Clinical Characteristics, Treatments and Outcomes of 18 Lung Transplant Recipients with COVID-19
Abstract
:1. Introduction
2. Methods
2.1. Study Population, Setting, and Clinical Data
2.2. Laboratory and Radiology Assessment
2.3. Statistical Analysis
2.4. Ethical Consideration
3. Results
3.1. Clinical Patient Characteristics
3.2. Laboratory and Radiological Features
3.3. Therapeutic Intervention
3.4. Remdesivir in Patients with Impaired Renal Function
3.5. Autopsy in a Patient with COVID-19 with Siddiqi Stage III Disease
4. Discussion
4.1. COVID-19 Severity: The Siddiqi Stages
4.2. SARS-CoV-2 Infection: Extrapulmonary Manifestations
4.3. SARS-CoV-2 Infection: Pulmonary Manifestations
4.4. Liver Function Test Abnormalities
4.5. CRP as Marker of Disease Activity in COVID-19
4.6. COVID-19 and ABO Blood Group
4.7. AIFELL Score
4.8. Remdesivir in Patients with Impaired Renal Function
4.9. COVID-19 Convalescent Plasma (CCP)
4.10. Respiratory Co-Infections
4.11. Immunosuppressive Therapy during COVID-19
4.12. Hospital Admission Rate
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Limitation of Study
References
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Mild (Siddiqi I) n = 7 | Moderate (Siddiqi IIA,B) n = 9 | Severe (Siddiqi III) n = 2 | |
---|---|---|---|
Age, mean yrs., (range) | 41.3 (19–64) | 54.7 (28–68) | 58.5 (56–61) |
Male sex (%) | 3 (43%) | 7 (78%) | 2 (100%) |
BMI, mean (kg/m2) | 22.4 | 26.3 | 31.2 |
Pretransplant diagnosis | |||
Cystic fibrosis | 4 (57%) | 2 (22%) | 0 |
COPD | 1 (14%) | 4 (44%) | 0 |
ILD | 2 (29%) | 2 (22%) | 2 (100%) |
PAH | 0 | 1 (11%) | 0 |
Comorbidities (%) | |||
Hypertension | 2 (29%) | 6 (56%) | 2 (100%) |
Chronic kidney disease | 2 (29%) | 4 (44%) | 2 (100%) |
Diabetes | 2 (29%) | 3 (33%) | 1 (50%) |
Cardiovascular disease | 1 (14%) | 3 (33%) | 2 (100%) |
Malignancy | 0 | 4 (44%) | 1 (50%) |
Mild (Siddiqi I) n = 7 | Moderate (Siddiqi IIA,B) n = 9 | Severe (Siddiqi III) n = 2 | |
---|---|---|---|
Symptoms | |||
Fever | 2 (29%) | 7 (78%) | 0 |
Cough | 1 (14%) | 5 (56%) | 0 |
Dyspnea | 0 | 4 (44%) | 2 (100%) |
Sore throat | 0 | 0 | 0 |
Fatigue | 1 (14%) | 4 (44%) | 1 (50%) |
Anorexia | 1 (14%) | 2 (22%) | 0 |
Diarrhea | 1 (14%) | 2 (22%) | 0 |
Nausea/vomiting | 3 (43%) | 3 (33%) | 1 (50%) |
Altered sense of smell | 0 | 0 | 0 |
Altered sense of taste | 0 | 1 (11%) | 0 |
Headache | 2 (29%) | 3 (33%) | 0 |
Rhinorrhea | 1 (14%) | 1 (11%) | 0 |
Vital signs | |||
Temperature (°C) | 38.4 (37.9–38.8) | 37.3 (35.9–39.2) | 38.3 (36.8–39.8) |
Heart rate (bpm) | 118 | 82 (69–129) | 88 (81–95) |
Oxygen saturation, % | 96 | 96.4 (95–99) | 92 (90–93) |
Laboratory values, mean (range) | |||
CRP (mg/l) | 29.8 (4–77) | 58.2 (4.8–140) | 302 (199–406) |
Hemoglobin (g/l) | 135 (104–172) | 121 (96–152) | 113 (99–127) |
Thrombocytes (G/l) | 201 (153–313) | 186 (126–365) | 174 (172–176) |
Leucocytes (G/l) | 6.41 (3.67–10.6) | 6.67 (4.99–9.38) | 11.6 (5.9–17.3) |
Neutrophils (G/l) | 4.89 (3.26–8.03) | 5.29 (2.04–7.49) | 10.4 (4.1–16.1) |
Eosinophils (G/l) | 0.067 (0–0.14) | 0.024 (0–0.08) | 0 (0–0) |
Lymphocytes (G/l) | 0.95 (0.17–1.25) | 0.60 (0.18–1.58) | 1.29 (0.47–2.1) |
ASAT (U/l) | 42.7 (18–69) | 29.9 (14–44) | 44 (39–49) |
ALAT (U/l) | 47.3 (11–90) | 24.7 (12–39) | 16 (9–23) |
LDH (U/l) | 383 (309–450) | 486 (5–636) | 801 (500–1101) |
Bilirubin (µmol/l) | 17.7 (5–34) | 8.1 (4–15) | N/A |
Creatinine (µmol/l) | 119 (90–166) | 231 (17–809) | 208 (202–213) |
Creatinin kinase (U/l) | 46 (43–49) | 113 (25–525) | 92 (69–114) |
Blood Group (A, B, AB, 0) | |||
A (%) | 3 (43%) | 7 (78%) | 0 |
B (%) | 0 | 1 (11%) | 0 |
AB (%) | 0 | 0 | 0 |
0 (%) | 4 (57%) | 1 (11%) | 2 (100%) |
AIFELL Score at presentation | 1.5 (1–2) | 3.2 (2–4) | 4.5 (4–5) |
Mild (Siddiqi I) n = 7 | Moderate (Siddiqi IIA,B) n = 9 | Severe (Siddiqi III) n = 2 | |
---|---|---|---|
Immunosuppression | |||
Prednisone | 7 (100%) | 9 (100%) | 2 (100%) |
Mycophenolate mofetil | 6 (86%) | 7 (78%) | 2 (100%) |
Cyclosporine A | 1 (14%) | 3 (33%) | 2 (100%) |
Tacrolimus | 6 (86%) | 4 (44%) | 0 |
Everolimus | 0 | 1 (11%) | 0 |
Rapamycin | 1 (14%) | 0 | 0 |
Treatment | |||
Remdesivir | 0 | 6 (67%) | 0 |
Augmentin | 3 (43%) | 0 | 1 (50%) |
Ceftriaxone | 0 | 0 | 0 |
Tazobactam/piperacillin | 1 (14%) | 3 (33%) | 1 (50%) |
Meropenem | 0 | 3 (33%) | 1 (50%) |
Vancomycin | 0 | 1 (11%) | 0 |
Dexamethasone | 0 | 3 (33%) | 2 (100%) |
Treatment setting | |||
Ambulant | 6 (86%) | 0 | 0 |
Hospital, normal ward | 1 (14%) | 7 (78%) | 0 |
Hospital, intermediate care | 0 | 0 | 0 |
Hospital, intensive care | 0 | 2 (22%) | 2 (100%) |
Hospitalization (days) | 7 (7–7) | 22 (3–44) | 20 (19–20) |
Oxygenation | |||
Normal, room air | 7 (100%) | 5 (56%) | 0 |
Oxygen, nasal cannula | 0 | 3 (33%) | |
Oxygen, non-rebreather | 0 | 0 | 0 |
Oxygen, HFOT | 0 | 1 (11%) | 0 |
Non-invasive ventilation | 0 | 0 | 0 |
Mechanical ventilation | 0 | 0 | 2 (100%) |
ECMO | 0 | 0 | 0 |
Outcome | |||
Alive | 7 (100%) | 9 (100%) | 0 |
Dead | 0 | 0 | 2 (100%) |
Patient Number | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Date of COVID-19 | 10/ 2020 | 10/ 2020 | 03/ 2020 | 10/ 2020 | 10/ 2020 | 11/ 2020 | 11/ 2020 | 11/ 2020 | 12/ 2020 | 05/ 2020 | 11/ 2020 | 12/ 2020 | 01/ 2021 | 12/ 2020 | 01/ 2021 | 01/ 2021 | 01/ 2021 | 01/ 2021 |
Demographic | ||||||||||||||||||
Age (years) | 56 | 28 | 56 | 48 | 38 | 22 | 68 | 66 | 27 | 64 | 49 | 68 | 64 | 34 | 19 | 61 | 67 | 63 |
male/female | m | m | f | m | m | f | m | m | m | m | f | m | f | m | f | m | f | m |
BMI, kg/m2 | 31 | 27.4 | 21.9 | 19.3 | 19.6 | 20.3 | 42.8 | 27.1 | 19.5 | 27.7 | 18.9 | 22.4 | 27.4 | 14.9 | 15.2 | 31.4 | 37.5 | 31.8 |
Transplant Data | ||||||||||||||||||
Transplant year | 2019 | 2019 | 2019 | 2019 | 2006 | 2019 | 2015 | 2020 | 2014 | 2018 | 2016 | 2012 | 2016 | 2016 | 2020 | 2016 | 2010 | 2018 |
Previous disease | ILD | PAH | COPD | CF | CF | CF | COPD | IPF | CF | IPF | Pl.par.Fib | COPD | COPD | CF | CF | ILD | ILD | COPD |
Comorbidities | ||||||||||||||||||
Hypertension | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||
Diabetes | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||
Cardiovascular disease | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||
Malignancy | 1 | 1 | 1 | 1 | 1 | |||||||||||||
Chronic kidney disease | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||
Immunosuppression | ||||||||||||||||||
Prednison | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
MMF | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |||
Ciclosporine | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||
Tacrolimus | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||
Everolimus | 1 | |||||||||||||||||
Certican/rapamycin | 1 | |||||||||||||||||
Risk stratification | ||||||||||||||||||
Siddiqi Stage | III | IIA | I | IIB | IIB | I | IIA | IIA | I | I | IIA | IIB | IIB | I | I | III | I | IIA |
AIFELL Score | 4 | 1 | 2 | 4 | 3 | 3 | 4 | 2 | 4 | 4 | 1 | 5 | ||||||
Radiology | ||||||||||||||||||
Examination (CT/CXR) | CT | CT | CT | CT | CT | CT | CT | CT | CT | CT | CT | CXR | ||||||
GGO | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||
Consolidation | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||
Pleural Effusion | 1 | 1 | ||||||||||||||||
Pneumothorax | 1 | |||||||||||||||||
Treatment | ||||||||||||||||||
Antiviral | ||||||||||||||||||
Remdesivir | 1 | 1 HD dose | 1 | 1 HD dose | 1 | 1 | ||||||||||||
Antibiotics | ||||||||||||||||||
Azithromycin | ||||||||||||||||||
Augmentin | 1 | 1 | 1 | 1 | ||||||||||||||
Ceftriaxon | 1 | 1 | ||||||||||||||||
Tazobac | 1 | 1 | 1 | 1 | 1 | |||||||||||||
Meropenem | 1 | 1 | 1 | 1 | ||||||||||||||
Vancomycin | 1 | |||||||||||||||||
Corticosteroids | ||||||||||||||||||
Prednison | 1 | |||||||||||||||||
Dexamethasone | 1 | 1 | 1 | 1 | 1 | |||||||||||||
CCP | 1 | |||||||||||||||||
Treatment Setting | ||||||||||||||||||
Ambulant | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||
Hosp. normal ward | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||
Hosp. ICU | 1 | 1 | 1 | 1 | ||||||||||||||
No. of Hosp. Days | 20 | 3 | 7 | 43 | 44 | 9 | 26 | 3 | 36 | 7 | 19 | 23 | ||||||
Oxygenation | ||||||||||||||||||
Normal breathing no O2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Oxygen nasal cannula | 1 | 1 | 1 | |||||||||||||||
Oxygen HFOT | 1 | |||||||||||||||||
Mechanical ventilation | 1 | 1 | ||||||||||||||||
Outcome | ||||||||||||||||||
Alive | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||
Dead | 1 | 1 |
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Hage, R.; Steinack, C.; Gautschi, F.; Pfister, S.; Inci, I.; Schuurmans, M.M. Clinical Characteristics, Treatments and Outcomes of 18 Lung Transplant Recipients with COVID-19. Transplantology 2021, 2, 229-245. https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2020022
Hage R, Steinack C, Gautschi F, Pfister S, Inci I, Schuurmans MM. Clinical Characteristics, Treatments and Outcomes of 18 Lung Transplant Recipients with COVID-19. Transplantology. 2021; 2(2):229-245. https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2020022
Chicago/Turabian StyleHage, René, Carolin Steinack, Fiorenza Gautschi, Susan Pfister, Ilhan Inci, and Macé M. Schuurmans. 2021. "Clinical Characteristics, Treatments and Outcomes of 18 Lung Transplant Recipients with COVID-19" Transplantology 2, no. 2: 229-245. https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2020022