Updates From the NASPGHAN/SPLIT SARS-CoV2 International Registry.

Abstract

Reply: We acknowledge the authors of “SARS-CoV-2 in pediatric liver transplant recipients: the European experience” response to our article reporting the NASPGHAN/SPLIT SARS-CoV2 registry experience (1). In contrast, they note that liver transplant (LT) recipients had higher rates of hospitalization, including intensive care unit (ICU) admission, than patients with chronic liver disease (LD). The NASPGHAN/SPLIT SARS-CoV2 international registry has increased to 180 LT recipients and 76 patients with LD (Table 1). In this expanded cohort, LT recipients were still less likely to require hospitalization (odds ratio [OR] = 0.32, 95% confidence interval [CI]: 0.17–0.59, P < 0.0001) or ICU level care (OR = 0.05, 95% CI: 0.010.17, P < 0.001) compared with LD patients. No LT recipients required mechanical ventilation or died of SARS-CoV2. Nine patients with LD required mechanical ventilation, and three patients with LD died. Differences between registry outcomes may be partially explained by the higher proportion of patients with obesity and NAFLD with LD in our cohort. Obesity is associated with worse outcomes in children with SARS-CoV2 infection (1,2–5). Buescher et al additionally suggest a role of combined immunosuppression leading to increased hospitalization in LT recipients. In our larger LT cohort, the degree of immunosuppression was not associated with higher odds of hospitalization (OR = 1.6, 95% CI: 0.69–3.8, P = 0.20). TABLE 1 - Baseline characteristics and clinical data for patients with disease of the native liver and liver transplant recipients with positive test for the severe acute respiratory syndrome coronavirus 2 Disease of the native liver (N = 76) Liver transplant recipient (N = 180) P value Baseline characteristics Age (y), median (IQR) 9.5 (4–16) 11.5 (5–17) 0.05 Male gender (%) 45 (59) 93 (52) 0.2 Primary liver condition (%) <0.001 NAFLD 13 (17) 0 Biliary atresia 18 (24) 85 (47) Acute liver failure 4 (5) 16 (9) Autoimmune hepatitis 13 (17) 7 (4) Metabolic 6 (8) 23 (13) Malignancy 3 (4) 18 (10) Other cholestatic liver disease 15 (20) 21 (12) Other 4 (5) 10 (6) Comorbid conditions (%) None 20 (26) 97 (54) Overweight/obesity 18 (24) 13 (7) <0.001 Cardiac 10 (13) 22 (12) 0.8 Gastrointestinal 11 (14) 10 (6) 0.03 Pulmonary 6 (8) 11 (6) 0.6 Renal 2 (3) 16 (9) 0.07 Endocrine 4 (5) 5 (3) 0.4 Other autoimmune conditions 2 (3) 5 (3) Time since LT (y), median (IQR) – 4.5 (2–11) Clinical data Presenting symptoms (%) Fever 27 (36) 49 (27) Respiratory symptoms 36 (47) 65 (36) Constitutional symptoms 11 (14) 23 (13) Gastrointestinal symptoms 18 (24) 29 (16) Asymptomatic 16 (21) 63 (35) Highest level of care (%) Outpatient 28 (37) 147 (82) <0.001 Hospital floor 29 (38) 30 (16) <0.001 ICU 19 (25) 3 (12) <0.001 Highest respiratory support (%) <0.001 None 60 (79) 177 (98) Nasal cannula/CPAP/BiPAP 7 (9) 3 (2) Mechanical ventilation 6 (8) 0 High frequency oscillatory ventilation 3 (4) 0 Final clinical outcome (%) 0.02 Death 3 (4) 0 Recovery 67 (88) 175 (97) Still active in clinical course/pending 7 (8) 5 (3) ICU = intensive care unit; IQR = interquartile range; LT = liver transplant; N = number; NAFLD = non-alcoholic fatty liver disease. We agree with Buescher et al regarding the utility of collaborative registry studies to inform the care of pediatric LT recipients and children with LD. Our registry continues to collect data (https://bit.ly/NASPGHAN_SPLIT_COVIDregistry). Ongoing submissions remain critical as we continue to explore variants, breakthrough infections, and antibody response to SARS-CoV2 vaccination in pediatric solid organ transplant recipients (6,7).