Severe COVID-19 Illness and α1-Antitrypsin Deficiency: COVID-AATD Study
Abstract
:1. Introduction
2. Materials and Methods
Statistical Analysis
3. Results
3.1. Characteristics of the Study Population
3.2. Characteristics According to the Presence of Genetic Mutations Associated with AATD
3.3. Characteristics According to A1AT Levels
3.4. Characteristics According to COVID-19 Severity
3.5. Factors Related to COVID-19 Severity
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Enrolled Patients | n = 2022 |
---|---|
Age, years, median (IQR) | 61.2 (51–71) |
Gender (male), n % | 59.9 |
| |
Current smoker | 5.9 |
Former smoker | 39.7 |
Never smoked | 54.4 |
| 25 (12–40) |
Body mass index, kg/m2, median (IQR) | 29.2 (26.1–33) |
Pulmonary comorbidity, n (%) | 427 (21.1) |
| 122 (6) |
| 186 (9.2) |
| 151 (7.5) |
| 23 (1.1) |
Home oxygen therapy, n (%) | 25 (1.2) |
Comorbidities | |
| 385 (19.1) |
| 795 (39.4) |
| 677 (33.5) |
| 226 (11.2) |
| 90 (4.5) |
| 80 (4) |
| 63 (3.1) |
| 147 (7.3) |
Bilateral pneumonia, n (%) | 1533 (76.3) |
Inpatient, n (%) | 1592 (78.8) |
Hospitalization day, median (IQR) | 9 (3–17) |
ICU/UCIR, n (%) | 507 (25.1) |
High flow oxygen or NIV/CPAP, n (%) | 872 (43.2) |
Deaths, n (%) | 6 (0.3) |
A1AT mg/dL, median (IQR) | 129 (116–148) |
| 74 |
| 25.6 |
| 0.4 |
CRP level, m (SD) | 0.90 (0.29–4.42) |
Genotyping Test, n (%) | |
| 1551 (79.3) |
| 6 (0.3) |
| 318 (16.3) |
| 41 (2.1) |
| 2 (0.1) |
| 5 (0.3) |
| 1 (0.1) |
| 22 (1.1) |
| 5 (0.3) |
| 4 (0.2) |
Enrolled Patients with Genotyping Test n = 1955 | Absence Mutations n = 1551 (79.3%) | Presence Mutations n = 404 (20.7%) | p |
---|---|---|---|
Age, years, m (SD) | 60 (13.9) | 61.8 (14.1) | 0.021 |
Gender (male), n % | 921 (59.4) | 255 (63.1) | 0.176 |
| |||
Current smoker | 82 (5.3) | 32 (7.9) | 0.044 |
Former smoker | 596 (38.7) | 173 (43.3) | 0.099 |
| 22.7 (10–40) | 25 (15–40) | 0.039 |
Body mass index, kg/m2, median (IQR) | 29.2 (26.1–33) | 29.39 (26–33.3) | 0.618 |
| 333 (21.5) | 84 (20.8) | 0.785 |
COPD, n (%) | 91 (5.9) | 27 (6.7) | 0.534 |
Asthma, n (%) | 144 (9.3) | 35 (8.7) | 0.702 |
ILD, n (%) | 17 (1.1) | 4 (1) | 1.000 |
Home oxygen therapy, n (%) | 16 (1) | 9 (2.2) | 0.056 |
| |||
Diabetes mellitus | 291 (18.8) | 84 (20.9) | 0.333 |
Hypertension | 611 (39.4) | 165 (40.9) | 0.578 |
Dyslipemia | 495 (32) | 159 (39.5) | 0.005 |
Coronary artery disease | 179 (11.6) | 45 (11.2) | 0.839 |
Nephropatia | 69 (4.5) | 19 (4.7) | 0.789 |
Hepatopathy | 66 (4.3) | 14 (3.5) | 0.461 |
Immunosuppression | 41 (2.6) | 18 (4.5) | 0.057 |
History of cancer | 105 (6.8) | 36 (8.9) | 0.136 |
Bilateral pneumonia, n (%) | 1165 (75.6) | 328 (81.8) | 0.009 |
Inpatient, n (%) | 1211 (78,1) | 342 (84,9) | 0.003 |
Hospitalization day, m (SD) | 8 (3–16) | 11 (4–20) | <0.001 |
ICU/UCIR, n (%) | 368 (23.7) | 120 (29.8) | 0.013 |
High flow oxygen or NIV/CPAP, n (%) | 649 (41.9) | 193 (48) | 0.028 |
Severe COVID-19, n (%) | 656 (42.4) | 196 (48.8) | 0.022 |
Deaths, n (%) | 4 (0.3) | 2 (0.5) | 0.610 |
A1AT mg/dL, m (SD) | 138.8 (25.8) | 106.3 (24) | <0.001 |
| 1153 (86.2) | 91 (26.6) | <0.001 |
| 184 (13.8) | 251 (73.4) |
Enrolled Patients with A1AT Level n = 1691 | A1AT ≥ 116 mg/dL n = 1251 (74%) | A1AT < 116 mg/dL n = 440 (26%) | p |
---|---|---|---|
Age, years, m (SD) | 61 (14) | 60.2 (13.2) | 0.288 |
Gender (male), n % | 744 (59.5) | 279 (63.4) | 0.151 |
| |||
Current smoker | 62 (5) | 33 (7.5) | 0.047 |
Former smoker | 488 (39.2) | 185 (42) | 0.289 |
| 25 (11.4–40) | 25 (15–40) | 0.464 |
Body mass index, kg/m2, median (IQR) | 29.3 (26.2–33.2) | 29.6 (26.2–33.2) | 0.455 |
Pulmonary comorbidity, n (%) | 268 (21.4) | 91 (20.7) | 0.744 |
| 78 (6.2) | 30 (6.8) | 0.670 |
| 117 (9.4) | 35 (8) | 0.380 |
| 10 (0.8) | 6 (1.4) | 0.389 |
Home oxygen therapy, n (%) | 15 (1.2) | 10 (2.3) | 0.109 |
Comorbidities, n (%) | |||
| 251 (20.1) | 85 (19.3) | 0.731 |
| 535 (42.8) | 158 (35.9) | 0.011 |
| 435 (34.9) | 160 (36.4) | 0.569 |
| 159 (12.7) | 38 (8.7) | 0.022 |
| 56 (4.5) | 16 (3.6) | 0.449 |
| 55 (4.1) | 17 (3.9) | 0.622 |
| 28 (2.2) | 12 (2.7) | 0.561 |
| 91 (7.3) | 27 (6.1) | 0.418 |
Bilateral pneumonia, n (%) | 926 (74.4) | 362 (83) | <0.001 |
Inpatient, n (%) | 973 (77.8) | 372 (84.5) | 0.003 |
Hospitalization day, m (SD) | 8 (3–16.2) | 11 (5–19.7) | <0.001 |
ICU/UCIR, n (%) | 296 (23.7) | 135 (30.7) | 0.004 |
High flow oxygen or NIV/CPAP, n (%) | 539 (43.2) | 224 (51) | 0.005 |
Deaths, n (%) | 4 (0.3) | 2 (0.5) | 0.654 |
Genotyping Test, n (%) | |||
| 1153 (92.7) | 184 (42.3) | |
| 2 (0.2) | 4 (0.9) | |
| 87 (7) | 78 (40.9) | |
| 0 | 37 (8.5) | |
| 0 | 2 (0.5) | |
| 2 (0.2) | 3 (0.7) | |
| 0 | 1 (0.2) | |
| 0 | 18 (4.1) | |
| 0 | 4 (0.9) | |
| 0 | 4 (0.9) | |
A1AT mg/dL, m (SD) | 143.4 (23.6) | 99.8 (13.8) | <0.001 |
CRP_nivel, m (SD) | 0.95 (0.29–5) | 1 (0.20–6.25) | 0.436 |
n = 2217 | Non-Severe COVID-19 n = 1145 (56.8) | Severe COVID-19 n = 872 (43.2) | p-Value |
---|---|---|---|
Age, years, m (SD) | 58.9 (14.7) | 62.2 (12.8) | <0.001 |
Gender (male), n % | 54.3 | 67.4 | <0.001 |
Smoking status, n (%) | |||
| 83 (7.3) | 37 (4.3) | 0.005 |
| 393 (34.7) | 400 (46.1) | <0.001 |
IPA, median (IQR) | 20 (10–40) | 25 (15-40) | <0.001 |
Body mass index, kg/m2, m (SD) | 29 (25.7–33.3) | 29.4 (26.7–32.6) | 0.140 |
Pulmonary comorbidity, n (%) | 243 (21.2) | 183 (21) | 0.897 |
| 65 (5.7) | 57 (6.5) | 0.418 |
| 117 (10.2) | 69 (7.9) | 0.076 |
| 13 (1.1) | 10 (1.2) | 0.978 |
Home oxygen therapy, n (%) | 9 (0.8) | 15 (1.7) | 0.055 |
| |||
Diabetes_mellitus | 174 (15.2) | 210 (24.1) | <0.001 |
Hypertension | 402 (35.1) | 391 (44.8) | <0.001 |
Dyslipemia | 301 (26.3) | 374 (42.9) | <0.001 |
Coronary artery disease | 98 (8.6) | 127 (14.6) | <0.001 |
Nephropathy | 45 (3.9) | 45 (5.2) | 0.188 |
Hepatopathy | 39 (3.4) | 41 (4.8) | 0.135 |
Immunosuppression | 34 (3) | 29 (3.3) | 0.649 |
History of cancer | 72 (6.3) | 75 (8.6) | 0.048 |
AAT mg/dL, m (SD) | 131.9 (31.1) | 132.2 (26.6) | |
| 704 (76.9) | 544 (70.5) | 0.859 |
| 209 (22.8) | 223 (28.9) | 0.006 |
| 2 (0.2) | 5 (0.6) | |
A1AT mg/dL, % | 0.003 | ||
| 704 (76.9) | 544 (70.5) | |
| 211 (18.4) | 228 (29.5) | |
A1AT genotyping test, n (%) | 0.022 | ||
| 892 (81.2) | 656 (77) | |
| 206 (18.8) | 196 (23) | |
MI, n (%) | 3 (0.3) | 3 (0.4) | |
MS, n (%) | 166 (15.1) | 150 (17.6) | |
MZ, n (%) | 14 (1.3) | 27 (3.2) | |
MM malton | 2 (0.2) | 0 | |
MP lowell | 4 (0.4) | 1 (0.1) | |
MM procida | 1 (0.1) | 0 | |
SS | 13 (1.2) | 9 (1.1) | |
SZ | 2 (0.2) | 3 (0.4) | |
ZZ | 1 (0.1) | 3 (0.4) |
OR (95% CI) | p-Value | |
---|---|---|
Age | 1.017 (1.011–1.024) | <0.001 |
Gender (female) | 0.573 (0.477–0.689) | <0.001 |
Diabetes_mellitus | 1.773 (1.417–2.218) | <0.001 |
Hypertension | 1.500 (1.253–1.797) | <0.001 |
Dyslipemia | 2.105 (1.744–2.540) | <0.001 |
Coronary artery disease | 1.820 (1.376–2.408) | <0.001 |
History of cancer | 1.401 (1.001–1.961) | 0.049 |
Current smoker | 0.568 (0.381–0.846) | 0.005 |
Former smoker | 1.611 (1.344–1.930) | <0.001 |
A1AT level < 116 mg/dL | 1.398 (1.124–1.739) | 0.003 |
Presence mutations | 1.294 (1.038–1.612) | 0.022 |
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Rodríguez Hermosa, J.L.; Vargas Centanaro, G.; González Castro, M.E.; Miravitlles, M.; Lázaro-Asegurado, L.; Jiménez-Rodríguez, B.M.; Rodríguez, R.A.; Moreno Méndez, R.; Torres-Duran, M.; Hernández-Pérez, J.M.; et al. Severe COVID-19 Illness and α1-Antitrypsin Deficiency: COVID-AATD Study. Biomedicines 2023, 11, 516. https://doi.org/10.3390/biomedicines11020516
Rodríguez Hermosa JL, Vargas Centanaro G, González Castro ME, Miravitlles M, Lázaro-Asegurado L, Jiménez-Rodríguez BM, Rodríguez RA, Moreno Méndez R, Torres-Duran M, Hernández-Pérez JM, et al. Severe COVID-19 Illness and α1-Antitrypsin Deficiency: COVID-AATD Study. Biomedicines. 2023; 11(2):516. https://doi.org/10.3390/biomedicines11020516
Chicago/Turabian StyleRodríguez Hermosa, Juan Luis, Gianna Vargas Centanaro, María Estela González Castro, Marc Miravitlles, Lourdes Lázaro-Asegurado, Beatriz María Jiménez-Rodríguez, Rosanel Amaro Rodríguez, Rosaly Moreno Méndez, María Torres-Duran, José María Hernández-Pérez, and et al. 2023. "Severe COVID-19 Illness and α1-Antitrypsin Deficiency: COVID-AATD Study" Biomedicines 11, no. 2: 516. https://doi.org/10.3390/biomedicines11020516
APA StyleRodríguez Hermosa, J. L., Vargas Centanaro, G., González Castro, M. E., Miravitlles, M., Lázaro-Asegurado, L., Jiménez-Rodríguez, B. M., Rodríguez, R. A., Moreno Méndez, R., Torres-Duran, M., Hernández-Pérez, J. M., Humanes-Navarro, A. M., & Calle Rubio, M. (2023). Severe COVID-19 Illness and α1-Antitrypsin Deficiency: COVID-AATD Study. Biomedicines, 11(2), 516. https://doi.org/10.3390/biomedicines11020516