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Out of 302 patients, 8 patients were excluded due to missing data, 90 patients (30.5%) were diagnosed with severe illness, and 17 (5.8%) patients with critical illness, while the remainder (188/295, 63.7%) had moderate illness based on the new coronavirus pneumonia diagnosis and treatment plan (trial version 7; National Health Committee of the People's Republic of China). Our data demonstrated an overall mortality rate of 5.08%. Overall, the median age of patients in the study was 60 (49−68) years, and the median age in the non-severe and severe group was 57.0 (46.7−67.0) years and 62.5 (55.7−70.0) years, respectively, and the difference was statistically significant (P = 0.002). One hundred and sixty-four (55.6%) patients were male and showed a significant difference between the moderate, severe and critical groups (P < 0.001). There was no significant difference in cardiovascular disease, digestive system disease, endocrine system disease, malignant tumor, nervous system disease, or respiratory system disease. Fever, cough, and tachypnea were the most common clinical symptoms. Laboratory findings are shown in Table 1.
Clinical symptoms Points Confusion 1 Urea > 7 mmol/L 1 Age over 65 years 1 Respiratory rate ≥ 30 1 Systolic blood pressure ≤ 90 mmHg or diastolic blood pressure ≤ 60 mmHg 1 Table S1. CURB-65 scoring system
Variables All patients (n = 294) Mild group (n = 188) Severe group (n = 106) P Age, years 60.00 (49.00−68.00) 57.00 (46.00−67.00) 62.50 (55.75−70.00) 0.002 Gender Female 131 (44.6) 98 (52.1) 33 (31.1) 0.001 Male 163 (55.4) 90 (47.9) 73 (668.9) Signs and symtons Fever 93 (31.6) 62 (33.0) 31 (29.2) 0.509 Cough 176 (60.1) 113 (60.1) 63 (60.0) 0.984 Tachypnea 79 (26.9) 42 (22.3) 37 (34.9) 0.020 Muscle soreness 2 (0.7) 0 2 (1.1) 0.539 Headache 3 (1.0) 3 (1.6) 0 0.555 Sore throat 4 (1.4) 3 (1.6) 1 (0.9) > 0.999 Chest pain 1 (0.3) 1 (0.5) 0 > 0.999 Diarrhea 5 (1.7) 3 (1.6) 2 (1.9) > 0.999 Nausea and vomiting 2 (0.7) 1 (0.5) 1 (1.0) 1.000 Vital signs Body temperature, °C 36.70 (36.50−37.20) 36.70 (36.50−37.50) 36.60 (36.50−37.00) 0.843 Heart rate, beats/min 88 (80−99) 88 (80−98) 88 (84−99) 0.180 Respiratory rate breaths/min 22 (20−23) 22 (20−23) 22 (20−23) 0.050 Systolic Blood pressure, mmHg 127 (116−138) 125 (115−136) 132 (120−138) 0.014 Diastolic Blood pressure, mmHg 80 (74.00−89.00) 80 (73.75−87.25) 81 (74.25−90.50) 0.610 Laboratory results White blood cell count, ×109/L 5.52 (4.40−7.63) 5.18 (4.14−6.63) 6.78 (5.10−9.03) < 0.001 Red blood cell count, ×109/L 4.15 (3.83−4.54) 4.19 (3.88−4.51) 4.08 (3.73−4.55) 0.209 Hematokrit, % 37.80 (34.90−40.80) 38.00 (35.80−40.75) 37.05 (34.02−40.80) 0.066 Platelet count, ×109/L 210.00 (161.00−275.00) 207.00 (160.50−270.00) 216.50 (166.75−283.25) 0.469 Platelet distribution width, % 16.20 (16.00−16.50) 16.20 (16.00−16.50) 16.30 (16.02−16.60) 0.337 Mean platelet volume, fl 9.50 (8.90−10.30) 9.50 (8.90−10.40) 9.50 (8.80−10.10) 0.284 Thrombocytocrit 0.21 (0.16−0.26) 0.21 (0.16−0.26) 0.21 (0.17−0.25) 0.637 Mean corpuscular volume, fl 91.00 (88.40−93.40) 91.00 (88.45−93.30) 91.05 (88.05−93.77) 0.943 Mean corpuscular Hemoglobin, pg 30.40 (29.50−31.00) 30.40 (29.55−31.00) 30.50 (29.42−31.10) 0.773 Mean corpuscular−hemoglobin
concentration, g/L332.00 (327.00−339.00) 332.00 (326.00−339.00) 333.00 (328.00−338.75) 0.643 RDW-CV, fL 12.30 (11.90−12.90) 12.30 (11.90−12.80) 12.50 (11.90−13.00) 0.032 RDW-SD, fL 40.00 (38.60−41.90) 40.00 (38.55−41.75) 40.25 (38.70−42.40) 0.227 Neutrophil cell count, ×109 /L 3.77 (2.79−5.67) 3.34 (2.46−4.63) 5.25 (3.60−7.53) < 0.001 Neutrophil granulocyte rate, % 69.50 (61.70−79.60) 66.80 (57.05−73.65) 78.95 (68.50−85.20) < 0.001 Lymphocyte count, ×109/L 1.08 (0.81−1.53) 1.24 (0.90−1.64) 0.90 (0.60−1.25) < 0.001 Lymphocyte percentage, % 21.40 (13.60−28.60) 24.70 (17.70−33.10) 13.65 (8.62−22.18) < 0.001 Monocytes count, ×109/L 0.39 (0.27−0.50) 0.38 (0.27−0.48) 0.41 (0.27−0.54) 0.293 Monocyte percentage, % 6.80 (5.30−8.70) 7.10 (5.80−8.75) 6.10 (4.55−8.17) 0.002 Eosinophils count, ×109/L 0.03 (0.00−0.08) 0.03 (0.01−0.09) 0.02 (0.00−0.08) 0.277 Eosinophils percentage, % 0.50 (0.10−1.50) 0.70 (0.10−1.60) 0.40 (0.00−1.20) 0.062 Basophil count, ×109/L 0.01 (0.01−0.02) 0.01 (0.01−0.02) 0.01 (0.01−0.03) 0.066 Basophil percentage, % 0.30 (0.10−0.40) 0.30 (0.10−0.40) 0.20 (0.10−0.40) 0.328 Hemoglobin, g/L 126.00 (115.00−136.00) 128.00 (118.00−136.00) 123.00 (113.75−136.00) 0.075 Platelet count, ×109/L 210.00 (161.00−275.00) 207.00 (160.50−270.00) 216.50 (166.75−283.25) 0.469 IL-6, pg/mL 8.24 (6.42−11.90) 7.69 (6.13−11.15) 89.04 (7.05−12.87) 0.004 Amyloid A, mg/L 142.35 (11.00−234.28) 55.30 (5.77−218.12) 181.30 (82.38−245.81) < 0.001 α-fucosidase, U/L 22.50 (19.00−27.00) 22.50 (18.00−27.00) 22.50 (20.00−26.25) 0.522 D-dimer level, mg/L 0.70 (0.38−1.57) 0.51 (0.31−1.06) 1.18 (0.60−3.57) < 0.001 Total protein, g/L 65.13 ± 6.50 66.28 ± 6.30 63.07 ± 6.36 < 0.001 Albumin, g/L 33.18 ± 4.63 34.72 ± 4.37 30.43 ± 3.72 < 0.001 Globulin, g/L 31.50 (28.87, 34.40) 31.40 (28.60−34.10) 32.40 (29.50−35.00) 0.089 ALB, g/L 1.00 (0.90−1.20) 1.10 (1.00−1.30) 0.90 (0.80−1.10) < 0.001 Prealbumin, g/L 153.50 (99.00−223.25) 166.50 (117.75−232.00) 130.50 (84.75−193.50) < 0.001 Total cholesterol, mmol/L 3.84 (3.36−4.44) 3.94 (3.45−4.45) 3.71 (3.21−4.44) 0.176 High-sensitivity troponin, ng/L 3.60 (1.40−8.90) 2.80 (1.10−6.10) 6.60 (2.65−12.65) < 0.001 Prothrombin time, S 11.30 (10.62−12.00) 11.20 (10.50−11.80) 11.70 (10.80−12.60) < 0.001 Prothrombin time activity, % 102.70 (89.00−121.90) 108.10 (93.30−124.30) 96.20 (77.90−118.30) < 0.001 INR 0.96 (0.91−1.02) 0.96 (0.90−1.01) 0.99 (0.92−1.06) 0.003 Thrombin time, S 17.00 (16.10−18.00) 17.15 (16.20−17.78) 17.00 (16.00−18.30) 0.678 Ferritin, ug/L 473.90 (243.69−737.52) 380.65 (191.88−623.12) 688.59 (438.28−1022.66) < 0.001 Alkaline phosphatase, U/L 76.00 (59.75−93.25) 76.00 (59.50−94.50) 75.00 (60.00−93.00) 0.856 r-glutamyltransferase, U/L 34.00 (21.00−60.00) 28.00 (18.00−56.00) 41.00 (26.00−77.00) < 0.001 Egfr 106.33 (91.19−125.93) 107.69 (92.72−128.03) 104.53 (86.69−124.48) 0.080 Aminotransferase Alanine, U/L 32.00 (20.00−48.50) 28.00 (18.50−45.00) 38.00 (24.00−53.00) 0.006 Aminotransferase Aspartate, U/L 32.00 (24.00−45.25) 29.00 (23.00−41.00) 37.00 (29.00−56.00) < 0.001 Total Bilirubin, mmol/L 12.80 (9.57−16.55) 13.10 (9.70−16.70) 12.00 (9.10−16.00) 0.207 Indirect Bilirubin, mmol/L 8.30 (6.18−11.43) 8.80 (6.60−11.75) 7.80 (5.65−10.60) 0.047 Direct Bilirubin, mmol/L 4.00 (3.00−5.23) 4.00 (2.90−5.10) 4.00 (3.20−5.40) 0.647 Lactate dehydrogenase, U/L 255.00 (197.50−350.50) 225.00 (180.50−277.50) 344.00 (261.00−452.00) < 0.001 Uric acid, μmol/L 233.00 (188.57−300.25) 239.00 (194.50−302.00) 224.00 (181.00−294.00) 0.237 Cystatin C, mg/L 0.85 (0.74−1.03) 0.83 (0.73−0.95) 0.94 (0.78−1.16) < 0.001 Glucose, mmol/L 5.80 (5.00−7.10) 5.60 (5.00−6.68) 6.30 (5.30−7.80) 0.005 Cholinesterase, U/L 7914.35 ± 2021.09 8395.58 ± 1947.16 7081.45 ± 1878.61 < 0.001 Creatine kinase, U/L 70.00 (47.75−115.00) 68.50 (46.75−106.00) 74.00 (51.50−126.00) 0.225 Creatinine, μmol/L 67.40 (57.00−80.25) 65.90 (55.75−77.85) 70.90 (59.90−83.60) 0.009 Blood urea nitrogen, mmol/L 4.35 (3.46−5.46) 4.00 (3.30−5.00) 4.90 (4.00−6.60) < 0.001 CXR
0
1
2280
80 (28.6)
20 (7.1)
180 (61.22)177
63 (35.6)
18 (10.2)
96 (54.2)103
17 (16.5)
2 (1.89)
84 (81.6)< 0.001
< 0.001
0.227
< 0.001Note. Data are presented as n/N (%) and mean ± SD, median (IQR). P values were calculated by Chi-square test, Fisher's exact test, t test, or Wilcoxon rank sum test as appropriate. P values denoted the comparison among mild group and severe group. CXR, chest CT abnormalities. Table 1. Clinical characteristics among patients with COVID-19 in the cohort
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A total of 74 variables were documented on hospital admission and were measured in the LASSO regression. Following the application of LASSO regression and L1-penalized least absolute shrinkage and selection regression for multivariable analyses, we used 10 fold-cross validation to obtain a training and validation set from the whole dataset. We then repeated the LASSO and logistic regression analyses which resulted in 3 variables which predicted the development of severe illness (Figure 1A, 1B), which were the NLR (OR, 1.27; 95% CI, 1.15−1.39), albumin (OR, 0.76; 95% CI, 0.70−0.83), chest CT abnormalities (OR, 2.01; 95% CI, 1.41−2.86) (Table 2).
Figure 1. Predictive risk factors were selected by LASSO regression analysis. (A) LASSO coefficient profiles of the non-zero variables in COVID-19 patients. (B) The lowest point of the red curve indicates the mean−squared error plot, which contains thirteen variables. A more concise model including five variables is the dashed line on the right within one standard error. (C) Nomogram predicting the risk of developing severe COVID-19. LASSO, least absolute shrinkage and selection operator; NLR, neutrophil-to-lymphocyte ratio; CXR, chest CT abnormalities.
Variables OR (95% CI) P NLR 1.27 (1.15, 1.39) 0.038 Albumin 0.76 (0.70, 0.83) < 0.001 CXR 2.01 (1.41, 2.86) < 0.001 Note. LASSO, least absolute shrinkage and selection operator; NLR, neutrophil-to-lymphocyte ratio; CXR, chest CT abnormalities. Table 2. Selected variables by LASSO
CURB-65 Risk 0−1 Low risk ≥ 2 Moderate and high risk Table S2. CURB-65 risk score
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The nomogram was constructed based on the coefficients of the predictors (Figure 1C). This allowed clinicians to evaluate the possibility of developing severe COVID-19. The nomogram had a C-index of 0.822 (95% CI, 0.7667–0.8776) (Figure 2A, 2B). In the case of a P < 0.05 for non-linearity, the restricted cubic spline (RCS) was drawn to demonstrate the relationship between the NLR (P < 0.001) and albumin (P < 0.001) and the risk, which is non-linear (Figure 2C, 2D). The clinical impact and decision curve indicated that a combination of the risk factors had a good net benefit and influence on the patients (Figure 2E, 2F), (Supplementary Tables S1–S2 available in www.besjournal.com).
Figure 2. Association of variables with the risk of severe illness and accuracy of the model. (A–B) The calibration curve and ROC curve of the new model. The C-index was 0.822, the specificity was 0.648 and the sensitivity was 0.814. (C–D) Association of albumin and NLR with the risk of severe illness in patients with COVID-19. (E–F) Decision curve and clinical impact curve of the new complex model in the nomogram for no severe illness survival in patients with COVID-19, compared with actual survival and CURB-65, in which the possibility of survival had a superior standardized net benefit.
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During internal validation, the training set was applied and the calibration curve showed convergence of the predicted rates and actual results (Figure 3). In the external validation, the validation set was applied and the AUC of severe COVID-19 was 0.885 (95% CI, 0.7719–0.9666).
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Characteristics of the Study
Selection of Risk Factors
Construction of a Nomogram
Validation
21273Supplementary Materials.pdf |