Determinants of Immune Response to Anti-SARS-CoV-2 mRNA Vaccines in Kidney Transplant Recipients: A Prospective Cohort Study

Maria Magicova, Ivan Zahradka, Martina Fialova, Tomas Neskudla, Jiri Gurka, Istvan Modos, Michal Hojny, Petr Raska, Petr Smejkal, Ilja Striz, Ondrej Viklicky, Maria Magicova, Ivan Zahradka, Martina Fialova, Tomas Neskudla, Jiri Gurka, Istvan Modos, Michal Hojny, Petr Raska, Petr Smejkal, Ilja Striz, Ondrej Viklicky

Abstract

Background: Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been recently shown to be impaired in kidney transplant recipients (KTRs), but the underlying factors affecting vaccine effectiveness need to be further elucidated.

Methods: In this prospective cohort study, antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%) in 736 KTRs, who were previously either naive or infected with SARS-CoV-2 and vaccinated before or after transplantation. Cellular response was analyzed in a subset of patients using an interferon gamma release assay (cutoff 0.15 IU/mL, sensitivity 92%, and specificity 100%).

Results: Seroconversion was significantly more impaired in SARS-CoV-2-naive KTRs than in those previously infected (40.1% versus 97.1%; P < 0.001). Mycophenolate use (odds ratio, 0.15; 95% confidence interval, 0.09-0.24; P < 0.001) and depleting therapy in the past year (odds ratio, 0.19; 95% confidence interval, 0.05-0.8; P = 0.023) were found to be among independent factors associated with impaired humoral response. Similarly, the interferon gamma release assay tested in 50 KTRs (cutoff 0.15 IU/mL, sensitivity 92%, specificity 100%) showed that specific T-cell responses against spike protein epitopes are impaired in SARS-CoV-2-naive KTRs, as compared to previously infected KTRs (9.4% versus 90%, P < 0.001). All 35 KTRs vaccinated on the waiting list before transplantation exhibited sustained seroconversion persisting after transplantation.

Conclusions: Survivors of coronavirus disease 2019 and those vaccinated while on the waiting list exhibited a marked immune response to mRNA vaccines, contrary to poor response in naive KTRs vaccinated after transplantation (NCT04832841).

Conflict of interest statement

The authors declare no conflicts of interest.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
FIGURE 1.
FIGURE 1.
Study flowchart. A total of 753 KTRs were enrolled in the study between March 18, and June 3, 2021. Seventeen KTRs with SARS-CoV-2 infection verified by PCR test between the first vaccine dose and antibody testing were excluded from the study. Overall, 736 KTRs were eligible for this study. Participants were further divided according to predefined categories. Of the 41 KTRs vaccinated while on the waiting list, only 6 KTRs had a history of SARS-CoV-2 infection and were not used in the analysis. The other 35 virus-naive KTRs were analyzed for humoral immunity, with 8 of them also tested for cellular immunity. Of the 695 KTRs vaccinated posttransplant, 69 KTRs were previously infected with SARS-CoV-2, whereas 626 had no history of infection. KTR, kidney transplant recipient; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
FIGURE 2.
FIGURE 2.
Anti–SARS-CoV-2 IgG levels according to previous virus infection and transplantation status. KTRs were divided into predefined groups according to the timing of the vaccination with regards to transplantation and previous SARS-CoV-2 infection to (1) KTRs vaccinated before transplant, all of whom were all SARS-CoV-2 naive; (2) SARS-CoV-2–infected KTRs vaccinated posttransplant; and (3) SARS-CoV-2–naive KTRs vaccinated posttransplant. Statistical differences were assessed using the Kruskal-Wallis test; P < 0.001 for the overall model. Post hoc test revealed significant differences between the following groups: 1 and 2, P = 0.019; 1 and 3, P < 0.001; and 2 and 3, P < 0.001. IgG, immunoglobulin G; KTR, kidney transplant recipient; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
FIGURE 3.
FIGURE 3.
Anti–SARS-CoV-2 IgG levels over time. KTRs vaccinated after transplantation in whom seroconversion after the second dose of mRNA vaccine was observed were divided according to previous SARS-CoV-2 infection status and time from the second dose to antibody testing into 3 intervals (60 d from the second dose to testing, respectively). Lower antibody levels were observed in SARS-CoV-2–naive KTRs tested >60 d in comparison with P = 0.035). IgG, immunoglobulin G; KTR, kidney transplant recipient; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
FIGURE 4.
FIGURE 4.
Impact of COVID-19 symptoms on anti–SARS-CoV-2 IgG levels after vaccination. KTRs who received vaccination after contracting SARS-CoV-2 were divided on the basis of the severity of clinical symptoms scored according to the Clinical Spectrum of SARS-CoV-2 Infection definition. Statistical differences were assessed using the Kruskal-Wallis test; P = 0.049 for the overall model. Post hoc test revealed significant differences between asymptomatic KTRs and KTRs with moderate to severe symptoms (P = 0.014). The differences between the other groups were not significant (P = 0.093 for asymptomatic and mild symptoms, and P = 0.168 for mild and moderate to severe symptoms). COVID-19, coronavirus disease 2019; IgG, immunoglobulin G; KTR, kidney transplant recipient; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

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Source: PubMed

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