HLA Allele Frequencies and Association with Severity of COVID-19 Infection in Northern Italian Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. HLA—Class I and II Genotyping
2.3. Statistical Analysis
3. Results
3.1. HLA Allelic Distribution in Patients with Different COVID-19 Severity
3.2. HLA Distribution Profiles of COVID-19 Patients
3.3. Multinomial Regression Analysis of HLA Association Accounted for Comorbidities
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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Disease | Mild (36) | Moderate (20) | Severe (40) | Total (96) | p Value | ||||
---|---|---|---|---|---|---|---|---|---|
Mean Age (ds) | 50.1 | (9.6) | 65.7 | (15.4) | 65.8 | (9.62) | 59.9 | (13.3) | <0.001 |
Gender Male n% | 14 | 38.9% | 11 | 55.0% | 28 | 70.0% | 53 | 55.2% | 0.025 |
Hypertension n% | 5 | 13.9% | 11 | 55.0% | 28 | 70.0% | 44 | 45.8% | <0.001 |
Active Smoking n% | 7 | 19.4% | 3 | 15.0% | 12 | 30.0% | 22 | 22.9% | 0.35 |
Obstructive Sleep Apnea Syndrome (OSAS) n% | 1 | 2.8% | 2 | 10.0% | 13 | 32.5% | 16 | 16.7% | 0.002 |
Diabetes Mellitus n% | 0 | 0.0% | 4 | 20.0% | 8 | 20.0% | 12 | 12.5% | 0.02 |
Ischemic Heart Disease n% | 2 | 8.3% | 5 | 25.0% | 6 | 15.0% | 13 | 13.5% | 0.12 |
Chronic Obstructive Pulmonary Disease n% | 0 | 0.0% | 3 | 15.0% | 4 | 10.0% | 7 | 7.3% | 0.08 |
Malignancy n% | 1 | 2.8% | 2 | 10.0% | 5 | 12.5% | 8 | 8.3% | 0.29 |
Asthma n% | 4 | 11.1% | 1 | 5.0% | 1 | 2.5% | 6 | 6.2% | 0.29 |
Supertype | Locus B | Mild (72) | Moderate (40) | Severe (80) | Total (192) | ||||
---|---|---|---|---|---|---|---|---|---|
n | % | n | % | n | % | n | % | ||
B07 | 07:02 | 3 | 4.4 | 5 | 13.2 | 3 | 3.8 | 11 | 5.9 |
B07 | 07:05 | 0 | 0.0 | 0 | 0.0 | 1 | 1.3 | 1 | 0.5 |
UND | 07:10 | 0 | 0.0 | 0 | 0.0 | 1 | 1.3 | 1 | 0.5 |
B08 | 08:01 | 3 | 4.4 | 5 | 13.2 | 2 | 2.5 | 10 | 5.4 |
B62 | 13:02 | 4 | 5.9 | 3 | 7.9 | 3 | 3.8 | 10 | 5.4 |
B27 | 14:02 | 5 | 7.4 | 0 | 0.0 | 5 | 6.3 | 10 | 5.4 |
B62 | 15:01 | 0 | 0.0 | 1 | 2.6 | 2 | 2.5 | 3 | 1.6 |
B27 | 15:03 | 1 | 1.5 | 0 | 0.0 | 0 | 0.0 | 1 | 0.5 |
B62 | 15:04 | 0 | 0.0 | 0 | 0.0 | 1 | 1.3 | 1 | 0.5 |
B58 | 15:17 | 0 | 0.0 | 0 | 0.0 | 1 | 1.3 | 1 | 0.5 |
B62 | 15:39 | 1 | 1.5 | 0 | 0.0 | 0 | 0.0 | 1 | 0.5 |
B44 | 18:01 | 12 | 17.6 | 4 | 10.5 | 7 | 8.8 | 23 | 12.4 |
UND | 18:18 | 0 | 0.0 | 1 | 2.6 | 0 | 0.0 | 1 | 0.5 |
B27 | 27:01 | 2 | 2.9 | 0 | 0.0 | 0 | 0.0 | 2 | 1.1 |
B27 | 27:02 | 1 | 1.5 | 0 | 0.0 | 0 | 0.0 | 1 | 0.5 |
B27 | 27:03 | 1 | 1.5 | 0 | 0.0 | 0 | 0.0 | 1 | 0.5 |
B07 | 35:01 | 4 | 5.9 | 2 | 5.3 | 13 | 16.3 | 19 | 10.2 |
B07 | 35:02 | 3 | 4.4 | 2 | 5.3 | 2 | 2.5 | 7 | 3.8 |
B07 | 35:03 | 0 | 0.0 | 1 | 2.6 | 1 | 1.3 | 2 | 1.1 |
B07 | 35:08 | 0 | 0.0 | 2 | 5.3 | 0 | 0.0 | 2 | 1.1 |
B07 | 35:09 | 0 | 0.0 | 0 | 0.0 | 1 | 1.3 | 1 | 0.5 |
B44 | 37:01 | 1 | 1.5 | 1 | 2.6 | 0 | 0.0 | 2 | 1.1 |
B27 | 38:01 | 5 | 7.4 | 1 | 2.6 | 3 | 3.8 | 9 | 4.8 |
B27 | 39:01 | 5 | 7.4 | 0 | 0.0 | 2 | 2.5 | 7 | 3.8 |
B44 | 40:01 | 2 | 2.9 | 0 | 0.0 | 1 | 1.3 | 3 | 1.6 |
B44 | 40:02 | 0 | 0.0 | 0 | 0.0 | 2 | 2.5 | 2 | 1.1 |
B44 | 41:01 | 0 | 0.0 | 2 | 5.3 | 0 | 0.0 | 2 | 1.1 |
B44 | 44:02 | 4 | 5.9 | 2 | 5.3 | 5 | 6.3 | 11 | 5.9 |
B44 | 44:03 | 2 | 2.9 | 1 | 2.6 | 0 | 0.0 | 3 | 1.6 |
B44 | 44:05 | 0 | 0.0 | 0 | 0.0 | 3 | 3.8 | 3 | 1.6 |
B44 | 45:01 | 1 | 1.5 | 0 | 0.0 | 0 | 0.0 | 1 | 0.5 |
UND | 47:01 | 0 | 0.0 | 1 | 2.6 | 0 | 0.0 | 1 | 0.5 |
B44 | 49:01 | 2 | 2.9 | 0 | 0.0 | 1 | 1.3 | 3 | 1.6 |
B44 | 50:01 | 1 | 1.5 | 0 | 0.0 | 0 | 0.0 | 1 | 0.5 |
B07 | 51:01 | 3 * | 4.4 | 3 | 7.9 | 12 * | 15.0 | 18 | 9.7 |
B62 | 52:01 | 4 | 5.9 | 1 | 2.6 | 0 | 0.0 | 5 | 2.7 |
B07 | 53:01 | 1 | 1.5 | 1 | 2.6 | 2 | 2.5 | 4 | 2.2 |
B07 | 55:01 | 1 | 1.5 | 0 | 0.0 | 2 | 2.5 | 3 | 1.6 |
B58 | 57:02 | 0 | 0.0 | 1 | 2.6 | 0 | 0.0 | 1 | 0.5 |
B58 | 58:01 | 0 | 0.0 | 0 | 0.0 | 3 | 3.8 | 3 | 1.6 |
B27 | 73:01 | 0 | 0.0 | 0 | 0.0 | 1 | 1.3 | 1 | 0.5 |
pc = 0.02, df = 80 |
Locus B | Mild (72) | Moderate (40) | Severe (80) | Total (192) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Supertype | n | % | n | % | n | % | n | % | p Value | OR | 95% CI |
B07 | *° 15 | 20.8 | °16 | 40.0 | * 37 | 46.3 | 68 | 15 | * pf = 0.002 * p = 0.01, df = 6 ° pf = 0.05 pc = 0.30, df = 6 | * 3.2 ° 2.5 | * 1.6–6.8 ° 1.1–5.9 |
B08 | 3 | 4.2 | 5 | 12.5 | 2 | 2.5 | 10 | 3 | ns | ||
B27 | *° 20 | 27.8 | ° 1 | 2.5 | * 11 | 13.8 | 32 | 20 | * pf = 0.05 * pc = 0.30, df = 6 ° pf = 0.001 pc = 0.006, df = 6 | * 0.4 ° 0.06 | * 0.2–0.9 ° 0–0.4 |
B44 | 25 | 34.7 | 10 | 25.0 | 19 | 23.8 | 54 | 25 | ns | ||
B58 | 0 | 0.0 | 1 | 2.5 | 4 | 5.0 | 5 | 0 | ns | ||
B62 | 5 | 6.9 | 2 | 5.0 | 3 | 3.8 | 10 | 5 | ns | ||
UND | 4 | 5.6 | 5 | 12.5 | 4 | 5.0 | 13 | 4 | ns | ||
pc = 0.001, df = 12 |
Locus C | Mild (72) | Moderate (40) | Severe (80) | Total (192) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
n | % | n | % | n | % | n | % | p Value | OR | 95% CI | |
01:02 | 3 | 4.2 | 1 | 2.5 | 7 | 8.8 | 11 | 5.7 | ns | ||
02:02 | 2 | 2.8 | 2 | 5.0 | 5 | 6.3 | 9 | 4.7 | ns | ||
02:10 | 1 | 1.4 | 0 | 0.0 | 0 | 0.0 | 1 | 0.5 | ns | ||
03:02 | 0 | 0.0 | 1 | 2.5 | 2 | 2.5 | 3 | 1.6 | ns | ||
03.03 | 0 | 0.0 | 0 | 0.0 | 1 | 1.3 | 1 | 0.5 | ns | ||
03:04 | 3 | 4.2 | 0 | 0.0 | 1 | 1.3 | 4 | 2.1 | ns | ||
04:01 | 10 | 13.9 | 8 | 20.0 | 19 | 23.8 | 37 | 19.3 | ns | ||
05:01 | 6 | 8.3 | 3 | 7.5 | 6 | 7.5 | 15 | 7.8 | ns | ||
06:02 | 7 | 9.7 | 4 | 10.0 | 3 | 3.8 | 14 | 7.3 | ns | ||
07:01 | 8 | 11.1 | 6 | 15.0 | 8 | 10.0 | 22 | 11.5 | ns | ||
07:02 | 4 | 5.6 | 7 | 17.5 | 5 | 6.3 | 16 | 8.3 | ns | ||
07:18 | 0 | 0.0 | 1 | 2.5 | 1 | 1.3 | 2 | 1.0 | ns | ||
08:01 | 3 | 4.2 | 0 | 0.0 | 2 | 2.5 | 5 | 2.6 | ns | ||
08:02 | 0 | 0.0 | 0 | 0.0 | 4 | 5.0 | 4 | 2.1 | ns | ||
12:02 | *° 16 | 22.2 | ° 1 | 2.5 | * 0 | 0.0 | 17 | 8.9 | * pf < 0.001 * pc < 0.001, df = 19 ° pf = 0.006 ° pc = 0.10, df = 17 | * 0 ° 0 | * 0–0.15 ° 0–0.5 |
12:03 | 2 | 2.8 | 2 | 5.0 | 7 | 8.8 | 11 | 5.7 | ns | ||
14:02 | 1 | 1.4 | 1 | 2.5 | 1 | 1.3 | 3 | 1.6 | ns | ||
15:02 | 2 | 2.8 | 0 | 0.0 | 5 | 6.3 | 7 | 3.6 | ns | ||
15:05 | 0 | 0.0 | 0 | 0.0 | 2 | 2.5 | 2 | 1.0 | ns | ||
16:01 | 4 | 5.6 | 1 | 2.5 | 1 | 1.3 | 6 | 3.1 | ns | ||
17:01 | 0 | 0.0 | 2 | 5.0 | 0 | 0 | 2 | 1.0 | ns | ||
pc = 0.002, df = 40 |
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Guerini, F.R.; Bolognesi, E.; Lax, A.; Bianchi, L.N.C.; Caronni, A.; Zanzottera, M.; Agliardi, C.; Albergoni, M.P.; Banfi, P.I.; Navarro, J.; et al. HLA Allele Frequencies and Association with Severity of COVID-19 Infection in Northern Italian Patients. Cells 2022, 11, 1792. https://doi.org/10.3390/cells11111792
Guerini FR, Bolognesi E, Lax A, Bianchi LNC, Caronni A, Zanzottera M, Agliardi C, Albergoni MP, Banfi PI, Navarro J, et al. HLA Allele Frequencies and Association with Severity of COVID-19 Infection in Northern Italian Patients. Cells. 2022; 11(11):1792. https://doi.org/10.3390/cells11111792
Chicago/Turabian StyleGuerini, Franca Rosa, Elisabetta Bolognesi, Agata Lax, Luca Nicola Cesare Bianchi, Antonio Caronni, Milena Zanzottera, Cristina Agliardi, Maria Paola Albergoni, Paolo Innocente Banfi, Jorge Navarro, and et al. 2022. "HLA Allele Frequencies and Association with Severity of COVID-19 Infection in Northern Italian Patients" Cells 11, no. 11: 1792. https://doi.org/10.3390/cells11111792