Background: Data on the humoral immune response to standard COVID-19 vaccination are scarce in adolescents and especially in children below 12 years of age with chronic kidney diseases (CKD) including pediatric kidney transplant recipients (KTR).
Methods: We therefore investigated in a two-center retrospective observational cohort study the humoral immune response including live-virus neutralization against the SARS-CoV-2 omicron (BA.1) variant after standard COVID-19 mRNA vaccination in 123 patients with CKD aged 5–30 years at the University Children’s Hospitals in Heidelberg and Cologne (Germany) between April 2021 and April 2022.
Results: Humoral immune response differed significantly (P=0.008) among three patient cohorts: 29 of 77 (37.7%) KTR, 5 of 26 (19.2%) of patients with CKD on immunosuppressive therapy, and 1 of 20 (5%) CKD controls did not respond. The magnitude of the humoral immune response in KTR (median 117 [IQR, 0–769] BAU/mL) was 9-fold lower (P<0.001) than in CKD controls (median 1046 [IQR, 470–2735] BAU/mL). In the total cohort (n=123) and KTR cohort (n=77) children aged 5–11 years had a comparable rate and degree of immune response as adolescents and young adults despite lower vaccine doses (10µg vs. 30µg BNT162b2).
 
Independent risk factors for non-response in the full cohort (n=123) were treatment with two (OR, 9.24; 95% CI, 1.61–175.7) or three or more immunosuppressants (OR, 17.07; 95% CI, 2.91–328.0) and in the subgroup of KTR patients (n=77) an eGFR < 60 mL/min/1.73 m² (OR, 3.44; 95% CI, 1.16 – 11.4), female sex (OR, 3.11; 95% CI, 1.05 – 10.0) and an immunosuppressive regimen in conjunction with MMF compared with everolimus (OR, 0.15; 95% CI, 0.02 - 0.72) or azathioprine (OR, 0.09; 95% CI, 0.01-0.62). After the third vaccination, 8 of 15 (53.3%) previously seronegative KTR turned seropositive but the magnitude of the humoral immune response was lower than in those with a response after two vaccinations (anti-S1-RBD IgG, 120.1 [IQR, 50.8 – 340.6] BAU/mL vs. 506.2 [IQR, 144.7 – 1583] BAU/mL, p=0.036). Of patients with available serum samples and a BAU of ≥ 100/mL, only 10 of 34 (29.4%) showed any neutralizing activity (ID50 ≥1:10) against the omicron (BA.1) variant with a significant positive correlation between the anti-SARS-CoV-2-IgG titer and the corresponding neutralizing activity (R = 0.714, p < 0.001). A ROC analysis revealed an optimal cut-off at 1411 BAU/mL (ROC-AUC, 0.74; 95% CI, 0.54 – 0.95, P= 0.028) with 8 of 16 (50%) patients above but only 2 of 18 (11%) patients below this cut-off showing any live-virus neutralization activity against omicron (BA.1)
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Conclusion: A standard mRNA vaccine regimen in immunosuppressed children and adolescents with CKD and KTR elicit an attenuated humoral immune response. Live-virus neutralization against the omicron variant is achieved in only approx. 10% of immunosuppressed pediatric CKD and KTR patients when extrapolating these data to the entire patient cohort.