Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave
Abstract
:1. Introduction
2. Materials and Methods
2.1. Assessment of the Humoral and Cellular Spike-Specific Immune Response
2.2. Statistical Analysis
3. Results
3.1. Study Cohort and Patient Characteristics
3.2. The Clinical Course of Omicron Breakthrough Infections in Fully Vaccinated LTR
3.3. The Clinical Course of LTR Requiring Hospitalization for COVID-19 Complications
3.4. Range and Duration of Self-Reported Specific COVID-19 Symptoms after breakthrough infection
3.5. The Hybrid Cellular and Humoral Immune Response after Omicron Variant Breakthrough Infection in LTR
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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Characteristics 1 | LTR n = 98 n (%)/Median (IQR) | HC n = 19 n (%)/Median (IQR) |
---|---|---|
Age at the time of infection (years) | 56 (42–65) | 32 (25–47) |
Females | 46 (46.9) | 11 (57.9) |
BMI (kg/m2) | 24 (21.5–26.9) | - |
Time since transplantation (years) | 7 (3–13.3) | - |
Etiology of liver disease | ||
Alcoholic liver disease | 14 (14.3) | - |
Autoimmune | 25 (25.5) | - |
Viral | 15 (15.3) | - |
Hepatocellular carcinoma | 8 (8.2) | - |
Other | 36 (36.7) | - |
Risk factors | ||
Diabetes | 32 (32.7) | 0 |
Arterial Hypertension | 52 (53.1) | 2 (10.5) |
Age > 60 years | 37 (37.8) | 4 (21.1) |
eGFR < 30 mL/min | 18 (18.4) | - |
BMI > 30 kg/m2 | 13 (13.3) | 1 (5.3) |
2 Risk factors | 46 (46.9) | - |
≥3 Risk factors | 21 (21.4) | - |
Charlson comorbidity index | 5 (4–8) | - |
Vaccination status | ||
Second dose | 12 (12.2) | 0 |
Third dose | 59 (60.2) | 15 (78.9) |
Fourth dose | 25 (25.6) | 4 (21.1) |
Fifth dose | 2 (2) | 0 |
Time between last vaccine and infection (days) | 130 (88.8–183.3) (n = 86) | 139 (96.5–179) (n = 17) |
Immunosuppression | ||
Tacrolimus | 17 (17.3) | - |
Cyclosporine | 3 (3.1) | - |
mTORi | 2 (2) | - |
CNI + MMF | 24 (24.5) | - |
CNI + AZA | 3 (3.1) | - |
CNI + mTORi | 12 (12.3) | - |
CNI + prednisone | 16 (16.3) | - |
mTORi + MMF | 1 (1) | - |
mTORi + AZA | 0 | - |
mTORi + prednisone | 4 (4.1) | - |
≥3 Immunosuppressants | 16 (16.3) | - |
Laboratory values | ||
Leucocytes (Mrd/L) | 5.6 (4.1–7.3) (n = 84) | - |
Lymphocytes (Mrd/L) | 1.3 (0.8–2) (n = 77) | - |
eGFR (ml/min) | 62 (33.8–89.8) | - |
Management of SARS-CoV-2 infection | ||
Outpatient | 77 (78.6) | 19 (100) |
Non-COVID related hospitalization | 10 (10.2) | 0 |
COVID-related hospitalization | 11 (11.2) | 0 |
Characteristics 1 | LTR Not Requiring Hospitalization n = 87 n (%)/Median (IQR) | LTR Requiring Hospitalization n = 11 n (%)/Median (IQR) | p-Value |
---|---|---|---|
Age at the time of infection (years) | 54 (40–63) | 67 (65–71) | <0.001 |
Female | 41 (47.1) | 5 (45.5) | 0.818 |
BMI (kg/m²) | 23.7 (21.2–26.6) | 26.5 (24.9–31.1) | 0.004 |
Time since transplantation (years) | 7 (3–13) | 11 (1–14) | 0.831 |
Risk factors | |||
Diabetes | 24 (27.6) | 8 (72.7) | 0.008 |
Arterial hypertension | 42 (48.3) | 10 (90.9) | 0.008 |
Age > 60 years | 27 (31) | 10 (90.9) | <0.001 |
eGFR < 30 mL/min | 13 (14.9) | 5 (45.5) | 0.027 |
BMI > 30 kg/m² | 9 (10.3) | 4 (36.4) | 0.037 |
2 Risk factors | 36 (41.4) | 10 (90.9) | 0.002 |
≥3 Risk factors | 11 (12.6) | 10 (90.9) | <0.001 |
Charlson comorbidity index | 5 (4–7) | 9 (7–14) | <0.001 |
Vaccination status | |||
Second dose | 11 (12.6) | 1 (9.1) | 1.0 |
Third dose | 56 (64.4) | 3 (27.3) | 0.024 |
Fourth dose | 19 (21.8) | 6 (54.5) | 0.029 |
Fifth dose | 1 (1.1) | 1 (9.1) | 0.213 |
Homologous mRNA-based vaccination | 72 (85.7) (n = 84) | 9 (90) (n = 10) | 1.0 |
Heterologous mRNA/vector-based vaccination | 12 (14.3) (n = 84) | 1 (10) (n = 10) | 1.0 |
Anti-S RBD antibody titer pre-infection | |||
Median anti-S RBD (AU/mL) | 2044 (n = 43) | 508.3 (n = 11) | 0.03 |
Anti-S RBD < 103 AU/mL | 19 (44.2) (n = 43) | 8 (72.7) (n = 11) | 0.175 |
Immunosuppression | |||
Monotherapy | 20 (23) | 2 (18.2) | 1.0 |
CNI + MMF /mTORi/Prednisone/AZA | 49 (56.3) | 6 (54.5) | 0.911 |
mTORi + MMF/Prednisone/AZA | 3 (3.4) | 2 (18.2) | 0.095 |
Additional MMF medication | 28 (32.2) | 4 (36.4) | 0.746 |
≥3 Immunosuppressants | 15 (17.2) | 1 (9.1) | 0.686 |
COVID-19 therapy | |||
Antiviral | 6 (6.9) | 3 (27.3) | - |
Antibody | 2 (2.3) | 3 (27.3) | - |
Combination of both | 5 (5.7) | 0 | - |
Dexamethasone | - | 4 (36.4) | - |
Reduction of Immunosuppressants | - | 5 (45.5) | - |
Laboratory values | |||
Leucocytes (Mrd/L) | 5.8 (4.1–7.3) (n = 73) | 4.6 (3.5–6.9) (n = 11) | 0.195 |
Lymphocytes (Mrd/L) | 1.5 (0.8–2) (n = 66) | 0.9 (0.8–1.4) (n = 11) | 0.238 |
eGFR (ml/min) | 65 (36–93) | 32 (18–50) | 0.015 |
Characteristics 1 | LTR with Long-Lasting Symptoms n = 30 n (%)/Median (IQR) | LTR without Long-Lasting Symptoms n = 50 n (%)/Median (IQR) | p-Value |
---|---|---|---|
Age at the time of infection (years) | 57 (39.5–65.5) | 54.5 (42.8–65.3) | 0.876 |
Female | 17 (56.7) | 17 (34) | 0.047 |
BMI (kg/m²) | 24.1 (21.4–28.1) | 23.8 (21.1–26.6) | 0.522 |
Time since transplantation (years) | 5.5 (2.8–11) | 7 (3–14) | 0.551 |
Risk factors | |||
Diabetes | 10 (33.3) | 15 (30) | 0.755 |
Arterial hypertension | 14 (46.7) | 27 (54) | 0.525 |
Age > 60 years | 13 (43.3) | 16 (32) | 0.307 |
eGFR < 30 mL/min | 4 (13.3) | 10 (20) | 0.447 |
BMI > 30 kg/m2 | 5 (16.7) | 4 (8) | 0.284 |
2 Risk factors | 14 (46.7) | 23 (46) | 0.954 |
≥3 Risk factors | 5 (16.7) | 9 (18) | 0.879 |
Charlson comorbidity index | 5 (4–7.3) | 5 (4–8) | 0.946 |
Vaccination status | |||
Second dose | 2 (16.7) | 7 (14) | 0.471 |
Third dose | 18 (60) | 34 (68) | 0.468 |
Fourth dose | 9 (30) | 8 (16) | 0.138 |
Fifth dose | 1 (3.3) | 1 (2) | 1.0 |
Immunosuppression | |||
Monotherapy | 8 (26.7) | 8 (16) | 0.248 |
CNI + MMF /mTORi/Prednisone/AZA | 18 (60) | 31 (62) | 0.859 |
mTORi + MMF /Prednisone/AZA | 1 (3.3) | 2 (4) | 1.0 |
≥3 Immunosuppressants | 3 (10) | 9 (18) | 0.52 |
Additional MMF medication | 9 (30) | 19 (38) | 0.468 |
Humoral immune response | |||
Anti-S RBD prior to infection (AU/mL) | 3666 (388.6–15,185) (n = 17) | 1715 (11.6–5441) (n = 24) | 0.058 |
Anti-S RBD post-infection (AU/mL) | 19,868 (13,122–72,390) (n = 19) | 22,016 (6110–63,960) (n = 33) | 0.665 |
Symptoms of acute COVID-19 | |||
Fever | 14 (53.3) | 16 (33.3) | 0.239 |
Myalgia/arthralgia | 13 (43.3) | 15 (31.3) | 0.279 |
Fatigue | 22 (73.3) | 28 (58.3) | 0.179 |
Cough | 17 (56.7) | 26 (54.2) | 0.829 |
Rhinorrhea | 18 (60) | 26 (54.2) | 0.613 |
Sore throat | 20 (66.7) | 22 (45.8) | 0.073 |
Headache | 15 (50) | 17 (37) | 0.26 |
Nausea | 4 (13.3) | 3 (6.3) | 0.287 |
Diarrhea | 5 (16.7) | 7 (14.6) | 1.0 |
Dyspnea | 12 (40) | 6 (12.5) | 0.005 |
Loss of smell/taste | 5 (16.7) | 3 (6.4) | 0.25 |
Difficulty concentrating | 12 (40) | 7 (14.6) | 0.011 |
COVID-19 disease course | |||
SARS-CoV-2 positivity < 30 days | 4 (13.3) | 3 (6) | 0.416 |
Hospitalization for COVID-19 required | 4 (13.3) | 3 (6) | 0.416 |
Laboratory values | |||
Leucocytes (Mrd/L) | 5.8 (3.9–7.3) (n = 26) | 5.4 (3.9–7.2)(n = 41) | 0.607 |
Lymphocytes (Mrd/L) | 1.5 (0.9–1.8) (n = 26) | 1.3 (0.7–2) (n = 34) | 0.493 |
eGFR (ml/min) | 62.5 (38.3–92.3) | 60.5 (31.8–90) | 0.702 |
Regression Coefficient | p-Value | Odds Ratio | 95% Confidence Interval | |
---|---|---|---|---|
Female sex | 1.593 | 0.01 | 4.917 | 1.469–16.461 |
Age (years) | 0.011 | 0.651 | 1.011 | 0.963–1.062 |
Charlson comorbidity index | −0.036 | 0.799 | 0.965 | 0.733–1.270 |
≥3 immunosuppressants | −1.419 | 0.085 | 0.242 | 0.048–1.213 |
Difficulty concentrating | 0.553 | 0.429 | 1.738 | 0.441–6.852 |
Dyspnea | 1.977 | 0.009 | 7.224 | 1.649–31.644 |
≥3 vaccine doses | 1.079 | 0.085 | 2.942 | 0.842–10.278 |
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Herting, A.; Jahnke-Triankowski, J.; Harberts, A.; Schaub, G.M.; Lütgehetmann, M.; Ruether, D.F.; Fischer, L.; Addo, M.M.; Lohse, A.W.; Schulze zur Wiesch, J.; et al. Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave. Viruses 2023, 15, 297. https://doi.org/10.3390/v15020297
Herting A, Jahnke-Triankowski J, Harberts A, Schaub GM, Lütgehetmann M, Ruether DF, Fischer L, Addo MM, Lohse AW, Schulze zur Wiesch J, et al. Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave. Viruses. 2023; 15(2):297. https://doi.org/10.3390/v15020297
Chicago/Turabian StyleHerting, Anna, Jacqueline Jahnke-Triankowski, Aenne Harberts, Golda M. Schaub, Marc Lütgehetmann, Darius F. Ruether, Lutz Fischer, Marylyn M. Addo, Ansgar W. Lohse, Julian Schulze zur Wiesch, and et al. 2023. "Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave" Viruses 15, no. 2: 297. https://doi.org/10.3390/v15020297
APA StyleHerting, A., Jahnke-Triankowski, J., Harberts, A., Schaub, G. M., Lütgehetmann, M., Ruether, D. F., Fischer, L., Addo, M. M., Lohse, A. W., Schulze zur Wiesch, J., & Sterneck, M. (2023). Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave. Viruses, 15(2), 297. https://doi.org/10.3390/v15020297