Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design, Participants, Data Collection
2.2. Collection of Blood Samples and Immunoassays
2.3. Statistical Analysis
2.3.1. Descriptive Statistics
2.3.2. Unsupervised Classification
2.3.3. Penalized Logistic Regression
3. Results
3.1. Characteristics of the Study Population and Outcomes
3.2. Patients Stratification Based on Early T Cells Responsiveness
3.3. Characteristics and Outcomes of Low and High T Cell Responders
3.4. Variables Associated with the Risk to Progression to Severe Pneumonia
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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Baseline characteristics | |
Age, years | 51.7 (16.9) |
Males | 33 (73%) |
Comorbidities | |
Diabetes | 9 (20%) |
Hypertension | 41 (91%) |
Cardiovascular events | 4 (9%) |
BMI > 30 kg/m² | 10 (22%) |
COPD | 1 (2%) |
Time since transplantation, months | 35 (1–400) |
Prior renal transplantation | 4 (9%) |
Pretransplant Donor Specific Antibodies | 0 (0%) |
Baseline creatininemia, µmol/L | 127.5 (79.6–460.0) |
Baseline eGFR, mL/min/1.73 m² | 49.0 (13.0–120.0) |
Immunosuppressive therapy at inclusion | |
Corticosteroids | 34 (76%) |
Calcineurin inhibitors | 43 (96%) |
Antimetabolites | 37 (82%) |
mTOR inhibitors | 3 (7%) |
Presentation at inclusion | |
Time since symptoms onset, days | 5.8 (2.1) |
Fever | 11 (24%) |
Cough | 16 (36%) |
Dyspnea with normal oxygen saturation | 8 (18%) |
Anosmia/ageusia | 11 (24%) |
Diarrhea | 8 (18%) |
Headache | 16 (36%) |
Serum creatinine, µmol/L | 142.1 (79.5–398.0) |
Lymphocytes count, ×109/L | 0.9 (0.2–3.7) |
Residual tacrolemia, µg/L * | 7.19 (2.30–18.40) |
Clinical course | |
Progression to severe pneumonia | 11 (24%) |
Subsequent ICU admission | 2 (4%) |
Death | 1 (2%) |
Low T cell responders (n = 31) | High T cell responders (n = 14) | p-value | |
---|---|---|---|
Baseline characteristics | |||
Age, years | 53.0 (17.3) | 48.9 (16.1) | 0.45 |
Males | 22 (71%) | 11 (79%) | 0.73 |
Comorbidities | |||
Diabetes | 7 (23%) | 2 (14%) | 0.70 |
Hypertension | 27 (87%) | 14 (100%) | 0.29 |
Cardiovascular events | 2 (6%) | 2 (14%) | 0.58 |
BMI> 30 kg/m² | 7 (23%) | 3 (21%) | >0.99 |
Time since transplantation, months | 21 (1–400) | 57 (10–186) | 0.13 |
Prior renal transplantation | 2 (6%) | 2 (14%) | 0.58 |
Baseline creatininemia, µmol/L | 120.0 (79.6–460.0) | 145.5 (94.0–195.0) | 0.42 |
Baseline eGFR, mL/min/1.73 m² | 53.0 (13.0–64.0) | 43.5 (28.0–85.0) | 0.57 |
Immunosuppressive therapy at inclusion | |||
Corticosteroids | 23 (74%) | 11 (79%) | >0.99 |
Calcineurin inhibitors | 30 (97%) | 13 (93%) | 0.53 |
Antimetabolites | 28 (90%) | 9 (64%) | 0.08 |
mTOR inhibitors | 2 (6%) | 1 (7%) | >0.99 |
Presentation at inclusion | |||
Time since symptoms onset, days | 5.8 (2.1) | 5.6 (2.2) | 0.78 |
Fever | 9 (29%) | 2 (14%) | 0.46 |
Cough | 11 (35%) | 5 (36%) | >0.99 |
Dyspnea with normal oxygen saturation | 6 (19%) | 2 (14%) | >0.99 |
Anosmia/ageusia | 7 (23%) | 4 (29%) | 0.72 |
Diarrhea | 5 (16%) | 3 (21%) | 0.69 |
Headache | 9 (29%) | 7 (50%) | 0.20 |
Serum creatinine, µmol/L | 142.1 (79.5–398.0) | 141.4 (94.0–231.8) | 0.67 |
Lymphocytes count, ×109/L | 0.8 (0.2–3.7) | 1.1 (0.3–2.9) | 0.31 |
Residual tacrolemia, µg/L * | 9.05 (4.46) | 7.26 (1.66) | 0.50 |
Immunosuppression management | |||
Antimetabolites withdrawal | 16/28 (57%) | 4/9 (44%) | 0.70 |
Clinical course | |||
Progression to severe pneumonia | 11 (35%) | 0 (0%) | 0.01 |
Median ORs | %95 CI | VIP | |
---|---|---|---|
High T cell responsiveness (cluster 1) | 0.43 | [0.05–1.00] | 0.85 |
Low T cell responsiveness (cluster 2) | 3.00 | [1.53–39.10] | 0.98 |
Age (years) | 0.86 | [0.12–1.87] | 0.58 |
Sex (Female) | 0.63 | [0.13–2.31] | 0.65 |
Sex (Male) | 1.49 | [0.47–6.72] | 0.62 |
BMI (kg/m²) | 1.28 | [0.48–4.32] | 0.68 |
Time since transplantation (years) | 0.69 | [0.14–1.40] | 0.68 |
Basal creatinemia (µmoL/L) | 2.06 | [1.13–9.21] | 0.97 |
Diabetes (No) | 0.43 | [0.02–1.49] | 0.84 |
Diabetes (Yes) | 1.73 | [0.66–33.09] | 0.75 |
Calcineurin inhibitor (No) | 0.52 | [0.08–0.95] | 0.57 |
Calcineurin inhibitor (Yes) | 1.83 | [1.00–10.18] | 0.53 |
mTOR inhibitor (No) | 1.13 | [0.32–3.58] | 0.37 |
mTOR inhibitor (Yes) | 0.97 | [0.37–2.90] | 0.37 |
Steroids (No) | 1.47 | [0.48–11.63] | 0.70 |
Steroids (Yes) | 0.84 | [0.10–2.08] | 0.67 |
Antimetabolites (No) | 0.42 | [0.06–0.91] | 0.95 |
Antimetabolites (Yes) | 1.92 | [1.00–10.16] | 0.89 |
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Cremoni, M.; Cuozzo, S.; Martinuzzi, E.; Barbosa, S.; Ben Hassen, N.; Massa, F.; Demonchy, E.; Durand, M.; Thaunat, O.; Esnault, V.; et al. Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients. Viruses 2022, 14, 542. https://doi.org/10.3390/v14030542
Cremoni M, Cuozzo S, Martinuzzi E, Barbosa S, Ben Hassen N, Massa F, Demonchy E, Durand M, Thaunat O, Esnault V, et al. Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients. Viruses. 2022; 14(3):542. https://doi.org/10.3390/v14030542
Chicago/Turabian StyleCremoni, Marion, Sébastien Cuozzo, Emanuela Martinuzzi, Susana Barbosa, Nadia Ben Hassen, Filippo Massa, Elisa Demonchy, Matthieu Durand, Olivier Thaunat, Vincent Esnault, and et al. 2022. "Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients" Viruses 14, no. 3: 542. https://doi.org/10.3390/v14030542
APA StyleCremoni, M., Cuozzo, S., Martinuzzi, E., Barbosa, S., Ben Hassen, N., Massa, F., Demonchy, E., Durand, M., Thaunat, O., Esnault, V., Le Quintrec, M., Caillard, S., Glaichenhaus, N., & Sicard, A. (2022). Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients. Viruses, 14(3), 542. https://doi.org/10.3390/v14030542