The Influence of Initial Immunosuppression on the Kinetics of Humoral Response after SARS-CoV-2 Vaccination in Patients Undergoing Kidney Transplantation
Abstract
:1. Introduction
2. Material and Methods
2.1. Study Design and Population
2.2. Primary Endpoint
2.3. Secondary Endpoints
2.4. Immunogenicity Assessment
2.5. Vaccines and Vaccination Strategy
2.6. Immunosuppressive Therapy
2.7. Statistical Analysis
3. Results
3.1. Demographic Characteristics
3.2. Primary Endpoint
3.3. Secondary Endpoints
3.4. Neutralizing Antibodies
3.5. Vaccines
3.6. Clinical Outcomes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
CKD | Chronic Kidney Disease |
CIT | Cold Ischemia Time |
COVID-19 | Coronavirus Disease 2019 |
ECD | Expanded Criteria Donor |
HLA | Human Leukocyte Antigen |
KDPI | Kidney Donor Profile Index |
KDRI | Kidney Donor Risk Index |
KTR | Kidney Transplant Recipient |
IgG | Immunoglobulin G |
M | Month |
mTORi | Mammalian Target Of Rapamycin Inhibitor |
PRA | Panel-reactive Antibody |
rATG | Rabbit Anti-thymocyte Globulin |
SARS-CoV-2 | Severe Acute Respiratory Syndrome Coronavirus 2 |
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Total N = 221 | Transplant N = 113 | Dialysis N = 108 | p | |
---|---|---|---|---|
Age, years (IQR) | 49.9 (38.0–59.5) | 45.4 (35.7–58.2) | 54.0 (43.3–62.5) | <0.001 |
Male sex, N (%) | 124 (56.1) | 62 (54.9) | 62 (57.4) | 0.704 |
Race, N (%) | 0.708 | |||
White | 138 (62.4) | 71 (62.8) | 67 (62.0) | |
Black | 21 (9.5) | 9 (8.0) | 12 (11.1) | |
Other | 62 (28.1) | 33 (29.2) | 29 (26.9) | |
Hypertension, N (%) | 186 (84.2) | 93 (82.3) | 93 (86.1) | 0.438 |
Diabetes mellitus, N (%) | 53 (24.0) | 24 (21.2) | 29 (26.9) | 0.329 |
CKD ethiology, N (%) | 0.291 | |||
Undetermined | 72 (32.6) | 41 (36.6) | 31 (28.7) | |
Glomerulonephitis | 59 (26.7) | 32 (28.3) | 27 (25.0) | |
Diabetes Mellitus | 40 (18.1) | 21 (18.6) | 19 (18.1) | |
Polycystic Kidney Disease | 20 (9.0) | 8 (7.1) | 12 (11.1) | |
Hypertension | 18 (8.1) | 5 (4.4) | 13 (12.0) | |
Urologic | 12 (5.4) | 6 (5.3) | 6 (5.6) | |
Dialysis vintage, months (IQR) | 33.6 (15.1–76.9) | 25.1 (12.9–47.4) | 51.9 (17.7–98.8) | <0.001 |
Dialysis modality, N (%) | 0.019 | |||
Hemodialysis | 183 (82.8) | 90 (79.6) | 93 (86.1) | |
Peritoneal Dialysis | 30 (13.6) | 15 (13.3) | 15 (13.9) | |
Preemptive | 8 (3.6) | 8 (7.1) | - | |
HLA Mismatch (ABDR), N (IQR) | - | 2 (1–3) | - | - |
PRA > 0, N (%) | - | 21 (18.6) | - | - |
Immunosuppression, N (%) | - | |||
Pred + TAC + MPS | - | 66 (58.4) | - | |
Pred + TAC + AZA | - | 45 (39.8) | - | |
Pred + TAC + mTORi | - | 2 (1.8) | - |
IgG Status | Transplant | Dialysis | p | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Screening | M1 | M3 | M6 | M12 | Screening | M1 | M3 | M6 | M12 | Transplant | Dialysis | |
Entire population | ||||||||||||
Seroreversion, N (%) | 0/107 (0.0) | 1/102 (1.0) | 0/101 (0.0) | 0/101 (0.0) | 0/97 (0.0) | 0/102 (0.0) | 1/95 (1.1) | 1/93 (1.1) | 1/91 (1.1) | 0/82 (0.0) | ||
Adjusted population | 0.406 | 0.663 | ||||||||||
Seroreversion, N (%) | 0/94 (0.0) | 1/94 (1.1) | 0/94 (0.0) | 0/94 (0.0) | 0/94 (0.0) | 0/78 (0.0) | 1/78 (1.3) | 1/78 (1.3) | 1/78 (1.3) | 0/78 (0.0) |
Model 1 | Model 2 * | |||
---|---|---|---|---|
Coefficient (CI 95%) | p | Coefficient (CI 95%) | p | |
Transplant–Screening (ref. Dialysis) | 1390 (−2372 to 5152) | 0.469 | 2432 (−1348 to 6213) | 0.207 |
Time (All patients; ref. Screening) | 0.005 | 0.006 | ||
M1 | 2125 (−908 to 5158) | 0.170 | 2.102 (−932 to 5136) | 0.174 |
M3 | 1981 (−1073 to 5035) | 0.204 | 1900 (−1156 to 4955) | 0.223 |
M6 | 5072 (1998 to 8147) | 0.001 | 4980 (1905 to 8056) | 0.002 |
M12 | −474 (−3652 to 2704) | 0.770 | −530 (−3708 to 2649) | 0.744 |
Group + time interaction | 0.005 | 0.006 | ||
Transplant-M1 | −5998 (−10,221 to −1.775) | 0.005 | −5951 (−10,175 to −1726) | 0.006 |
Transplant-M3 | −4288 (−8533 to −42) | 0.048 | −4200 (−8448 to 47) | 0.053 |
Transplant-M6 | −7201 (−11,462 to −2941) | 0.001 | −7100 (−11,362 to −2839) | 0.001 |
Transplant-M12 | −1690 (−6051 to 2670) | 0.447 | −1629 (−5991 to 2732) | 0.464 |
Model 1 | Model 2 * | |||
---|---|---|---|---|
OR (CI 95%) | p | OR (CI 95%) | p | |
Transplant (ref. Dialysis) | 2.40 (0.40 to 14.46) | 0.339 | 4.35 (0.60 to 31.35) | 0.145 |
Time (All patients; ref. screening) | 0.022 | 0.027 | ||
M1 | 1.35 (0.35 to 5.13) | 0.662 | 1.34 (0.36 to 5.06) | 0.665 |
M3 | 1.37 (0.36 to 5.18) | 0.647 | 1.34 (0.35 to 5.05) | 0.667 |
M6 | 7.30 (1.35 to 39.66) | 0.021 | 6.98 (1.29 to 37.91) | 0.024 |
M12 | 23.73 (2.71 to 207.43) | 0.004 | 22.38 (2.56 to 195.35) | 0.005 |
Group + time interaction | 0.832 | 0.812 | ||
Transplant-M1 | 0.68 (0.09 to 5.07) | 0.703 | 0.67 (0.09 to 5.08) | 0.700 |
Transplant-M3 | 0.71 (0.10 to 5.25) | 0.734 | 0.71 (0.10 to 5.37) | 0.744 |
Transplant-M6 | 5.67 (0.15 to 209.70) | 0.346 | 6.23 (0.16 to 237.37) | 0.325 |
Transplant-M12 | 1.73 (0.04 to 80.79) | 0.779 | 1.93 (0.04 to 91.76) | 0.739 |
Total N = 221 | Transplant N = 113 | Dialysis N = 108 | p | |
---|---|---|---|---|
COVID-19, N (%) | 53 (24.0) | 37 (32.7) | 16 (14.8) | 0.002 |
Death, N (%) | 12 (5.4) | 6 (5.3) | 6 (5.6) | 0.936 |
Cause of death, N (%) | 0.241 | |||
Infections other than COVID-19 | 5 (41.7) | 3 (50.0) | 2 (33.3) | |
Cardiovascular | 4 (33.3) | 1 (16.7) | 3 (50.0) | |
COVID-19 | 2 (16.7) | 2 (33.3) | 0 (0.0) | |
Other | 1 (8.3) | 0 (0.0) | 1 (16.7) | |
Hospitalization, N (%) | 85 (38.5) | 58 (51.3) | 27 (25.0) | <0.001 |
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Share and Cite
Foresto, R.D.; Souza, R.M.; dos Anjos, G.R.; Nakamura, M.R.; Goulart, H.d.S.; Sampaio, R.; França, D.P.; Marques, E.F.; Lucena, E.F.; Cristelli, M.P.; et al. The Influence of Initial Immunosuppression on the Kinetics of Humoral Response after SARS-CoV-2 Vaccination in Patients Undergoing Kidney Transplantation. Vaccines 2024, 12, 1135. https://doi.org/10.3390/vaccines12101135
Foresto RD, Souza RM, dos Anjos GR, Nakamura MR, Goulart HdS, Sampaio R, França DP, Marques EF, Lucena EF, Cristelli MP, et al. The Influence of Initial Immunosuppression on the Kinetics of Humoral Response after SARS-CoV-2 Vaccination in Patients Undergoing Kidney Transplantation. Vaccines. 2024; 12(10):1135. https://doi.org/10.3390/vaccines12101135
Chicago/Turabian StyleForesto, Renato Demarchi, Roberto Matias Souza, Gustavo Rodrigues dos Anjos, Mônica Rika Nakamura, Haryanne de Souza Goulart, Rayra Sampaio, Daniela Pereira França, Emanuelle Ferreira Marques, Elisabeth França Lucena, Marina Pontello Cristelli, and et al. 2024. "The Influence of Initial Immunosuppression on the Kinetics of Humoral Response after SARS-CoV-2 Vaccination in Patients Undergoing Kidney Transplantation" Vaccines 12, no. 10: 1135. https://doi.org/10.3390/vaccines12101135