Results
This cohort of 27 children and young adults hospitalized with symptomatic COVID-19 (Table 1) was roughly equal by gender, with 14 (52%) males and 13 (48%) females. The numbers of patients in different age ranges were 3 (11%) less than 1 year, 4 (15%) 1 through 6 years, 8 (30%) 7 through 12 years, and 12 (44%) 13 through 21 years (Table 1). The background racial and ethnic makeup of the Bronx, New York based on the 2019 census report is approximately 44% Black and 45% White, with 56% of all races identifying as Hispanic or Latino ethnicity. In this cohort 3 (11%) patients self-identified as Black, 1 (4%) White, 11 (41%) other, and 16 (59%) patients self-identified as Spanish/Hispanic/Latino.  Obesity and sickle cell disease were the most prevalent comorbid conditions, with 5 (19%) patients having BMI > 95th percentile, and 5 (19%) having sickle cell anemia.
 
 Clinically, 16 (59%) patients in this cohort had severe or critical illness due to COVID-19, based on established criteria (grades asymptomatic, mild, moderate, severe, critical) 6,  and corresponding to grades 5 and higher by the WHO progression scale (grades 1-10),11 and 14 (52%) patients required increased ventilatory support. This was defined by the need for > 5L oxygen via nasal cannula, high-flow nasal cannula, non-rebreather mask, or intubation. These patients were labelled as the “High Ventilatory Support” sub-group. Patients not requiring any ventilatory support or only oxygen supplementation of < 5L oxygen via nasal cannula were labeled as the “Low Ventilatory Support” sub-group. 9 (33%) patients required intubation. Four (15%) patients died of COVID-19 complications.
 
Coagulation parameters were abnormal in much of the cohort (Table 1). Only one (5%) of the 22 patients whose D-dimer was measured had a D-Dimer < 0.5 ug/mL (institutional normal range 0.27-0.50 ug/mL) and the mean peak D-dimer value was 6.41 ug/mL (range 0.27 – 16.9 ug/mL). PT and PTT were prolonged with mean peak values of 17.8 seconds (range 13.8-43.3 seconds) and 65.6 seconds (range 29.3 – 200 seconds), respectively (ULN 14.8 seconds and 44.8 seconds, respectively). Platelet counts were primarily in the normal or high range, with mean peak count of 416 k/uL (range 183 – 789 k/uL). There were 11 (41%) patients with platelets < 150 k/uL (institutional lower limit of normal), and the mean platelet nadir of the cohort was 175 k/uL (range 5 – 683 k/uL). Seven (26%) patients were significantly thrombocytopenic (< 50 k/uL). Fibrinogen was elevated with mean peak value of 642 mg/dL (range 227 – 1800 mg/dL, ULN 283 mg/dL). All lab testing was performed in the hospital laboratory with the usual quality assurance measures in place.
 
Venous thromboembolism (VTE) was identified in 7 (26%) patients (Table 2). Three (11%) patients developed DVT and 4(15%) developed PE. One of these patients had bilateral PE.  A requirement for increased ventilatory support was a risk factor for VTE, with 7 of 14 (50%) patients in the High Ventilatory Support group developing VTE as compared to none of 13 patients in the Low Ventilatory Support group (p=0.006) (Table 3). Elevated D-dimer was not a statistically significant risk factor for VTE in the cohort, potentially due to small sample size. However, there was a trend of D-dimer > 5 ng/uL in patients with VTE, with 2 of 11 (18%) and 5 of 11 (45%) patients developing VTE with D-dimer < 5 and > 5 ug/mL, respectively. Obesity was not associated with VTE in our cohort, potentially due to inadequate statistical power from a small sample size. All three patients with DVT and 2 of 4 (50%) patients with PE (total 5 of 7, 71%) had central venous lines, and 11 of 20 (59%) without VTE had central venous lines. This difference too did not reach statistical significance (p = .446), perhaps due to small sample size. Given our relatively small sample size and the correlated nature of these variables, the independent contribution of each risk factor to VTE could not be statistically analyzed by regression modeling.  
 
Children and young adults with symptomatic COVID-19 were at risk for VTE despite prophylactic anticoagulation, as 4 (57%) of the 7 patients with confirmed VTE were on prophylaxis. Eleven (41%) patients received prophylactic anticoagulation, with 10 (91%) of those patients receiving low molecular weight heparin (LMWH, enoxaparin) and 1 (9%) 20 year old patient receiving apixaban. The LMWH was dosed at 0.75 mg/kg BID for neonates up to 2 months, and 0.5 mg/kg BID for over 2 months, with titration of anti-Xa level to 0.2 – 0.4 ng/mL (Based on CHEST guidelines12 and institutional anticoagulation guidelines).
 
Six (60%) of the 10 patients receiving LMWH had their dose titrated to ant-Xa level, and none of these patients developed VTE. Four patients received fixed dose LMWH, which was either 40 mg per day (standard adult prophylactic dose) or fixed dosing based on weight (generally for obese patients13). Three (75%) of the 4 patients receiving fixed-dose prophylactic LMWH developed VTE, of these individuals one was obese. The remaining patient on prophylaxis was on apixaban, 2.5 mg twice daily, and developed a PE. Although the numbers are small, we did not see breakthrough VTE on anti-Xa-monitored prophylactic dosing of LMWH. No clear pattern was identified in the subset that developed VTEs on prophylactic anticoagulation, except the for the anticoagulation choice/regimen. The remaining 3 confirmed VTEs occurred in patients on therapeutic dosing of anticoagulation. Since therapeutic anticoagulation was often initiated in the most ill patients, comparison of VTE rates to the patients on prophylaxis is not feasible. It should be noted that all patients in this cohort were started on guideline based anticoagulation upon admission. Thus, unless their VTE developed before admission, these patients all received anticoagulation before VTE diagnosis and delayed start of anticoagulation was not identified as the cause for breakthrough VTE. Overall, the anticoagulation was well tolerated and no cases of grade 4 or higher bleeding were observed. Two patients had oozing from indwelling central venous line insertion sites and one of those had hematuria but neither had life-threatening hemorrhage.