Current CDC guidelines have shifted to a three-part series including bivalent vaccine doses in pediatric patients (33)

Current CDC guidelines have shifted to a three-part series including bivalent vaccine doses in pediatric patients (33). pediatric PAD patients compared to adult PAD patients (2,890.7 vs. 140.1 U/mL; p<0.0001). Pediatric PAD patients with low class-switched memory B-cells, defined as <2% of total CD19+ B-cells, had significantly lower mean anti-SARS-CoV-2-spike antibody levels than those without (p=0.02). Following a third-dose monovalent SARS-CoV-2 immunization, the mean anti-SARS-CoV-2-spike antibody levels in pediatric PAD patients significantly increased (2,890.7 to 18,267.2 U/mL; 25-hydroxy Cholesterol p<0.0001). These data support Centers for Disease Control guidelines regarding three-part SARS-CoV-2 vaccine series, including in the pediatric PAD patient demographic. Keywords: COVID-19, vaccine, predominantly antibody deficiency, SARS-CoV-2, inborn error of immunity, primary immune deficiency Introduction Predominantly antibody deficiency (PAD) is the most commonly diagnosed inborn error of immunity (IEI) and the most frequent symptomatic primary immunodeficiency disorder world-wide. PAD encompasses a heterogeneous collection of disorders characterized by increased susceptibility 25-hydroxy Cholesterol to infections, low immunoglobulin levels, and impaired vaccine responses (1). The clinical presentation can be variable, ranging from mild symptoms to severe complications. Patients with PAD are at risk of ongoing disease progression, development of autoimmunity, end-organ damage, and reduced life expectancy (2). Studies have demonstrated that children produce IMMT antibody long-term antibody responses to COVID-19 infection (3). Healthy children are less likely to have severe COVID-19 compared to adults (4, 5). Multiple studies have demonstrated worse COVID-19 infection outcomes and more severe disease in children who had received immunosuppressant medication or had an immunocompromising condition such as cancer compared to healthy 25-hydroxy Cholesterol children (6C8). There have been several studies investigating COVID-19 infection outcomes in patients with IEI. A review of the Italian Primary Immunodeficiency Network found that there were no deaths among 33 COVID-19 positive children with an underlying IEI condition (9). Abolhassani et al. found that among 381 published cases of COVID-19 infection in pediatric IEI patients, 23.6% of them had severe COVID-19, with an overall mortality rate of 8.7% (10). The trials evaluating the safety and effectiveness of the SARS-CoV-2 vaccine in children and adolescents excluded those who had immunodeficiency diseases including PAD (11, 12). Subsequent evaluation of the effectiveness of the SARS-CoV-2 vaccine in adult primary immune deficiency patients found lower humoral immune responses in adult PAD patients when compared to healthy controls (13C15). To date, most studies regarding the efficacy of the SARS-CoV-2 vaccine in immunocompromised children are limited to those receiving immunosuppressants for a medical condition such as renal disease, malignancy, or organ transplant (16, 17). Among IEI patients, Erra et?al. described the safety and efficacy of a two-dose mRNA vaccine series in adolescent IEI patients ages 12 years and older and showed that SARS-CoV-2 vaccine immunogenicity after a two-dose series was lower in pediatric IEI patients when compared to healthy controls (18). However, there is limited data regarding efficacy of a third dose of the monovalent SARS-CoV-2 vaccine in pediatric patients with PAD. The aim of this study was to assess the efficacy of the SARS-CoV-2 vaccine, following two-dose initial series and third-dose boost, in pediatric patients of all ages with PAD. Methods This study was performed at Mass General Brigham under an institutional review boardCapproved protocol (No. 2021P002414). Antibody response to the SARS-CoV-2 vaccine in patients with known PAD was evaluated. Pediatric PAD patients who received an initial two-dose SARS-CoV-2 vaccine series between May 2021 and September 2022 were included. The PAD diagnoses were confirmed by manual chart review by a medical immunologist and met consensus meanings for PAD (19C21). Individuals with main PAD were further subclassified as slight (including IgG subclass deficiency, specific antibody deficiency (SAD), and main hypogammaglobulinemia), moderate (including uncomplicated common variable immune deficiency (CVID), defined as an absence of co-occurring autoinflammatory medical features), and severe (including complicated CVID/SAD, defined as the presence of concomitant autoinflammatory medical features) (22). Individuals with confounding variables at the time of immunodeficiency analysis (e.g., ongoing immunosuppression without the potential for discontinuation) were considered as secondary PAD. We.

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