Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation.

Publication date: May 26, 2025

Background: Kidney transplant (KTx) recipients exhibit impaired responses to SARS-CoV-2 vaccination. Correlates of vaccine-induced immunity and risk factors for breakthrough infection are not fully defined. This study evaluated the humoral response trajectories and determinants of breakthrough infection in KTx recipients. Methods: KTx recipients received two doses of the BNT162b2 mRNA vaccine three weeks apart and a booster after six months. Patients were categorized based on pre-vaccination status: previous COVID-19 disease (DIS), asymptomatic SARS-CoV-2 infection (INF), or infection-nacEFve (NEG). Serum anti-spike antibody titers were assessed at baseline, before the second dose, and at 1, 3, 6, 9, and 12 months. Linear mixed models and survival analyses were performed. Results: Of 326 enrolled patients, 189 with complete time-point data were included in the longitudinal analysis. Antibodies were detectable in 89% of DIS/INF at baseline and 91% before the second dose, but were negligible in NEG. In NEG, the seropositivity increased after vaccination and booster, reaching 78% at 12 months. Age (-5% per year, p < 0. 001) and BMI (+10% per unit, p = 0. 004) influenced titers; antimetabolites and steroids had strong negative effects (-70%, p = 0. 005; -84%, p = 0. 001). Breakthrough infections occurred in 104 (31. 9%); 40% were asymptomatic, and 2 patients died. An mTOR inhibitor was associated with a reduced infection risk (OR 0. 27 [CI: 0. 09-0. 70], p = 0. 009). Higher antibody titers correlated with delayed infection (p = 0. 063). Conclusions: In KTx patients, humoral response to SARS-CoV-2 vaccination is limited in infection-nacEFve patients but improved by booster dosing; the hybrid immunity is more effective. Immunosuppressive regimens influence the immune response, and mTOR inhibitors may protect against breakthrough infection.

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Concepts Keywords
Antimetabolites BNT162b2
Bnt162b2 COVID
Months hybrid immunity
Transplant immune response
Vaccination infection risk
kidney transplant
mRNA vaccine
SARS-CoV-2

Semantics

Type Source Name
disease MESH Breakthrough Infection
disease MESH COVID-19
pathway REACTOME SARS-CoV-2 Infection
disease MESH infection
disease IDO immune response
disease MESH hepatitis
disease MESH diabetes mellitus
disease MESH hypertension
disease MESH cardiovascular diseases
disease MESH lung disease
disease MESH obesity
disease IDO susceptibility
disease MESH virus infections
disease MESH cancers
disease MESH seroconversion
disease MESH respiratory failure
disease IDO hospital facility
disease IDO blood
disease IDO assay
disease IDO history
drug DRUGBANK Methionine
disease MESH Kidney disease
disease MESH Glomerulonephritis
disease MESH Diabetic nephropathy
disease MESH Immune diseases
disease MESH ADPKD
disease MESH reinfection
disease MESH tics

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