Antibody Response to 3-Dose SARS-CoV-2 mRNA Vaccination in Pediatric Solid Organ Transplant Recipients

Purpose: We report the immunogenicity and safety of a third BNT162b2 vaccine in pediatric solid organ transplant recipients (pSOTRs). Method(s): Samples from pSOTRs (12-18 years) enrolled in our multicenter, observational study (COVID-19 Antibody Testing of Recipients of Solid Organ Transplants and Patients with Chronic Diseases) who received a third vaccine (V3) were analyzed for antibodies to SARS-CoV-2 spike protein receptor-binding domain, with a positive cutoff of >=0.8 and maximum titer of >2500 U/mL. Pre-V3 samples were 1-3 months after vaccine 2, and post-V3 were 1 month after vaccine 3. Result(s): Thirty-seven pSOTRs (46% heart, 24% liver, 27% kidney, 3% multi) received V3. Median (interquartile range [IQR]) age was 15 (14-16) years;42% were male and 78% white. pSOTRs were median (IQR) 9 (6-13) years from transplant. Four (11%) patients had prior SARS-CoV-2 infection. Antibody titers were positive in 26/37 (70%) patients pre-V3 and 32/37 (86%) post-V3 (Figure). Median (IQR) antibody titers were higher post-V3 (2500 [1581-2500] U/mL) than pre-V3 (211 [0.8-2500] U/mL) in paired analysis (p<0.001). 6/11 (55%) pSOTRs with negative pre-V3 titers seroconverted, with a post-V3 median (IQR) titer of 418 (132-1581) U/ mL. Transplant within 3 years was associated with negative post-V3 titer (p=0.037). Main side effects after V3 were pain (71%) and fatigue (50%). No patients reported allergic reaction, myocarditis, or rejection. One patient tested positive for SARSCoV- 2 between vaccines 2 and 3, with negative pre- and post-V3 titers. At time of first vaccine, this patient was transplanted a year ago, treated for rejection recently, and taking 3 immunosuppression agents including an antimetabolite. Conclusion(s): In this limited cohort, 86% of pSOTRs had a positive antibody response after three SARS-CoV-2 vaccines with no adverse events. Importantly, 55% of pSOTRs with prior negative response seroconverted post-V3, and 100% of pSOTRs with positive response increased their antibody titer or remained at maximum titer. Our preliminary results suggest the benefit of a third vaccine for adolescent pSOTRs based on antibody response;larger studies are needed to assess vaccine effectiveness.

OPTN/SRTR 2020 Annual Data Report: Liver.

This year was marked by the COVID-19 pandemic, which altered transplant program activity and affected waitlist and transplant outcomes. Still, 8906 liver transplants were performed, an all-time high, across 142 centers in the United States, and pretransplant as well as graft and patient survival metrics, continued to improve. Living donation activity decreased after several years of growth. As of June 30, 2020, 98989 liver transplant recipients were alive with a functioning graft, and in the context of increasing liver transplant volume, the size of both the adult and pediatric liver transplant waitlists have decreased. On February 4, 2020, shortly before the pandemic began, a new liver distribution policy based on acuity circles was implemented, replacing donor service area- and region-based boundaries. A policy change to direct pediatric livers to pediatric recipients led to an increase in deceased donor transplant rates and a decrease in pretransplant mortality rate among children, although the absolute number of pediatric transplants did not increase in 2020. Among adults, alcohol-associated liver disease became the predominant indication for liver transplant in 2020. After implementation of the National Liver Review Board and lower waitlist priority for most exception cases in 2019, fewer liver transplants were being performed via exception points, and the transplant rate between those with and without hepatocellular carcinoma has equalized. Women continue to experience higher pretransplant mortality and lower rates of liver transplant than men.

The impact of sars-cov2 infection in children with liver disease: An international observational registry study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) on children with underlying liver disease (LD) is unknown. We aim to report outcomes for pediatric patients with LD from the joint North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the Society of Pediatric Liver Transplantation (SPLIT) SARS-CoV2 registry Methods: We collected data from patients younger than 21 years with LD from 6 countries and laboratory-confirmed SARS-CoV2 infection reported to a multicenter observational cohort study between April 2020 and May 2021. Results: Seventy-three (59% male,55% white, 23% Hispanic) children with a median age of 9 years were reported in the registry. The most common causes of LD were biliary atresia (22%) followed by autoimmune hepatitis (16%) and non-alcoholic fatty liver disease (16%). Five patients (7%) presented in acute liver failure (ALF);all recovered without the need for a liver transplant. Four patients presented with multisystem inflammatory syndrome in children (2 with ALF, 2 without ALF) with one death reported. The most common presenting symptoms were constitutional (49%) including fever and fatigue followed by respiratory symptoms (47%). Twenty two percent (n=16) of patients were asymptomatic at the time of diagnosis. Twentythree percent had radiologic evidence of pneumonia and 14% reported co-infections. Median peak INR was 1.4, peak total bilirubin 2.9 (mg/dl), peak ALT 129 (IU/l) and nadir albumin 3.1 (g/dl). Sixty-four percent of patients required hospitalization;40% (n=19) in the ICU and 60% (n=28) non-ICU for a median of 6 and 7 days, respectively. Twenty-two percent of patients required respiratory support including mechanical ventilation (n=6), high-frequency oscillatory ventilation (n=3), highflow nasal cannula (n=5) and regular nasal cannula (n=2) for a median of 6 days. Nine patients required vasoactive agents, 3 required renal replacement therapy and 2 patients required ECMO. Sixty-six percent did not receive any SARSCoV2 directed treatment. Twelve (16%) patients developed new liver-related complications including ascites (n=9), GI bleeding (n=2), encephalopathy (n=3), progression of endstage liver disease (n=2) and infection (n=1). There were a total of 3 (4.1%) deaths (20yr, 17yr and 6month of age at time of death) reported secondary to acute on chronic liver failure with respiratory failure and multiorgan failure Conclusion: Contrary to healthy children, almost 2/3rd pediatric patients with LD testing positive for SARS-CoV2 required hospitalization with death reported in 4% of cases. Acute liver failure is rare with SARS-CoV2 infection with recovery reported without the need for liver transplantation. Close monitoring is needed due to an increased risk of underlying liver disease complications and death, particularly in children with end-stage liver disease awaiting transplantation.