ABSTRACT
Background. Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare sequela that typically develops 2-6 weeks after SARS-CoV-2 infection. According to CDC recommendations, children who recover from MIS-C should be vaccinated 90 days after diagnosis, but safety and immunogenicity data are lacking. Our aim was to evaluate the safety and immunogenicity of one dose of the BNT162b2 vaccine in children with a history of MIS-C. Methods. We conducted a longitudinal study of children with MIS-C admitted to Monroe Carell Jr. Children's Hospital at Vanderbilt from 7/11/2020 to 3/23/2022. Children were eligible if they met CDC's MIS-C criteria and had blood collected before and after SARS-CoV-2 vaccination. Clinical data were obtained from medical records and injection site and systemic reactions were recorded for a week following SARS-CoV-2 vaccination via memory aids. IgG against SARS-CoV-2 nucleocapsid (N), spike receptor-binding domain (RBD), and spike extracellular domain (ECD)was detected using an enzyme-linked immunosorbent assay. The first anti-RBD and anti-ECD levels prevaccination and post vaccination were compared using the paired-samples t-test. Results. Seven children were included, of whom five were male and five were non-Hispanic White. The first blood sample was collected 3-44 days following admission. The median age at admission was 15.8 years (IQR, 10.5-14.7 years), and the median time from admission to vaccination was 7 months (IQR, 6-8 months). Five children each had injection site or systemic reactions (Figure 1);the majority were mild or moderate and occurred within 2 days of vaccination. Children were followed for a median of 5.6 months (4.3-6.2 months) postvaccination;none developed MIS-C recurrence. Following vaccination, mean anti-RBD and anti-ECD levels increased by 2.0 (1.2-2.9;p < 0.001) and 1.9 (1.2-2.6;p < 0.001) absorbance units, respectively (Figure 2). A sensitivity analysis excluding children with antibody evidence of reinfection (increase in anti-N level >= 0.5) showed similar results. Conclusion. SARS-CoV-2 vaccination is safe and immunogenic in children with a history of MIS-C, with no documented recurrence of MIS-C-like illness. Further studies are needed to determine the optimal timing, safety, and immunogenicity of vaccination following MIS-C.
ABSTRACT
Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased morbidity and mortality in immunocompromised individuals, including solid organ transplant recipients (SOTR). Despite being excluded from phase 1-3 SARS-CoV-2 vaccine clinical trials, SOTR were identified as high-risk populations and prioritized for vaccination in public health guidelines. We aimed to evaluate the antibody response to two doses of the BNT162b2 (Pfizer-BioNTech) vaccine in SOTR as compared to healthy controls (HC). Methods. SOTR and HC scheduled to receive two doses of BNT162b2 vaccine and able to complete required follow-up visits were enrolled. Blood specimens were collected from participants before receiving the first and second doses and 21-42 days after the second dose. Enzyme-linked immunosorbent assay (ELISA) was used to detect immunoglobulin G (IgG) to the SARS-CoV-2 spike receptor-binding domain (RBD). Generalized estimating equations with a working independence correlation structure were used to compare anti-RBD IgG levels between SOTR and HC at each study visit and within each group over time. All models were adjusted for age, sex, and pre-vaccination seroreactivity in the ELISA. Results. A total of 54 SOTR and 26 HC were enrolled, with mean (SD) ages of 72 (3.6) and 62 (6.7) years, 61% and 35% were male, and 91% and 88% were white, respectively. The most common organ transplant types were kidney (41%) and liver (37%). All SOTR were receiving calcineurin inhibitors. The median time post-transplantation was 7 years. SOTR had markedly lower mean anti-RBD IgG levels when compared to HC with adjusted mean differences of -0.76 (95%CI: [-1.04, -0.47];p < 0.001) ELISA units (EU) and -1.35 (95%CI [-1.68, -1.01];p < 0.001) EU after the first and second doses, respectively (Figure 1). Both groups had a significant increase in anti-SARS-CoV-2 IgG levels after the second dose. However, the magnitude was lower in SOTR, 0.49 (95%CI [0.31, 0.69];p < 0.001) EU than in HCs, 1.08 (95% CI [0.91, 1.24];p < 0.001) EU. Figure 1. Anti-SARS-CoV-2 RBD IgG levels in solid organ transplant recipients and healthy controls before receiving the BNT162b2 vaccine (baseline), post-vaccine dose 1, and post-vaccine dose 2. Conclusion. Our study showed SOTR mounted weaker humoral immune responses than HC to SARS-CoV-2 vaccines. Given a lower response, SOTR should continue to practice social distancing and masking until data on vaccine efficacy are available in this vulnerable population.