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. 2023 Jun;38(6):1935-1948.
doi: 10.1007/s00467-022-05806-9. Epub 2022 Nov 21.

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

Maximilian Stich  1 , Veronica Di Cristanziano  2 , Burkhard Tönshoff  1 , Lutz Thorsten Weber  3 , Jörg Dötsch  3 , Marian Theodor Rammer  3 , Susanne Rieger  1 , Eva Heger  2 , Sven F Garbade  1 , Kathrin Burgmaier  3   4 , Louise Benning  5 , Claudius Speer  5 , Sandra Habbig #  6 , Sophie Haumann #  3
Affiliations

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

Maximilian Stich et al. Pediatr Nephrol. 2023 Jun.

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. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: COVID-19; Coronavirus; Pediatric nephrology; SARS-CoV-2; Transplantation.

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Conflict of interest statement

LTW and SH participated in an advisory board and received a compensation from BioNTech. All the other authors have indicated they have no potential conflicts of interest to disclose.

Figures

None
A higher resolution version of the Graphical abstract is available as Supplementary information
Fig. 1
Fig. 1
Disposition of study participants. *Five kidney transplant recipients experienced a RT-PCR-proven SARS-CoV-2 infection. BAU, binding antibody units; KTR, kidney transplant recipients; RBD, receptor binding domain
Fig. 2
Fig. 2
Anti-SARS-CoV-2 S1-RBD-IgG (BAU/mL) on a log10-scale after a standard two-dose COVID-19 mRNA vaccine regimen. Panel a data stratified according to the three patient cohorts and panel b data stratified according to the number of immunosuppressive agents. The respective median is indicated by a straight line. P-values are calculated using a Mann–Whitney U-test with Holm–Bonferroni correction and are only displayed when P < 0.1. KTR, kidney transplant recipients; CKD-IS, patients with chronic kidney disease on immunosuppressive therapy; CKD, patients with chronic kidney disease without immunosuppressive therapy
Fig. 3
Fig. 3
Subgroup analysis of anti-SARS-CoV-2 S1-RBD IgG (BAU/ml) in kidney transplant recipients (KTR) after standard SARS-CoV-2 vaccination according to age category (a), sex (b), eGFR (c), and immunosuppressive regimen (d) on a log10-scale. The median is indicated by a straight line. P-values are calculated using a Mann–Whitney U-test with Holm–Bonferroni correction and are only displayed when P < 0.1
Fig. 4
Fig. 4
Live-virus neutralization of BA.1 (omicron) stratified by patient cohort (a) and anti-S1-RBD IgG level of 100–1411 BAU/mL and > 1411 BAU/mL (b) on a log10-scale with a cut-off for this assay of 1:10. P-values are calculated using a Mann–Whitney U-test with Holm–Bonferroni correction and are only displayed when P < 0.1. KTR, kidney transplant recipients; CKD-IS, patients with chronic kidney disease on immunosuppressive therapy; CKD, patients with chronic kidney disease without immunosuppressive therapy
See this image and copyright information in PMC

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