Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial.

BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

Impact of Coronavirus-2019 On Pediatric and Adult Heart Transplantation Waitlist Activity and Mortality in The United States: A Descriptive Approach.

BACKGROUND: Transplant centers saw a substantial reduction in deceased donor solid organ transplantation since the beginning of the coronavirus 2019 (COVID-19) pandemic in the United States. There is limited data on the impact of COVID-19 on adult and pediatric heart transplant volume and variation in transplant practices. We hypothesized that heart transplant activity decreased during COVID-19 with associated increased waitlist mortality. METHODS: The United Network for Organ Sharing (UNOS) database was used to identify patients at the time of listing for heart transplant from 2017-2020. Patients were categorized as pediatric (<18 years) or adult (≥18 years) and as pre-COVID (2017-2019) or post-COVID (2020). Regional and statewide data were taken from United States Census Bureau. CovidActNow project was used to obtain COVID-19 mortality rates. FINDINGS: Among pediatric patients, average time on the waiting list decreased by 28 days. Even though the average number of pediatric transplants (n=39 per month) did not change significantly during 2020, there was a temporal decline in the first quarter of 2020 followed by a sharp increase. Overall absolute pediatric waitlist mortality decreased from 5•31 to 4•73, however female mortality increased by 2%. Regional differences in pediatric mortality were observed: Northeast, decreased by 7•5%; Midwest, decreased by 9%; West, increased by 3•5%; and South, increased by 13%. North Dakota (0•55), Oklahoma (0•21) and Hawaii (0•33) showed higher mortality than other states per 100,000. In adults, average time on waiting list increased by 40 days and there was an increase in the number of transplants from 242 to 266. Adult waitlist mortality had a larger decrease, 18•44 to 15•70, with an increase in female mortality of 7%. Regional differences in adult mortality were also observed: Northeast, decreased by 3%; Midwest, increased by 5•5%; West, increased by 4•5% and South, decreased by 5%. Iowa (0•37), Wyoming (0•22), Arkansas (0•18) and Vermont (0•19) had the highest mortality per 100,000 compared to the other states. INTERPRETATION: Pediatric heart transplant volume declined in early 2020 followed by a later increase, while adult transplant volume increased all year round. Although, overall pediatric waitlist mortality decreased, female waitlist mortality increased for both adults and pediatrics. Regional differences in waitlist mortality were observed for both pediatrics and adults. Future studies are needed to understand this initial correlation and to determine the impact of COVID-19 on heart transplant recipients. FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.