

SARS-COV-2–associated coagulopathy and thromboembolism prophylaxis in children: A single-center observational study

Comorbidities are risk factors for hospitalization and serious COVID-19 illness in children and adults with sickle cell disease.

Background In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. Results The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. Conclusions Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

/pdf/initial-guidance-on-use-of-monoclonal-antibody-therapy-for-11sus5yvrj.pdf

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.

/pdf/individuals-with-sickle-cell-disease-and-sickle-cell-trait-3li9c6l1uh.pdf

Individuals with sickle cell disease and sickle cell trait demonstrate no increase in mortality or critical illness from COVID-19 - A fifteen hospital observational study in the Bronx, New York.

Faced with the rapidly evolving COVID-19 pandemic, in March 2020 the UK Government advocated strict self-isolation (‘shielding’) to protect extremely vulnerable patient groups deemed at high risk of severe SARS-CoV-2 infection. These included children and adults with sickle cell anemia (HbSS). On the advice of the National Hemoglobinopathy Panel (NHP), a multidisciplinary expert advisory group, shielding guidance was extended to all sickle cell disease (SCD) sub-types. Patients with transfusion dependent (TDT) and non-transfusion dependent thalassemia (NTDT), Diamond-Blackfan anemia (DBA) and other rare inherited anemias were also advised to shield if considered at high risk based on agreed clinical criteria. These included severe iron overload, splenectomy, diabetes and cardiac disease. Data provided by two participating centers with the largest thalassemia cohorts indicate up to 30% of patients meet these criteria. In order to evaluate the impact of these measures and inform guidance on the clinical management of COVID-19 and public health policy, a real-time survey of confirmed and suspected cases of COVID-19 in hemoglobinopathy and rare inherited anemia patients was initiated on behalf of the NHP and National Health Service (NHS) England Clinical Reference Group for Hemoglobinopathies. Data were submitted weekly by the 14 Hemoglobinopathy Coordinating Centers (HCC) in England, providing national coverage. HCC were encouraged to follow World Health Organization (WHO) case definitions which include both confirmed and clinically suspected COVID-19. Anonymised data were collected using a standardised report template (see the Online Supplementary Data) and presented weekly to the NHP. Between April 8 and May 6, 2020, a total of 195 confirmed or suspected COVID-19 cases (male: 87; female: 108) were reported. The timeline of case accrual is shown in Figure 1A. The median age was 33 years (range: 6 weeks to 92 years). The distribution according to age and sex is shown in Figure 1B. PCR for SARS-CoV-2 RNA was positive in 99 of 157 (63%) cases tested (Figure 2A). Laboratory confirmation was not available for 34 (17.4%) cases, 31 of which were managed in the community for suspected COVID-19 before widespread testing became available. SCD accounted for 166 (85.1%) of cases reported, with 129 (77.7%) severe (HbSS or HbSβ-thalassemia) and 37 (22.3%) mild (HbSC, HbSβ-thalassemia or HbSE) genotypes (Figures 2A-B). There were 149 adults and 17 children (defined as ≤18 years). Ninety-five (57%) were female. One hundred and twenty-eight (77.1%) SCD patients were admitted to hospital of whom 15 (11.7%), all adults, required non-invasive and/or mechanical ventilation (Figure 2B). The proportion of patients who required critical care was higher in mild genotypes, 8 of 29 (27.6%), than severe genotypes, 7 of 99 (7.1%) (Figure 2B). Sixty of 154 (39%) patients for whom data were available received transfusion (red cell exchange 46 [29%]; simple [top-up] transfusion 15 [10%]) during the COVID-19 episode. The proportion of transfused patients was similar for children and adults. Outcome was analyzed for cases with a completed COVID-19 course (n=142), excluding those with a continuing inpatient stay or missing data. Of patients with a completed course, 131 (92.2%) have recovered and 11 (8.4%) died. The median age of patients who died was higher (51 years, range: 19-68 years) than those who recovered (31 years, range: 6 weeks to 72 years, P=0.0042). No deaths occurred in children. Among adult patients admitted to hospital mortality was 9.2 % (10 of 109). One patient died outside hospital, in a community residential care facility. In six patients who died, comorbid conditions (stroke: 1, cardiopulmonary disease: 2; cancer: 1; chronic kidney disease (stage G5): 1; hypertension: 1) associated with increased risk of death in COVID-19 were present. Seven of 10 patients who required mechanical ventilation died. As of May 6, 2020, 19 patients were receiving inpatient treatment, including non-invasive ventilation in one case. Data were missing for five patients managed outside hospital. The association of patient variables with survival status was analyzed in SCD patients (n=77) with a laboratory confirmed COVID-19 diagnosis who were admitted to hospital (Table 1). The overall mortality in the group was 10.4%. In contrast to the association of older age and male sex with risk of COVID-19 related death in other populations, no significant correlation was found with age, sex or SCD genotype. Mortality was higher in females and mild genotypes though the differences did not reach significance. As of May 6, 2020, 206,715 cases of COVID-19 with 30,615 (14.8%) deaths had been reported in the UK. At first sight this suggests SCD patients are not more vulnerable to COVID-19. The age demographic profile of COVID-19 however differs markedly in the SCD and general population. In the ISARIC study of 20,133 cases of confirmed COVID-19 admitted to hospitals in the UK between February 6 and April 19, 2020, the median age was 73 years compared with a median age of 31 years in our cohort. We therefore compared the age adjusted risk of COVID-19 related death in SCD with that of the general population combining contemporaneous data from our survey, the National Hemoglobinopathy Registry (NHR) and OpenSAFELY study. The latter (data cut May 6) quantified risk factors for COVID-19 related death in England by linking primary care electronic health records of 17 million patients with data from the COVID-19 National

/pdf/real-time-national-survey-of-covid-19-in-hemoglobinopathy-4tkfnqmyot.pdf

Real-time national survey of COVID-19 in hemoglobinopathy and rare inherited anemia patients.

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Real-time national survey of COVID-19 in hemoglobinopathy and rare inherited anemia patients.