Pediatric Solid Organ Transplant Population Research Articles

1096. Riding the Waves: Infection by SARS-CoV-2 Variants in Solid Organ Transplant Recipients at Texas Children’s Hospital

Abstract Background Texas Children’s Hospital is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exist about SARS-CoV-2 infection (COVID-19) in the pediatric SOT population. We evaluated the impact of different SARS-CoV-2 variants in a cohort of PCR positive SOT recipients. Methods SOT recipients with a positive SARS-CoV-2 PCR test from 3/1/2020 to 2/28/2022 were included in the cohort. The study period was divided into 3 eras based on the predominant circulating variant of SARS-CoV-2: 3/20-6/21 original strain/Alpha, 7/21-11/21 Delta, and 12/21-2/22 Omicron variants. Retrospective medical record review was performed; Chi-squared and Fischer exact test were used to compare groups. Results A total of 269 of 1031 (26%) SOT recipients tested positive for SARS-CoV-2 during the study period. By organ, 87/335 (26%) heart, 57/224 (25%) kidney, 92/405 (23%) liver, and 25/67 (37%) lung recipients had COVID-19 infection. By era, there were 99 (37%) original strain/ Alpha, 65 (24%) Delta, and 105 (39%) Omicron. The patients’ median age was 12.72 years (IQR 6.6, 15.1) with a minority of recipients being female (42%). Common comorbidities included hypertension (50%), obesity (13%), diabetes (10%), and chronic kidney disease (10%); 34% had no comorbidities aside from chronic immunosuppression post-transplant. Overall, 80% of recipients were symptomatic (Figure 1), and 50 (19%) required hospitalization. Hospitalization rates were highest (29%) during Delta, compared with 18% for original/Alpha and 13% for Omicron (p=0.02) eras. Need for respiratory support, ICU admission, and all-cause mortality did not vary by era (Table 1). Three SOT recipients (2 original/Alpha and 1 Delta) were diagnosed with multi-inflammatory syndrome in children (MIS-C). Conclusion Our study suggests that pediatric SOT recipients have a high risk for hospitalization and short-term complications with COVID-19; Omicron appears to cause less severe disease, including MIS-C. Additional studies are needed to understand long-term complications of COVID-19 in SOT recipients. Disclosures Elizabeth A. Moulton, MD, PhD, Pfizer: Grant/Research Support Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB.

The impact of COVID-19 on the pediatric solid organ transplant population

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted all aspects of healthcare including solid organ transplantation. In this review, we discuss the specific impact of COVID-19 on the pediatric solid organ transplant population including access to grafts for pediatric transplant candidates as well as COVID-19 disease manifestations in pediatric transplant recipients. We address the current knowledge of prevention and management of COVID-19 in pediatric transplant recipients and provide additional information regarding social distancing, infection prevention and return to school.

A Smartphone App to Increase Immunizations in the Pediatric Solid Organ Transplant Population: Development and Initial Usability Study

BackgroundVaccine-preventable infections result in significant morbidity, mortality, and costs in pediatric transplant recipients. However, at the time of transplant, less than 20% of children are up-to-date for age-appropriate immunizations that could prevent these diseases. Smartphone apps have the potential to increase immunization rates through their ability to provide vaccine education, send vaccine reminders, and facilitate communication between parents and a multidisciplinary medical group.ObjectiveThe aim of this study was to describe the development of a smartphone app, Immunize PediatricTransplant, to promote pretransplant immunization and to report on app functionality and usability when applied to the target population.MethodsWe used a mixed methods study design guided by the Mobile Health Agile Development and Evaluation Lifecycle. We first completed a formative research including semistructured interviews with transplant stakeholders (12 primary care physicians, 40 parents or guardians of transplant recipients, 11 transplant nurse coordinators, and 19 transplant subspecialists) to explore the acceptability of an immunization app to be used in the pretransplant period. Based on these findings, CANImmunize Inc developed the Immunize PediatricTransplant app. We next held 2 focus group discussions with 5-6 transplant stakeholders/group (n=11; 5 parents of transplant recipients, 2 primary care physicians, 2 transplant nurse coordinators, and 2 transplant subspecialists) to receive feedback on the app. After the app modifications were made, alpha testing was conducted on the functional prototype. We then implemented beta testing with 12 stakeholders (6 parents of transplant recipients, 2 primary care doctors, 2 transplant nurse coordinators, and 2 transplant subspecialists) to refine the app through an iterative process. Finally, the stakeholders completed the user version of the Mobile Application Rating Scale (uMARS) to assess the functionality and quality of the app.ResultsA new Android- and Apple-compatible app, Immunize PediatricTransplant, was developed to improve immunization delivery in the pretransplant period. The app contains information about vaccine use in the pretransplant period, houses a complete immunization record for each child, includes a communication tool for parents and care providers, and sends automated reminders to parents and care providers when immunizations are due. During usability testing, the stakeholders were able to enter a mock vaccine record containing 16 vaccines in an average of 8.1 minutes (SD 1.8) with 87% accuracy. The stakeholders rated engagement, functionality, aesthetics, and information quality of the app as 4.2/5, 4.5/5, 4.6/5, and 4.8/5, respectively. All participants reported that they would recommend this app to families and care teams with a child awaiting solid organ transplant.ConclusionsThrough a systematic, user-centered, agile, iterative approach, the Immunize PediatricTransplant app was developed to improve immunization delivery in the pretransplant period. The app tested well with end users. Further testing and agile development among patients awaiting transplant are needed to understand real-world acceptability and effectiveness in improving immunization rates in children awaiting transplant.

Self-reported physical activity and lack of association with health-related quality of life in a pediatric solid-organ transplant population.

Physical activity (PA) has been shown to have benefits, including improving health-related quality of life (HRQOL). However, there are few and conflicting studies assessing PA and its relationship with HRQOL in a pediatric solid-organ transplant (SOT) population. The aim of this study was to assess whether overall HRQOL was associated with PA and to determine whether that association was independent of other baseline and contemporaneous clinical and demographic indicators. A retrospective cross-sectional review was performed on 55 pediatric transplant patients (13heart, 27kidney, and 15liver transplant). PA was measured by PAQ-C/PAQ-A, and HRQOL was measured using PedsQL. Demographics, baseline, and contemporaneous data were collected. There were no significant differences in baseline and contemporaneous characteristics between heart, kidney, and liver transplant recipients. SOT recipients were 15.0 (11.0-18.0) years old at completion of surveys. Median PAQ score was 2.3 (1.6-3.2), PedsQL total score was 77 (65-91), and PedsQL physical functioning score was 88 (72-97). The PedsQL total score was not significantly associated with PAQ score. The PAQ score was significantly associated with physical functioning subscore of the PedsQL (r=0.37, p<0.01). Higher physical functioning score was associated with time since transplant (r=0.29, p=0.031). Our SOT cohort has a HRQOL similar to other chronic conditions and higher than previous reported HRQOL in pediatric SOT populations. Higher levels of PA and longer time since transplant are associated with higher physical functioning scores.

Important considerations for drugs, nutritional, and herbal supplements in pediatric solid organ transplant recipients.

Pediatric transplant recipients are on multiple prescription and non-prescription drugs. Many patients also use dietary, nutritional, and herbal supplements. This manuscript researched formulations of immunosuppressive drugs currently available and presents information on generic immunosuppressive drugs, commonly used non-prescription medications, dietary supplements, and herbal supplements. Immunosuppressive drugs are available in various formulations. Not all formulations are interchangeable. A number of FDA-approved generic formulations are available commercially in the United States. Generally generic formulations produce similar blood concentration vs time profiles compared to brand name products in adults and are considered to be bioequivalent. NSAID should be avoided in transplant patients due to potential drug interactions and increased risk associated with NSAID use; and appropriate doses of acetaminophen should be used for treatment of pain. Over-the-counter medications, such as guaifenesin and dextromethorphan, antihistamine medications, including diphenhydramine, loratadine, cetirizine, and fexofenadine, can be safely used in pediatric solid organ transplant population. Many safe and effective over-the-counter options exist for stool softening and as laxative. Diarrhea can lead to an increase in calcineurin inhibitor levels. Food can alter the absorption of immunosuppressive drugs. Several herbal products can alter immune status of the patients or alter the blood concentration of immunosuppressive drugs or may produce renal or hepatic toxicities and should be avoided in pediatric transplant recipients. It is important to educate pediatric transplant recipients and their families about not only immunosuppressive drug therapy but also about non-prescription drugs, dietary, and herbal supplement use.

Physical activity and its correlates in a pediatric solid-organ transplant population.

PA has been shown to have benefits in SOT patients. Studies assessing physical activity levels and its correlates in a pediatric solid-organ transplant population are limited. The aim of this study was to assess PA levels and identify baseline and contemporaneous factors that contribute to PA in a pediatric SOT population. A retrospective cross-sectional review was performed on 58 pediatric transplant patients (16 heart, 29 kidney, and 13 liver transplant). PA was measured by PAQ-C or PAQ-A. Demographics, baseline, and contemporaneous factors were collected. There were no significant differences in baseline and contemporaneous characteristics between heart, kidney, and liver transplant recipients. SOT recipients were 15.2 [12.3-17.3] years old at time of completing the PAQ. Median PAQ score was 2.2 [1.7-2.9]. There were no significant differences in PAQ scores between organ transplant type or between genders. Lower PAQ score was associated with sensory disability (9 vs 49 without disability; P=<.01) and age at time of completing the PAQ (r=-.50, P=<.01). These results suggest that older age at time of completing the PAQ and presence of sensory disability may influence PA levels in the pediatric SOT population.

Underimmunization of the solid organ transplant population: An urgent problem with potential digital health solutions.

Solid organ transplant recipients are at risk for potentially life-threatening infections due to lifelong immunosuppression. Vaccine-preventable infections result in graft injury, morbidity, mortality, and significantly increased medical costs. Unfortunately, the majority of transplant recipients continue to be underimmunized at the time of transplant and thereafter. Given the rising rates of vaccine hesitancy and refusal in the general population, transplant recipients can no longer rely on herd immunity to protect them from vaccine-preventable infections. Novel tools are desperately needed to overcome transplant-specific immunization barriers to improve immunization rates in this high-risk population. Digital health technologies may offer a solution by addressing transplant-specific barriers: specifically, providing accurate information about vaccine safety, efficacy, and timing in the pre- and posttransplant periods; making a complete immunization record universally available and easily accessible; enabling communication between patients and multiple providers; and providing automated vaccine reminders to both patients and providers when vaccines are due using transplant-specific immunization guidelines. Digital health has transformed health care by empowering patients with their own health information and connecting patients, their providers, and public health officials. In doing so, it offers a potential platform to address and overcome the problem of underimmunization in the transplant population.

Patient-reported outcome measures within pediatric solid organ transplantation: A systematic review.

Subjective evaluation of medical care and disease outcomes from patients' perspectives has become increasingly important. Patient-reported outcome measures (PROMs) play a prominent role in engaging patients, capturing their experiences and improving patient care. This systematic review sought to identify PROMs that are used in the field of pediatric solid organ transplantation, with the aim to inform the implementation of PROMs into clinical practice for this population. A systematic review of English language, peer-reviewed articles was performed on key health science databases to identify publications using PROMs in pediatric solid organ transplantation. The search yielded 3670 articles, with a final data set of 62 articles that included 47 different PROMs. The three most frequently used PROMs included the following: (a) PedsQL™ Generic Core Scales (n=25); (b) Children's Depression Inventory (n=6); and (c) Child Health Questionnaire (n=6). Of the 47 PROMs, 42 were generic and five were disease-specific; only six PROMS had a documented psychometric evaluation within a pediatric solid organ transplant population. This review outlines the attributes of the instruments (eg, domains captured), as well as the psychometric properties of those evaluated. PROMs are increasingly used in the field of pediatric transplantation; however, there are limited details in the current literature about their conceptual underpinnings and psychometric properties. This review highlights the need for additional psychometric evaluation of identified measures to establish the necessary foundation to inform the implementation of PROMs into clinical care for pediatric solid organ transplant patients.

Clostridium difficile infection after pediatric solid organ transplantation: a practical single-center experience.

During the last two decades, there has been a worldwide increase in frequency and severity of infections with Clostridium difficile (CDI). Solid organ transplant (SOT) recipients receiving immunosuppressing medications are especially at risk. We collected data from immunocompromised pediatric patients, including kidney and liver transplant recipients, at our tertiary pediatric care center in Germany. For this, we performed a retrospective review of institutional databases and analyzed data from all children who underwent diagnostic tests for CDI in a 3-year study period. A total of 797 diagnostic tests in 343 patients were performed. We found 104 infection episodes in 69 patients (42% female, ages 12days-20years). Children after SOT accounted for 20% of all detected CDI patients in our series. Median time of CDI onset after transplantation was 588days. Overall antibiotic exposure was identified as the major risk factor, particularly in immunocompromised children after SOT (exposure in > 95% of all cases). The occurrence of CDI in the pediatric SOT population contributes to a greater length of stay and higher hospital charges. However, only very few severe complications from CDI were observed in our cohort. A potentially fulminant course of CDI can be prevented in most cases if timely diagnosis and treatment are carried out.

Enhancing education on skin cancer and risk reduction measures in the pediatric solid organ transplant population

Enhancing education on skin cancer and risk reduction measures in the pediatric solid organ transplant population

Cytomegalovirus Infection in Pediatric Solid Organ Transplant Recipients: a Focus on Prevention.

Solid organ transplantation is a life-saving procedure that has changed the prognosis for infants and children with end-stage organ disease. Cytomegalovirus (CMV) is one of the most common infections that occur after organ transplantation in pediatric patients, yet the standard of care for CMV prevention remains unclear. We review the literature regarding CMV disease effects, risk factors, diagnostics, prevention strategies, and antiviral treatment in pediatric solid organ transplantation. This discussion focuses on the current prevention strategies: prophylaxis, preemptive, and hybrid therapy, as well as novel strategies that may help better prevent the CMV disease in the pediatric solid organ transplant population.

Atypical Marginal Zone Hyperplasia is a Mimic for Lymphoma in Pediatric Transplant Recipients: Report of Two Patients

Atypical marginal zone hyperplasia (AMZH) of mucosa-associated lymphoid tissue (MALT) closely resembles lymphoma in that it shows expansion of the marginal zones with prominent intraepithelial B lymphocytes, is immunoglobulin light-chain restricted, and may show aberrant CD43 expression. However, unlike lymphoma, it does not show rearrangement of the immunoglobulin heavy chain gene (immunoglobulin H [IgH]) by polymerase chain reaction (PCR), and it behaves in a benign fashion. We identified AMZH in 2 pediatric solid organ transplant recipients who presented with adenotonsillar hypertrophy. To date, the patients have experienced a self-limited course in the absence of treatment or reduction of immunosuppression. Atypical marginal zone hyperplasia is a pitfall for posttransplant lymphoproliferative disorder and MALT lymphoma in the pediatric solid organ transplant population. In transplant patients with a lambda-restricted B-cell clone and marginal zone hyperplasia in native MALT sites, PCR for IgH and IgK gene rearrangement is essential to prevent misdiagnosis.

Risk factors for adenotonsillar hypertrophy in children following solid organ transplantation

Objective: Post-transplantation lymphoproliferative disorder (PTLD), or its precursor, Epstein-Barr virus (EBV)-related lymphoid hyperplasia, may first present in the tonsils and adenoids in the pediatric solid organ transplant population. We sought to identify signs and symptoms of and risk factors for adenotonsillar hypertrophy (ATH), a potential precursor to PTLD in children following solid organ transplantation. Methods: We performed a cross-sectional study of 132 consecutive pediatric solid organ transplant patients at our institution. Questionnaire, physical examination, and laboratory data collection were obtained. Correlation of signs and symptoms of ATH with objective laboratory data was conducted. Results: 132 pediatric transplant recipients (64 renal, 68 liver) were enrolled. Mean age at transplantation was 7.4 (S.D. 6.0) years with a mean follow-up of 49.0 (S.D. 48.4) months post-transplantation. The mean questionnaire score was 8.4 (S.D. 7.9) out of a maximum 65 and the mean physical examination score was 3.9 (S.D. 1.9) out of a maximum 8, with a statistically significant correlation between the two (Pearson's r=0.352, P<0.001). A multivariate linear regression model found recipient EBV seronegativity and younger age at transplantation to be statistically significant risk factors for development of ATH ( P=0.024 and 0.035, respectively). Conclusions: Young age and EBV seronegativity confer increased risk for ATH in pediatric patients undergoing solid organ transplantation. As ATH may be the earliest sign of PTLD, long-term surveillance is required to determine the impact of ATH on quality of life and survival in these patients.

Adenotonsillar hypertrophy and Epstein-Barr virus in pediatric organ transplant recipients.

Epstein-Barr virus-related (EBV-related) lymphoid hyperplasia of the tonsils and adenoids is a precursor to post-transplantation lymphoproliferative disorder (PTLD). The incidence of post-transplantation adenotonsillar hypertrophy, a potential early sign of PTLD or EBV-related lymphoid hyperplasia, is not known. We sought to identify potential risk factors for adenotonsillar hypertrophy manifested as EBV-related hyperplasia and early PTLD in the pediatric solid organ transplant population. Cross-sectional analysis. We developed a 65-point questionnaire concerning obstructive sleep disorder and upper respiratory tract infections and an 8-point focused physical examination, to identify prevalence of and risk factors for adenotonsillar hypertrophy in the pediatric transplant population. We evaluated 120 pediatric solid organ transplant recipients by parental questionnaire and focused adenotonsillar physical examination. Of the 120 patients, 62 had undergone liver transplantation and 58 had undergone kidney transplantation. Overall, the mean questionnaire score was 8.36 (range, 0-40) and the mean physical examination score was 3.86 (range, 1-8). Patients whose EBV serological test result was negative at the time of transplant had higher scores for both the questionnaire (mean score, 10.24) and the physical examination (mean score, 4.56) than those whose EBV serological test result was positive at the time of transplantation (scores of 7.38 and 3.30 for questionnaire and physical examination, respectively). The difference in examination scores was statistically significant (P <.003). Epstein-Barr virus seronegativity at the time of organ transplantation is a known risk factor for PTLD, with associated risk of developing EBV-related lymphoid hyperplasia. Our results indicate a higher incidence of symptoms and signs consistent with adenotonsillar hypertrophy in the EBV seronegative population. Adenotonsillar hypertrophy may be a precursor to EBV-related lymphoid hyperplasia and PTLD and must be identified in this patient population.