Immunogenicity, Safety, and Clinical Effectiveness After 2 Doses of BNT162b2 Vaccine Among Pediatric Kidney Transplant Recipients Versus Healthy Volunteers: A Prospective Nonrandomized Study

mRNA vaccines are safe and effective in reducing transmission and preventing severe COVID-19 in the pediatric general population.1 This study assessed the immunogenicity, safety, and clinical effectiveness of the BNT162b2 mRNA vaccine in a large cohort of pediatric kidney transplant (KT) recipients versus healthy pediatric volunteers. The study was approved by the local ethics committee. All patients signed a written informed consent form. All KT recipients aged 12 to 18 y old on August 30, 2021, living in the state of Sao Paulo, and in follow-up at the transplant center were invited. The comparator group consisted of healthy child volunteers from a city in the state of Sao Paulo that has acted as a comparator group since the beginning of the pandemic.2 Patients were included if they had received the first dose and were able to receive the second dose, had no confirmed COVID-19 before the first dose, and had not received any other vaccine in the previous 4 wk. Significant adverse events and breakthrough infections were monitored for 6 mo following the second dose. Immunogenicity was assessed at least 28 d following the second dose. When available, serum samples following the first dose were also analyzed. IgG antibodies were measured by the AdviseDx SARS-CoV-2 IgG II assay (Abbott Laboratories, Abbott Park, IL).3 The study included 78 KT recipients and 103 healthy volunteers. They were predominantly male, with a median age of 15 y (interquartile range [IQR] 14–16) in the KT group and 14 y (IQR 13–15) among healthy volunteers (P < 0.0001). The predominant immunosuppressive regimen was tacrolimus/prednisone/azathioprine (69%). Four patients received high-dose pulse methylprednisolone treatment for acute allograft rejection in the past 6 mo, and 1 patient was on plasmapheresis and rituximab for recurrent focal sclerosing glomerulonephritis (Table S1, SDC, https://links.lww.com/TP/C663). IgG-seroprevalence after the second vaccine dose was 91% among the KT recipients and 100% in healthy volunteers (P = 0.002). Median antibody levels were similar (10 240 [IQR 2239–24 411] AU/mL versus 13 771 [IQR 6504–24 894] AU/mL, P = 0.168; Figure 1). The interval between vaccination and laboratorial analysis was 32 d (IQR 27–52) in KT recipients and 109 d (IQR 103–111) among healthy volunteers (P < 0.0001).FIGURE 1.: Survival free from COVID-19 among healthy volunteers (ocean blue), kidney transplant recipients with a vaccine response (orange), and kidney transplant recipients with no vaccine response after the second dose of the BNT161b2 vaccine (magenta). Cox proportional hazards regression model.Before the second vaccine dose, 38 (72%) of the 53 KT recipients with available samples and all the healthy volunteers were seroprevalent for IgG anti–SARS-CoV-2 antibodies (P < 0.0001). Median antibody levels were 1453 (IQR 775–5464) and 5641 (IQR 549–14 919) AU/mL, respectively (P = 0.014; Figure S1, SDC, https://links.lww.com/TP/C663). Seven KT recipients did not develop any antibody responses after vaccination. Median age (16 versus 15 y, P = 0.762), length posttransplant (2.5 versus 4 y, P = 0.304), and proportion of patients on mycophenolate (28% versus 13%, P = 0.283) were all comparable with the seroprevalent ones. Those with no humoral response were more frequently submitted to increased immunosuppression in the previous 6 mo (28% versus 4%, P = 0.012). There were no severe adverse events in any groups following vaccination. No KT recipients experienced acute allograft rejection. All COVID-19 cases occurred after January 3, 2022, and at least 27 d after the second vaccine dose. Seven (8.9%) KT recipients developed a breakthrough infection after 53 d (IQR 44–115) from the second dose, 2 of them without a vaccine response. None required hospitalization or changes in the immunosuppressive regimen. Among the healthy volunteers, there were 8 (7.7%) breakthrough infections after 78 d (IQR 71–88) from the second dose, without hospitalizations. Clinical presentation was similar between the 2 groups. Taking the healthy volunteers as a reference, the risk of breakthrough infections in 180 d was similar in KT recipients with a vaccine response (hazard ratio 1.42 [95% confidence interval, 0.41-4.93]) but higher in those with no IgG response (hazard ratio 6.95 [95% confidence interval, 1.33-36.1], Figure 1). In conclusion, this study demonstrated that the 2-dose coronavirus mRNA vaccination regimen was associated with a high seroprevalence rate among pediatric KT recipients, although lower than in the healthy pediatric volunteers. The relationship between vaccine response and protection against COVID-19 in KT recipients suggests the relevance of immunization in this population. The interval between vaccination and serological evaluation was different in the 2 groups, which may have interfered with the comparison of antibody values. The proportion of patients on mycophenolate was smaller than in previous studies,4,5 limiting the generalizability of the data.