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.

A novel pilot program to reduce health inequities: A single center's experience with advocacy in pediatric gastroenterology, hepatology and nutrition

Background: Health advocacy that ?promotes social, economic, educational and political changes that ameliorate suffering and threats to human health? is an essential component of comprehensive medical care. The COVID-19 pandemic highlighted existing structural health inequities for vulnerable and marginalized populations, bringing greater visibility and urgency for providers to actively assess social determinants of health and address barriers to improve health outcomes. We aimed to create a multidisciplinary team within our pediatric gastroenterology, hepatology and nutrition division to provide comprehensive and equitable subspecialty care to all children regardless of race or ethnicity, gender identity, sexual orientation, socioeconomic status, disability, illness, language or country of origin. We organized our center's novel integrative approach to pediatric gastroenterology (GI) and hepatology-related advocacy into four action domains: 1) identify and address social disparities and health inequities;2) improve GI and hepatology programming to increase accessibility to and inclusivity for all patients;3) increase community engagement;and 4) amplify subspecialty related advocacy using innovative social media strategies. Methods: The Stanford University Division of Pediatric Gastroenterology, Hepatology and Nutrition Advocacy Group was established in January 2020 and includes 16 voluntary participants including GI trainees, attending physicians, advanced practice providers, dietitians, social workers and staff. The group relies on active cross collaboration and discussion guided by the founder of the GI advocacy group in partnership with the Associate Chair for Policy & Community Engagement as the department level sponsor. The group participates in one-hour monthly meetings with the first 30 minutes focused on ?think tank? discussions about new and ongoing GI and hepatology advocacy projects. The last 30 minutes includes invited speakers related to a current advocacy project, to provide education on community resources for the diverse patients we serve, or to hone a new skill related to pediatric subspecialty advocacy. Our group communicates between meetings through a designated email listserv and our members share a social media platform (Twitter handle @StanfordPedsGI) to promote division-wide advocacy efforts. Results: The Stanford Pediatric GI Advocacy group has worked to take action on systemic inequities and reduce and eliminate barriers to pediatric healthcare. We will share one example from each of the four action domains. To identify and address social disparities we implemented a universal outpatient social determinants of health screening, adapting the Health Leads' screening toolkit in both English and Spanish. To date we have screened approximately 1,000 patients in clinic. Members of our group helped lead a national workshop for addressing racial bias in pediatric liver transplantation (http://bit.ly/SPLITbiasworkshop), which was sponsored by the Society of Pediatric Liver Transplantation (SPLIT) and attended by leaders in transplant surgery and transplant hepatology across two one-hour sessions. To increase accessibility and inclusivity we created a Spanish language ?COVID Townhall? recording for our liver and intestinal transplant recipients (http://bit.ly/COVIDSpanishtownhall) which has been viewed over 200 times. To increase community engagement we participated in six health-related external service projects providing donations and voluntary assistance to bridge gaps and create connections in our local community. Through these efforts we have collected 30+ pounds of food, 500 children's books to establish GI and hepatology clinic libraries, 200 disposable masks, $500 for a local aquatherapy pool and $600 for aid to families in paying utility bills. Finally, to amplify the need to address these issues we established a group website (http://bit.ly/GIAdvocacy) and launched a Twitter media campaign (https://twitter.com/stanfordpedsgi). The Twitter account has produced 24 tweets with over 30,000 otal impressions, and 1,050 total engagements addressing topics related to child health advocacy in pediatric gastroenterology, hepatology, and nutrition. Conclusion: Over the course of one year, our division demonstrated the feasibility of building a team of GI and hepatology advocates, utilizing the strength of a multidisciplinary collaborative team model to successfully implement short and long-term projects. These projects varied across four domains which contributed to the overall health and wellness of our patients. Child health advocacy is a foundational component of clinical subspecialty practice to ensure equitable care for our pediatric gastroenterology and hepatology patients. Combining the clinical expertise of multiple team members of different disciplines has led to a robust effort to support the well-being and care of our patients.

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.