Pediatric liver transplant (LT) recipients are often transplanted at a young age, precluding them from receiving live virus vaccinations (LVV) such as varicella (VZV) vaccine and measles, mumps and rubella. This places them at profound risk for vaccine preventable illness. We sought to detail safety of vaccination. This was a retrospective cohort study of pediatric LT recipients at two children's hospitals. Among 204 LT recipients included in the study, 97 received at least one LVV after LT. Six patients who did not receive LVV after transplant had evidence of vaccine‐preventable infection following vaccination (one disseminated VZV disease, five VZV‐related rash), while one patient who received LVV after transplant developed a diffuse VZV‐related rash. Rejection rates were the same between those that did and did not receive a live virus vaccine post‐transplant. There were no serious adverse events caused by vaccination post‐transplant. LVV following LT was safe at our two institutions, although there exist limitations in our study due to its retrospective study design. Larger scale studies should be performed to evaluate the effectiveness of LVV in relation to immunosuppression.

The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have been proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on a larger scale, whether the systemic and mucosal anti-commensal responses are redundant or have unique features. To address this gap in knowledge, we developed an integrated host-commensal approach combining microbial flow cytometry and metagenomic sequencing (mFLOW-Seq) to comprehensively define which microbes induce mucosal and systemic antibodies. We coupled this approach with high-dimensional immune profiling to study a cohort of pediatric patients with SIgAD and household control siblings. We found that mucosal and systemic antibody networks cooperate to maintain homeostasis by targeting a common subset of commensal microbes. In IgA-deficiency, we find increased translocation of specific bacterial taxa associated with elevated levels of systemic IgG targeting fecal microbiota. Associated features of immune system dysregulation in IgA-deficient mice and humans included elevated levels of inflammatory cytokines, enhanced follicular CD4 T helper cell frequency and activation, and an altered CD8 T cell activation state. Although SIgAD is clinically defined by the absence of serum IgA, the symptomatology and immune dysregulation were concentrated in the SIgAD participants who were also fecal IgA deficient. These findings reveal that mucosal IgA deficiency leads to aberrant systemic exposures and immune responses to commensal microbes, which increase the likelihood of humoral and cellular immune dysregulation and symptomatic disease in patients with IgA deficiency.

Mammals produce large quantities of mucosal and systemic antibodies that maintain the intestinal barrier, shape the intestinal microbiome and promote lifelong mutualism with commensal microbes. Here, we developed an integrated host-commensal approach combining microbial flow cytometry and 16s rRNA gene sequencing to define the core microbes that induce mucosal and systemic antibodies in pediatric selective Immunoglobulin A (IgA) deficient and household control siblings with CyTOF analysis to determine the impacts of IgA deficiency on host cellular immune phenotype. In healthy controls, mucosal secretory IgA and IgM antibodies coat an overlapping subset of microbes, predominantly Firmicutes and Proteobacteria. Serum IgG antibodies target a similar consortium of fecal microbes, revealing connections between mucosal and systemic antibody networks. Unexpectedly, IgM provides limited compensation for IgA in children lacking intestinal IgA. Furthermore, we find broad systemic immune dysregulation in a subset of children and mice lacking IgA, including enhanced IgG targeting of fecal microbiota, elevated levels of inflammatory and allergic cytokines and alterations in T cell activation state. Thus, IgA tunes systemic interactions between the host and commensal microbiota. Understanding how IgA tunes baseline immune tone has implications for predicting and preventing autoimmune, inflammatory and allergic diseases broadly, as well as providing improved prognostic guidance to patients with IgA deficiency.

Background Cytomegalovirus (CMV) is an important cause of morbidity and mortality in pediatric solid organ transplant (SOT) recipients. However, the impact of asymptomatic CMV infections (ie, DNAemia) on clinical outcomes is not well established. Methods We performed a retrospective cohort study of children undergoing first SOT at our institution from January 2012 to June 2018. We evaluated the epidemiology of CMV infections and performed multivariable Cox regression to assess the association between CMV DNAemia without disease or CMV disease (syndrome or end‐organ disease) on negative outcomes (death, re‐transplantation, or moderate/severe rejection) within the first year after SOT. Results Among 271 individuals, 43 (15.9%) developed ≥1 CMV infection during the first year after SOT. There were 56 unique CMV infections including 14 episodes of CMV disease. In 167 patients offered CMV prophylaxis, only 8 (4.8%) developed their first CMV DNAemia episode while on prophylaxis 32 developed CMV DNAemia after prophylaxis completion; only 1 episode of CMV disease occurred while on antiviral prophylaxis. When accounting for receipt of ATG, oral steroids, and number of immunosuppressives on a given day, CMV disease was more strongly associated with negative outcomes (Hazard Ratio (HR): 3.28, 95% CI: 0.73–14.64; p = .12) than CMV DNAemia without disease (HR 1.42, 95% CI: 0.19– 10.79; p = .74), although not to a statistically significant degree. Conclusions Most CMV infections occurred after completion of antiviral prophylaxis. CMV disease was more strongly associated with negative outcomes than asymptomatic CMV DNAemia and should be the focus of CMV prevention practices.

Objectives: Describe cumulative seroprevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among employees of a large pediatric healthcare system. Design, Setting, and Participants: Prospective observational cohort study open to adult employees at Children’s Hospital of Philadelphia, conducted April 20 – December 17, 2020. Methods: Employees were recruited starting with high-risk exposure groups, utilizing emails, flyers, and announcements at virtual town halls. At baseline, 1-month, 2-month, and 6-month timepoints, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity. Results: 1740 employees were enrolled. At 6-months, cumulative seroprevalence was 5.3%, below estimated community point seroprevalence; seroprevalence was 5.8% and 3.4% among employees with and without direct patient care, respectively. Most participants seropositive at baseline remained positive at follow-up assessments. In post hoc analysis, direct patient care (HR: 1.95, 95% CI: 1.03 to 3.68), Black race (HR: 2.70, 95% CI: 1.24 to 5.87), and exposure to a confirmed case in a non-healthcare setting (HR: 4.32, 95% CI: 2.71 to 6.88) were associated with statistically significant increased risk for seropositivity. Conclusions: Employee SARS-CoV-2 seroprevalence rates remained below the surrounding community’s point prevalence rates. Provision of direct patient care, Black race, and exposure to a confirmed case in non-healthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID waves or other epidemics.