Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease

Abstract

Background Data on humoral immune response to standard COVID-19 vaccination are scarce in adolescent patients and lacking for children below 12 years of age with chronic kidney disease including kidney transplant recipients. Methods We therefore investigated in this retrospective two-center study (DRKS00024668; registered 23.03.2021) the humoral immune response to a standard two-dose mRNA vaccine regimen in 123 CKD patients aged 5–30 years. A live-virus assay was used to assess the serum neutralizing activity against the SARS-CoV-2 omicron (BA.1) variant. Results Children aged 5–11 years had a comparable rate and degree of immune response to adolescents despite lower vaccine doses (10 µg vs. 30 µg BNT162b2). Treatment with two (odds ratio 9.24) or three or more (odds ratio 17.07) immunosuppressants was an independent risk factor for nonresponse. The immune response differed significantly among three patient cohorts: 48 of 77 (62.3%) kidney transplant recipients, 21 of 26 (80.8%) patients on immunosuppressive therapy, and 19 of 20 (95.0%) patients with chronic kidney disease without immunosuppressive therapy responded. In the kidney transplant recipients, immunosuppressive regimens comprising mycophenolate mofetil, an eGFR of < 60 mL/min/1.73 m2, and female sex were independent risk factors for nonresponse. Two of 18 (11.1%) and 8 of 16 (50.0%) patients with an anti-S1-RBD IgG of 100–1411 and > 1411 BAU/mL, respectively, showed a neutralization activity against the omicron variant. Conclusion A standard mRNA vaccine regimen in immunosuppressed children and adolescents with kidney disease elicits an attenuated humoral immune response with effective live virus neutralization against the omicron variant in approximately 10% of the patients, underlying the need for omicron-adapted vaccination. Graphical abstract

Immunologic Response to SARS-CoV-2 Vaccination in Pediatric Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

“…The included studies characteristics are provided in Table 1 [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. All seven selected studies included 254 pediatric and adolescent KTRs, who were naïve to COVID-19 infection, based on prior to vaccination SARS-CoV-2 IgG titers or patient medical history, and who received two doses of the SARS-CoV-2 mRNA vaccine.…”

Reduced Humoral and Cellular Immune Response to Primary COVID-19 mRNA Vaccination in Kidney Transplanted Children Aged 5–11 Years

“…While titer levels after the second vaccination in GN patients receiving CNI did reach same levels as in healthy controls, the humoral response in investigated KTx patients was markedly decreased, and the overall seroconversion rate was 56%. Previously, a humoral response was reported in 62% of Ktx patients [ 6 ]. A reduced capability of primary vaccination to elicit a humoral response was also seen in adult and adolescent patients after solid organ transplantation [ 24 , 25 , 26 ].…”

“…Currently, primary, as well as booster vaccinations, are encouraged for immunosuppressed children [ 3 , 4 ]. However, as only limited data [ 5 , 6 ] on the immunological response to the vaccination exist in this age group, expert-based recommendations have displaced evidence-based recommendations.…”

Prevention and treatment strategies for kidney transplant recipients in the context of long-term existence of COVID-19

“…Furthermore, while the neutralizing activity against Delta and Omicron variants in transplant patients remained low after receiving the third vaccine dose, the Fc-mediated effector function in SOTRs reached a level similar to that of a cohort of healthy individuals ( 104 ). Stich also indicated that while the standard mRNA vaccine regimen could weaken the humoral immune response in immunocompromised children and adolescents with kidney disease, reducing the vaccine dose could result in effective antibodies against Omicron in approximately 10% of patients ( 110 ). In addition, the study revealed that patients who did not develop humoral immune responses after the third vaccine dose either received an immunosuppressive regimen that included MMF or had an inherited T-cell defect disease.…”