Background
Methods
Patients enrollment
Data collection
Statistical analysis
Sparse principal component analysis (SPCA) and model evaluation
Independent cohort validation
Results
Demographics and baseline laboratory test results
Mild (N = 54) | Severe (N = 28) | P | |
---|---|---|---|
Gender = male (%) | 28 (51.9) | 23 (82.1) | 0.015 |
Smoke = yes (%) | 2 (3.7) | 0 (0.0) | 0.782 |
Cough = yes (%) | 42 (77.8) | 20 (71.4) | 0.716 |
Fever = yes (%) | 46 (85.2) | 22 (78.6) | 0.656 |
Comorbidity = yes (%) | 8 (14.8) | 16 (57.1) | < 0.001 |
Age | 40.00 (28.25–50.00) | 55.50 (44.75–65.75) | < 0.001 |
Blood routine test | |||
WBC (× 109/L) | 4.64 (4.04–5.64) | 6.52 (5.13–7.25) | 0.004 |
NEU% | 62.50 (51.38–71.40) | 80.50 (73.92–87.62) | < 0.001 |
NEU (× 109/L) | 2.69 (2.08–3.76) | 5.21 (3.93–6.37) | < 0.001 |
MONO% | 7.45 (5.55–8.57) | 5.60 (4.45–7.95) | 0.043 |
MONO (× 109/L) | 0.35 (0.26–0.45) | 0.34 (0.24–0.56) | 0.754 |
LYM% | 27.45 (21.10–37.72) | 12.90 (7.45–18.62) | < 0.001 |
LYM (× 109/L) | 1.29 (0.85–1.75) | 0.82 (0.49–1.09) | < 0.001 |
RBC (× 1012/L) | 4.62 (4.13–5.00) | 4.51 (4.37–4.78) | 0.685 |
Hemaglobin (g/L) | 140.00 (122.00–153.75) | 140.50 (129.00–144.50) | 0.591 |
Hematocrit (%) | 0.41 (0.37–0.46) | 0.42 (0.39–0.43) | 0.46 |
PLT (× 109/L) | 163.50 (135.50–224.25) | 162.00 (128.75–202.75) | 0.345 |
Coagulation test | |||
APTT (s) | 38.70 (35.23–43.63) | 35.80 (29.67–39.82) | 0.019 |
TT (s) | 13.90 (13.20–14.70) | 14.45 (13.85–14.95) | 0.045 |
Fibrinogen(g/L) | 2.73 (1.88–3.40) | 3.58 (3.19–4.31) | < 0.001 |
PT (s) | 14.45 (13.43–16.38) | 14.05 (13.28–14.95) | 0.177 |
D-dimer (µg/L) | 0.19 (0.08–0.28) | 0.45 (0.23–0.66) | < 0.001 |
Clinical chemistry test | |||
TBIL (µmol/L) | 14.20 (11.20–18.20) | 14.75 (9.78–20.23) | 0.728 |
DBIL (µmol/L) | 5.30 (4.40–6.40) | 5.80 (4.68–8.97) | 0.096 |
ALT (U/L) | 19.00 (14.00–35.00) | 29.00 (23.75–42.25) | 0.009 |
AST (U/L) | 24.00 (20.00–34.00) | 31.50 (23.00–39.50) | 0.023 |
GGT (U/L) | 22.00 (17.00–37.00) | 42.00 (27.75–64.50) | < 0.001 |
ALP (U/L) | 60.00 (48.00–71.00) | 60.00 (42.75–81.25) | 0.713 |
Total protein (g/L) | 72.90 (68.60–75.80) | 70.25 (66.75–73.45) | 0.13 |
Albumin (g/L) | 44.90 (42.10–48.20) | 38.15 (36.00–40.85) | < 0.001 |
Glucose (mmol/L) | 5.87 (5.34–6.82) | 7.19 (6.43–9.83) | < 0.001 |
Urea (mmol/L) | 3.59 (3.02–4.56) | 5.71 (4.42–6.58) | < 0.001 |
Creatinine (µmol/L) | 69.00 (59.00–82.00) | 70.00 (59.50–76.25) | 0.941 |
Uric acid (µmol/L) | 259.00 (206.00–301.00) | 204.50 (139.75–296.50) | 0.068 |
Carbon dioxide (mmol/L) | 25.30 (23.80–27.40) | 25.70 (23.37–27.93) | 0.728 |
Potassium (mmol/L) | 3.99 (3.71–4.33) | 3.97 (3.76–4.09) | 0.538 |
Sodium (mmol/L) | 138.00 (137.00–139.00) | 137.00 (134.00–138.00) | 0.002 |
Chlorine (mmol/L) | 102.40 (100.90–104.00) | 101.05 (97.95–102.82) | 0.009 |
Calcium (mmol/L) | 2.27 (2.18–2.32) | 2.12 (2.08–2.19) | < 0.001 |
Phosphorus (mmol/L) | 1.10 (0.97–1.20) | 0.96 (0.89–1.14) | 0.029 |
Magnesium (mmol/L) | 0.87 (0.82–0.95) | 0.92 (0.83–1.00) | 0.06 |
Creatine kinase (U/L) | 91.70 (55.10–150.10) | 87.00 (61.05–167.65) | 0.996 |
CKMB (U/L) | 11.20 (9.10–15.80) | 10.00 (9.00–13.00) | 0.273 |
LDH (U/L) | 205.00 (173.00–269.00) | 284.00 (251.50–331.50) | < 0.001 |
Myohemoglobin (ng/mL) | 30.00 (27.00–33.00) | 36.00 (30.00–68.00) | 0.004 |
Infection-related biomarkers | |||
Procalcitonin (ng/mL) | 0.14 (0.10–0.16) | 0.18 (0.13–0.23) | 0.002 |
Interleukin-6 (pg/ml) | 6.20 (5.25–6.83) | 7.26 (6.66–9.91) | < 0.001 |
SAA (mg/L) | 75.00 (18.43–175.40) | 167.50 (118.50–209.88) | < 0.001 |
CRP (mg/L) | 5.25 (2.00–21.93) | 43.40 (14.52–96.05) | < 0.001 |
Results of Sparse principal component analysis (SPCA)
Odd ratio | 95% confidence interval | P value | |
---|---|---|---|
PC1 | 4.049 | 1.126–21.015 | 0.057 |
PC2 | 0.563 | 0.239–1.940 | 0.182 |
PC3 | 1.446 | 0.791–2.938 | 0.256 |
PC4 | 0.749 | 0.300–1.501 | 0.478 |
PC5 | 3.486 | 1.057–14.825 | 0.059 |
PC6 | 1.730 | 0.572–5.837 | 0.344 |
PC7 | 0.675 | 0.285–1.347 | 0.296 |
PC8 | 1.635 | 0.652–12.627 | 0.486 |
PC9 | 0.793 | 0.298–2.051 | 0.624 |
PC10 | 3.329 | 1.122–13.325 | 0.053 |
PC11 | 0.712 | 0.317–1.548 | 0.390 |
PC12 | 3.318 | 1.260–11.949 | 0.041 |
PC13 | 0.898 | 0.405–1.970 | 0.783 |
Prediction efficiency evaluation
Cutoff | AUC(95% CI) | ACC(95% CI) | SEN(95% CI) | SPE(95% CI) | PPV(95% CI) | NPV(95% CI) | |
---|---|---|---|---|---|---|---|
Model-A | 0.125 | 0.867 (0.786–0.947) | 0.726 (0.721–0.731) | 1 (1–1) | 0.574 (0.433–0.716) | 0.565 (0.422–0.708) | 1 (1–1) |
LMN | 0.281 | 0.837 (0.75–0.925) | 0.793 (0.789–0.797) | 0.786 (0.634–0.938) | 0.796 (0.689–0.904) | 0.667 (0.506–0.828) | 0.878 (0.786–0.969) |
ALB | 42.05 | 0.846 (0.758–0.934) | 0.79 (0.786–0.794) | 0.821 (0.68–0.963) | 0.774 (0.661–0.886) | 0.657 (0.5–0.814) | 0.891 (0.801–0.981) |
CD4 | 352.5 | 0.773 (0.656–0.89) | 0.721 (0.715–0.728) | 0.75 (0.577–0.923) | 0.703 (0.555–0.85) | 0.621 (0.444–0.797) | 0.812 (0.677–0.948) |
CD8 | 146.5 | 0.809 (0.701–0.917) | 0.77 (0.765–0.776) | 0.625 (0.431–0.819) | 0.865 (0.755–0.975) | 0.75 (0.56–0.94) | 0.78 (0.654–0.907) |
CRP | 7.6 | 0.811 (0.716–0.906) | 0.683 (0.678–0.688) | 0.964 (0.896–1.033) | 0.537 (0.404–0.67) | 0.519 (0.383–0.655) | 0.967 (0.902–1.031) |
DD | 0.44 | 0.754 (0.641–0.868) | 0.756 (0.752–0.761) | 0.536 (0.351–0.72) | 0.88 (0.79–0.97) | 0.714 (0.521–0.908) | 0.772 (0.663–0.881) |
IL6 | 7.005 | 0.8 (0.691–0.909) | 0.805 (0.801–0.809) | 0.607 (0.426–0.788) | 0.907 (0.83–0.985) | 0.773 (0.598–0.948) | 0.817 (0.719–0.915) |
Lym | 1.235 | 0.75 (0.641–0.86) | 0.646 (0.641–0.652) | 0.857 (0.728–0.987) | 0.537 (0.404–0.67) | 0.49 (0.35–0.63) | 0.879 (0.767–0.99) |
Lym% | 21 | 0.833 (0.742–0.924) | 0.793 (0.789–0.797) | 0.857 (0.728–0.987) | 0.759 (0.645–0.873) | 0.649 (0.495–0.802) | 0.911 (0.828–0.994) |
Neu | 3.825 | 0.786 (0.675–0.898) | 0.768 (0.764–0.773) | 0.786 (0.634–0.938) | 0.759 (0.645–0.873) | 0.629 (0.468–0.789) | 0.872 (0.777–0.968) |
Neu% | 69.75 | 0.833 (0.745–0.922) | 0.756 (0.752–0.761) | 0.857 (0.728–0.987) | 0.704 (0.582–0.825) | 0.6 (0.448–0.752) | 0.905 (0.816–0.994) |
NLR | 3.531 | 0.851 (0.765–0.937) | 0.817 (0.814–0.821) | 0.857 (0.728–0.987) | 0.796 (0.689–0.904) | 0.686 (0.532–0.84) | 0.915 (0.835–0.995) |
Independent cohort validation
Cutoff | AUC(95% CI) | AUC(95% CI) | SEN(95% CI) | SPE(95% CI) | PPV(95% CI) | NPV(95% CI) | |
---|---|---|---|---|---|---|---|
Model-A | 0.484 | 0.835 (0.774–0.895) | 0.835 (0.774–0.895) | 0.831 (0.735–0.926) | 0.718 (0.634–0.802) | 0.612 (0.506–0.719) | 0.888 (0.822–0.953) |
LMN | 0.711 | 0.8 (0.733–0.868) | 0.8 (0.733–0.868) | 0.729 (0.615–0.842) | 0.745 (0.664–0.827) | 0.606 (0.492–0.719) | 0.837 (0.764–0.91) |
ALB | 38.25 | 0.816 (0.742–0.891) | 0.816 (0.742–0.891) | 0.769 (0.655–0.884) | 0.788 (0.71–0.867) | 0.645 (0.526–0.764) | 0.872 (0.805–0.94) |
CD4 | 308 | 0.708 (0.624–0.791) | 0.708 (0.624–0.791) | 0.625 (0.498–0.752) | 0.731 (0.646–0.816) | 0.556 (0.433–0.678) | 0.784 (0.702–0.865) |
CD8 | 176 | 0.694 (0.608–0.781) | 0.694 (0.608–0.781) | 0.554 (0.423–0.684) | 0.75 (0.667–0.833) | 0.544 (0.415–0.673) | 0.757 (0.674–0.84) |
CRP | 8.15 | 0.7 (0.618–0.781) | 0.7 (0.618–0.781) | 0.724 (0.609–0.839) | 0.578 (0.485–0.671) | 0.477 (0.373–0.582) | 0.797 (0.709–0.886) |
DD | 0.99 | 0.758 (0.675–0.841) | 0.758 (0.675–0.841) | 0.615 (0.483–0.748) | 0.823 (0.747–0.899) | 0.653 (0.52–0.786) | 0.798 (0.719–0.877) |
Lym | 0.605 | 0.785 (0.714–0.855) | 0.785 (0.714–0.855) | 0.593 (0.468–0.719) | 0.872 (0.809–0.934) | 0.714 (0.588–0.841) | 0.798 (0.726–0.87) |
Lym% | 13.95 | 0.788 (0.716–0.859) | 0.788 (0.716–0.859) | 0.746 (0.635–0.857) | 0.743 (0.661–0.825) | 0.611 (0.499–0.724) | 0.844 (0.771–0.916) |
Neu | 5.055 | 0.71 (0.625–0.794) | 0.71 (0.625–0.794) | 0.729 (0.615–0.842) | 0.661 (0.572–0.749) | 0.538 (0.428–0.647) | 0.818 (0.738–0.899) |
Neu% | 78.4 | 0.775 (0.701–0.849) | 0.775 (0.701–0.849) | 0.763 (0.654–0.871) | 0.706 (0.621–0.792) | 0.584 (0.474–0.694) | 0.846 (0.772–0.92) |
NLR | 5.691 | 0.784 (0.711–0.856) | 0.784 (0.711–0.856) | 0.746 (0.635–0.857) | 0.743 (0.661–0.825) | 0.611 (0.499–0.724) | 0.844 (0.771–0.916) |