Correlates of SARS-CoV-2 Breakthrough Infections in Kidney Transplant Recipients Following a Third SARS-CoV-2 mRNA Vaccine Dose
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants
2.2. SARS-CoV-2 Antibody Measurement
2.3. Antibody Neutralization
2.4. Statistical Analysis
2.5. Machine Learning Models
2.6. National COVID-19 Infection Rates
3. Results
3.1. Clinical and Demographic Characteristics
3.2. Vaccine-Induced SARS-CoV-2 Antibody Response
3.3. Neutralizing Antibodies to Different SARS-CoV-2 Variants and Associations with SARS-CoV-2 Breakthrough Infection
3.4. Immunosuppressive Regimen and Risk of SARS-CoV-2 Breakthrough Infection
3.5. Machine Learning Model Identifying Correlates of SARS-CoV-2 Breakthrough Infection
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | All KTRs (n = 135) | Seropositive After Third Vaccine Dose (n = 100) | Seronegative After Third Vaccine Dose (n = 35) |
---|---|---|---|
Female, n (%) | 55 (41%) | 38 (38%) | 17 (49,6%) |
Age, median years (IQR) | 55 (47–67) | 54 (46–67) | 61 (51–68) |
Vaccine type (%) | |||
3 × BNT162b2 mRNA | 131 (97%) | 98 (98%) | 33 (94.3%) |
3 × mRNA1273 | 4 (3%) | 2 (2%) | 2 (5.7%) |
Time between transplantation and first vaccine dose, years (IQR) | 6.29 (2.85–11.98) | 7.64 (3.97–13.18) | 3.59 (0.71–6.54) |
First transplant, n (%) | 112 (83%) | 81 (81%) | 31 (88.6%) |
Type of immunosuppressive regimen, n (%) | |||
Triple therapy (CNI, antimetabolite, steroids) | 64 (47%) | 38 (38%) | 26 (74%) |
Steroid-free dual therapy * | 40 (29.6%) | 33 (33%) | 7 (20%) |
Antimetabolite-free dual therapy ** | 14 (10.4%) | 13 (13%) | 1 (2.9%) |
CNI-free dual therapy *** | 5 (3.7%) | 4 (4%) | 1 (2.9%) |
Rituximab < 1 year prior to first vaccine dose | 6 (4.4%) | 2 (2%) | 4 (11.4%) |
Immunosuppressive Regimen | All KTRs n (%) | Risk of SARS-CoV-2 Breakthrough Infection, OR | Lower 95% | Upper 95% | Fisher’s Exact Test |
---|---|---|---|---|---|
Triple therapy (CNI + antimetabolite + steroid) | 64 (47.4%) | 2.63 | 1.04 | 6.64 | 0.044 |
Steroid-free dual therapy | 40 (29.6%) | 0.57 | 0.20 | 1.65 | 0.34 |
Antimetabolite-free dual therapy | 14 (10.4%) | 0.75 | 0.16 | 3.59 | 1.00 |
CNI-free dual therapy | 5 (3.7%) | 0.00 | N/A | N/A | 0.59 |
Rituximab < 1 year prior to vaccination | 6 (4.4%) | 0.92 | 0.10 | 8.27 | 1.00 |
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Thygesen, M.V.; Strandhave, C.; Kiib, J.M.; Berg, R.; Andersen, M.S.; Dall, E.B.; Hornstrup, B.G.; Østergaard, H.C.; Mose, F.H.; Gregersen, J.W.; et al. Correlates of SARS-CoV-2 Breakthrough Infections in Kidney Transplant Recipients Following a Third SARS-CoV-2 mRNA Vaccine Dose. Vaccines 2025, 13, 777. https://doi.org/10.3390/vaccines13080777
Thygesen MV, Strandhave C, Kiib JM, Berg R, Andersen MS, Dall EB, Hornstrup BG, Østergaard HC, Mose FH, Gregersen JW, et al. Correlates of SARS-CoV-2 Breakthrough Infections in Kidney Transplant Recipients Following a Third SARS-CoV-2 mRNA Vaccine Dose. Vaccines. 2025; 13(8):777. https://doi.org/10.3390/vaccines13080777
Chicago/Turabian StyleThygesen, Miriam Viktov, Charlotte Strandhave, Jeanette Mølgaard Kiib, Randi Berg, Malene Söth Andersen, Emma Berggren Dall, Bodil Gade Hornstrup, Hans Christian Østergaard, Frank Holden Mose, Jon Waarst Gregersen, and et al. 2025. "Correlates of SARS-CoV-2 Breakthrough Infections in Kidney Transplant Recipients Following a Third SARS-CoV-2 mRNA Vaccine Dose" Vaccines 13, no. 8: 777. https://doi.org/10.3390/vaccines13080777
APA StyleThygesen, M. V., Strandhave, C., Kiib, J. M., Berg, R., Andersen, M. S., Dall, E. B., Hornstrup, B. G., Østergaard, H. C., Mose, F. H., Gregersen, J. W., Jensen-Fangel, S., Bech, J. N., Birn, H., Thomsen, M. K., & Offersen, R. (2025). Correlates of SARS-CoV-2 Breakthrough Infections in Kidney Transplant Recipients Following a Third SARS-CoV-2 mRNA Vaccine Dose. Vaccines, 13(8), 777. https://doi.org/10.3390/vaccines13080777