Quantitative assessment of lung lesions
The AI algorithm was employed to quantitatively evaluate the lung lesion on CT, and the distribution of lung lesions in COVID-19 patients is shown in Table 1. The median lesion ratio and median lesion volume of the whole lung were 4.1% (IQR 0.5–12.9) and 153.9 ml (IQR, 20.8–426.2), respectively. A larger proportion and volume of lung lesions were observed in the right lung, rather than in the left lung. Of the total five lung lobes, the highest proportion and volume of lung lesions were found in the right lower lobe. The median ratio and the median volume of lung lesions in the right lower lobe were 5.9% (IQR 0.3–22.8%) and 48.5 ml (IQR 2.7–149.6), respectively.
Table 1
Distribution of the lung lesion on CT quantitatively assessed by AI algorithm
Lesion location | Lesion ratio (%), median (IQR) n = 1630 | Lesion volume (ml), median (IQR) n = 1630 |
Whole lung | 4.1 (0.5, 12.9) | 153.9 (20.8, 426.2) |
Left lung | 2.4 (0.2, 9.8) | 41.6 (3.8, 156.8) |
Right lung | 4.3 (0.4, 14.6) | 85.9 (8.8, 264.0) |
Left upper lobe | 1.1 (0.1, 6.9) | 10.7 (0.6, 61.9) |
Left lower lobe | 2.7 (0.2, 14.4) | 19.8 (1.2, 87.6) |
Right upper lobe | 1.8 (0, 11.7) | 13.6 (0.4, 85.3) |
Right middle lobe | 0.6 (0, 6.4) | 2.2 (0, 26.3) |
Right lower lobe | 5.9 (0.3, 22.8) | 48.5 (2.7, 149.6) |
IQR, interquartile range |
Characteristics of COVID-19 patients with different level of lung lesion ratio
A total of 1630 hospitalised COVID-19 patients were included in this study, and with respect to the whole lung lesion ratio, 128 (7.9%), 1336 (82.0%), 139 (8.5%), and 27 (1.7%) patients were categorised into none, mild, intermediate, and severe groups, respectively (2). The demographics, initial symptoms, and comorbidities of the patients are presented in Table 2. Of all 1630 cases, the median age was 62 years (IQR 52–69), and 839 patients (51.5%) were male. The proportions of smokers and drinkers were 5.6% and 3.2%, respectively. No differences were found in sex and smoking status among the four groups. The highest median age was observed in the intermediate group. With the gradually worsening of lung lesions in the four groups, the frequency of fever, cough, shortness of breath, fatigue, and chest distress increased accordingly, and the highest proportion of myalgia was found in the intermediate group. Discrepancies were not observed in the other initial symptoms. The highest proportions of hypertension, diabetes, anemia, and stroke were found in the intermediate group. Other comorbidities among the four groups showed no significant differences.
Table 2
Baseline characteristics of the patients
Baseline parameters | All patients (n = 1630) | None (n = 128) | Mild (n = 1336) | Intermediate (n = 139) | Severe (n = 27) | p |
Demographics | | | | | | |
Age (y); median (IQR) | 62 (52, 69) | 48 (37, 58) | 62 (54, 69) | 66 (57, 72) | 62 (50, 71) | < 0.001 |
Male, no (%) | 839 (51.5) | 55 (43.0) | 696 (52.1) | 73 (52.5) | 15 (55.6) | 0.245 |
Smoking, no (%) | 92 (5.6) | 4 (3.1) | 81 (6.1) | 5 (3.6) | 2 (7.4) | 0.359 |
Drinking, no (%) | 52 (3.2) | 2 (1.6) | 48 (3.6) | 0 (0) | 2 (7.4) | 0.047 |
Initial symptoms | |
Fever, no (%) | 1166 (71.5) | 74 (57.8) | 964 (72.2) | 104 (74.8) | 24 (88.9) | 0.001 |
Cough, no (%) | 1108 (68.0) | 65 (50.8) | 917 (68.6) | 103 (74.1) | 23 (85.2) | < 0.001 |
Expectoration, no (%) | 232 (14.2) | 9 (7.0) | 201 (15.0) | 17 (12.2) | 5 (18.5) | 0.071 |
Shortness of breath, no (%) | 662 (40.6) | 31 (24.2) | 536 (40.1) | 78 (56.1) | 17 (63.0) | < 0.001 |
Myalgia, no (%) | 437 (26.8) | 19 (14.8) | 363 (27.2) | 47 (33.8) | 8 (29.6) | 0.005 |
Fatigue, no (%) | 578 (35.5) | 25 (19.5) | 482 (36.1) | 57 (41.0) | 14 (51.9) | < 0.001 |
Diarrhea, no (%) | 72 (4.4) | 5 (3.9) | 61 (4.6) | 6 (4.3) | 0 (0) | 0.705 |
Nausea, no (%) | 51 (3.1) | 2 (1.6) | 44 (3.3) | 5 (3.6) | 0 (0) | 0.546 |
Headache, no (%) | 46 (2.8) | 5 (3.9) | 36 (2.7) | 4 (2.9) | 1 (3.7) | 0.872 |
Loss of appetite, no (%) | 63 (3.9) | 2 (1.6) | 54 (4.0) | 5 (3.6) | 2 (7.4) | 0.411 |
Chest distress, no (%) | 135 (8.3) | 8 (6.3) | 106 (7.9) | 15 (10.8) | 6 (22.2) | 0.030 |
Comorbidities | |
Hypertension, no (%) | 537 (32.9) | 23 (18.0) | 444 (33.2) | 59 (42.5) | 11 (40.7) | < 0.001 |
Arrhythmia, no (%) | 45 (2.8) | 0 (0) | 38 (2.8) | 6 (4.3) | 1 (3.7) | 0.171 |
Diabetes, no (%) | 266 (16.3) | 6 (4.7) | 222 (16.6) | 32 (23.0) | 6 (22.2) | < 0.001 |
Coronary artery disease, no (%) | 103 (6.3) | 2 (1.6) | 92 (6.9) | 8 (5.8) | 1 (3.7) | 0.111 |
Hyperlipemia, no (%) | 27 (1.7) | 3 (2.3) | 23 (1.7) | 1 (0.7) | 0 (0) | 0.657 |
COPD, no (%) | 67 (4.1) | 2 (1.6) | 58 (4.3) | 6 (4.3) | 1 (3.7) | 0.510 |
Cancer, no (%) | 35 (2.2) | 2 (1.6) | 30 (2.3) | 2 (1.4) | 1 (3.7) | 0.822 |
Chronic liver disease, no (%) | 46 (2.8) | 5 (3.9) | 37 (2.8) | 3 (2.2) | 1 (3.7) | 0.835 |
Chronic kidney disease, no (%) | 13 (0.8) | 0 (0) | 12 (0.9) | 1 (0.7) | 0 (0) | 0.699 |
Anemia, no (%) | 26 (1.6) | 1 (0.8) | 18 (1.4) | 6 (4.3) | 1 (3.7) | 0.039 |
Stroke, no (%) | 53 (3.3) | 2 (1.6) | 41 (3.1) | 10 (7.2) | 0 (0) | 0.028 |
Gout, no (%) | 22 (1.4) | 0 (0) | 18 (1.4) | 4 (2.9) | 0 (0) | 0.207 |
Gastritis , no (%) | 34 (2.1) | 3 (2.3) | 26 (2.0) | 4 (2.9) | 1 (3.7) | 0.815 |
IQR, interquartile range; COPD, Chronic obstructive pulmonary disease |
Laboratory findings on admission in COVID-19 patients with different levels of lung lesion ratios were studied (Table 3). With the augment of lung lesion ratio in the four groups, the levels of plasma fibrinogen, plasma D-dimer, serum lactate dehydrogenase, serum α-hydroxybutyrate dehydrogenase, serum high-sensitive cardiac troponin I, serum myoglobin, serum B-type natriuretic peptide, serum procalcitonin, serum hsCRP, peripheral blood leukocyte count, peripheral blood neutrophil percentage and prothrombin time increased gradually. Accordingly, the levels of peripheral blood hemoglobin, serum total protein, serum albumin, activated partial thromboplastin time, and peripheral blood lymphocyte percentage gradually decreased. The highest levels of serum alanine aminotransferase and serum creatinine kinase-myocardial band were observed in the severe group and the highest levels of serum aspartate transaminase, serum γ-glutamyltransferase, serum urea nitrogen, serum cystatin C and thrombin time were found in the intermediate group.
Table 3
Laboratory features of Covid-19 patients with different levels of whole lung lesion ratio
Laboratory parameters | All patients (n = 1630) | None (n = 128) | Mild (n = 1336) | Intermediate (n = 139) | Severe (n = 27) | p |
Coagulation profile | |
Prothrombin time (s) | 12.8 (12.2, 13.5) | 12.8 (12.3, 13.5) | 12.8 (12.2, 13.4) | 13.4 (12.5, 14.4) | 13.7 (12.5, 15.4) | < 0.001 |
Activated partial thromboplastin time (s) | 28.0 (26.1, 30.1) | 28.5 (26.9, 30.0) | 28.0 (26.1, 30.1) | 27.3 (25.5, 29.9) | 27.1 (23.8, 29.1) | 0.016 |
Fibrinogen (g/L) | 3.0 (2.6, 3.4) | 2.7 (2.4, 3.0) | 3.0 (2.6, 3.4) | 3.4 (3.0, 3.8) | 3.4 (2.8, 4.1) | < 0.001 |
Thrombin time (s) | 15.2 (14.5, 16.0) | 14.9 (14.2, 15.5) | 15.2 (14.5, 16.0) | 15.7 (14.7, 16.5) | 15.1 (14.5, 16.6) | < 0.001 |
D-dimer (mg/L) | 0.4 (0.2, 0.9) | 0.2 (0.2, 0.3) | 0.4 (0.2, 0.8) | 1.1 (0.6, 2.7) | 1.1 (0.7, 3.9) | < 0.001 |
Complete blood count | |
Leucocytes count (109/L) | 5.7 (4.7, 7.1) | 5.7 (4.8, 6.9) | 5.7 (4.7, 7.0) | 6.6 (5.2, 8.0) | 8.3 (6.0, 10.5) | < 0.001 |
Neutrophil percentage (%) | 62.0 (55.6, 69.1) | 59.3 (54.2, 64.9) | 61.7 (55.5, 68.0) | 68.9 (60.5, 77.5) | 75.5 (57.2, 82.7) | < 0.001 |
Lymphocyte percentage (%) | 26.9 (20.5, 32.7) | 30.2 (25.8, 35.6) | 27.1 (21.3, 32.8) | 19.7 (13.4, 27.0) | 14.1 (9.3, 29.0) | < 0.001 |
Monocyte percentage (%) | 7.7 (6.5, 9.0) | 7.1 (6.1, 8.3) | 7.8 (6.5, 9.1) | 7.7 (6.3, 9.2) | 7.1 (5.5, 8.2) | 0.002 |
Eosinophil percentage (%) | 2.0 (1.2, 3.3) | 2.1 (1.5, 3.3) | 2.1 (1.2, 3.3) | 1.8 (1.0, 3.2) | 2.0 (1.6, 3.1) | 0.454 |
Basophil percentage (%) | 0.4 (0.2, 0.5) | 0.4 (0.3, 0.5) | 0.4 (0.2, 0.6) | 0.3 (0.2, 0.5) | 0.3 (0.2, 0.5) | 0.043 |
Platelet count (109/L) | 224.0 (183.0, 270.5) | 213.5 (184.0, 251.8) | 223.5 (182.8, 271.0) | 234.3 (184.0, 283.6) | 228.5 (189.0, 292.0) | 0.308 |
Hemoglobin (g/L) | 123.0 (113.0, 134.0) | 128.5 (118.8, 139.0) | 123.0 (112.0, 134.0) | 120.0 (109.2, 129.0) | 117.0 (109.5, 128.0) | < 0.001 |
Biochemical parameters | |
Alanine aminotransferase (IU/L) | 23.0 (14.7, 38.3) | 23.5 (12.2, 38.2) | 22.6 (14.7, 37.4) | 27.4 (18.0, 48.1) | 30.6 (15.4, 41.4) | 0.010 |
Aspartate transaminase (IU/L) | 19.6 (15.7, 26.4) | 19.7 (15.7, 25.0) | 19.3 (15.6, 26.1) | 21.9 (17.3, 31.4) | 20.5 (15.7, 29.8) | 0.006 |
Total protein (g/L) | 64.8 (60.7, 68.6) | 67.7 (63.9, 70.3) | 64.9 (60.8, 68.4) | 61.8 (58.2, 66.9) | 59.6 (57.3, 64.0) | < 0.001 |
Albumin (g/L) | 37.6 (34.8, 40.2) | 40.5 (38.6, 42.4) | 37.7 (35.1, 40.1) | 34.6 (31.6, 37.5) | 34.2 (31.4, 37.4) | < 0.001 |
Total bilirubin (µmol/L) | 9.3 (7.2, 12.1) | 10.6 (8.5, 12.7) | 9.1 (7.1, 12.1) | 9.2 (7.1, 12.1) | 10.5 (7.2, 12.3) | 0.009 |
γ-glutamyltransferase (IU/L) | 30.2 (20.4, 50.6) | 23.3 (16.8, 37.2) | 30.1 (20.3, 49.3) | 39.2 (25.4, 64.9) | 35.7 (26.7, 68.1) | < 0.001 |
Urea nitrogen (mmol/L) | 4.4 (3.7, 5.5) | 4.2 (3.4, 5.1) | 4.4 (3.6, 5.4) | 4.8 (3.9, 6.2) | 4.5 (3.9, 6.1) | 0.007 |
Creatinine (µmol/L) | 64.5 (55.4, 75.4) | 64.1 (54.2, 75.2) | 64.8 (55.7, 75.5) | 62.5 (54.6, 78.2) | 59.3 (50.5, 66.5) | 0.120 |
Cystatin C (mg/L) | 0.94 (0.84, 1.08) | 0.85 (0.77, 0.94) | 0.94 (0.84, 1.08) | 1.0 (0.86, 1.19) | 0.94 (0.88, 1.12) | < 0.001 |
Lactate dehydrogenase (IU/L) | 176.7 (152.3, 211.3) | 156.4 (134.6, 178.1) | 174.9 (151.9, 205.2) | 222.7 (184.4, 268.6) | 246.4 (209.2, 333.2) | < 0.001 |
Myocardial injury markers | |
α-hydroxybutyrate dehydrogenase (IU/L) | 143.9 (123.9, 172.8) | 125.0 (106.8, 141.4) | 142.6 (123.9, 167.7) | 179.2 (148.5, 225.5) | 196.8 (166.4, 271.1) | < 0.001 |
Creatinine kinase-myocardial band (IU/L) | 8.5 (6.9, 10.8) | 8.1 (6.8, 10.6) | 8.5 (6.9, 10.6) | 8.4 (7.0, 11.5) | 10.0 (7.6, 13.0) | 0.102 |
High-sensitive cardiac troponin I (ng/mL) | 0.01 (0.01, 0.01) | 0.01 (0.01, 0.01) | 0.01 (0.01, 0.01) | 0.01 (0.01, 0.013) | 0.011 (0.010, 0.025) | 0.008 |
Myoglobin (ng/mL) | 5.2 (2.2, 9.0) | 5.0 (2.8, 8.7) | 5.1 (1.9, 8.7) | 5.8 (4.0, 10.2) | 8.4 (4.8, 13.2) | 0.009 |
B-type natriuretic peptide (pg/mL) | 0.01 (0.01, 29.48) | 0.01 (0.01, 0.01) | 0.01 (0.01, 27.29) | 22.16 (0.01, 74.87) | 36.29 (9.99, 59.49) | < 0.001 |
Inflammation markers | |
Procalcitonin (ng/mL) | 0.04 (0.03, 0.08) | 0.03 (0.03, 0.05) | 0.04 (0.03, 0.07) | 0.07 (0.04, 0.11) | 0.08 (0.06, 0.37) | < 0.001 |
High-sensitive C-reactive protein (mg/L) | 2.4 (0.8, 8.5) | 0.8 (0.3, 2.4) | 2.2 (0.8, 7.3) | 10.9 (3.2, 35.4) | 12.2 (3.6, 48.3) | < 0.001 |
Association between laboratory findings and lung lesion ratio
The linear regression analysis between the whole lung lesion ratio and laboratory findings showed that the levels of plasma fibrinogen (r = 0.280, p < 0.001), plasma D-dimer (r = 0.248, p < 0.001), peripheral blood neutrophil percentage (r = 0.243, p < 0.001), serum hsCRP (r = 0.212, p < 0.001), serum lactate dehydrogenase (r = 0.375, p < 0.001), serum α-hydroxybutyrate dehydrogenase (r = 0.363, p < 0.001), and peripheral blood leukocyte count (r = 0.194, p < 0.001) were positively correlated with the lesion ratio of the whole lung. The levels of serum albumin (r=-0.300, p < 0.001) and peripheral blood lymphocyte rate (r = 0.272, p < 0.001) were negatively correlated with the lesion ratio of the whole lung (Fig. 1 and Supplementary Material online Table S1). Stepwise multivariate regression analysis revealed that the plasma fibrinogen level (β = 0.183, p < 0.001), plasma D-dimer (β = 0.167, p < 0.001), serum albumin (β=-0.195, p < 0.001), serum α-hydroxybutyrate dehydrogenase (β = 0.222, p < 0.001), and peripheral blood leukocyte count (β = 0.073, p = 0.026) were independently correlated with the lesion ratio of the whole lung (Supplementary Material online Table S1).
Baseline determinants of lung lesion severity
Ordinal logistic regression was employed to evaluate the correlation of demographics, initial symptoms, and comorbidities (baseline variables) with the severity of lung lesions (an ordinal outcome variable). According to the results of the parallel line test (p value of parallel line test < 0.05), age, drinking, and expectoration were not applicable to the ordinal logistic regression. In the univariate and multivariate analysis (Table 4), male, smoking and drinking were not found associated with the severity of lung lesion; however, fever (odds ratio [OR], 1.428; 95% confidence interval [CI], 1.064–1.916; p = 0.018), cough (OR, 1.470; 95% CI, 1.099–1.966; p = 0.009), shortness of breath (OR, 1.765; 95% CI, 1.328–2.344; p < 0.001), fatigue (OR, 1.363; 95% CI, 1.024–1.813; p = 0.033), hypertension (OR, 1.570; 95% CI, 1.183–2.083; p = 0.002), diabetes (OR, 1.650; 95% CI, 1.168–2.335; p = 0.005), and anemia (OR, 3.497; 95% CI, 1.428–8.559; p = 0.006) were confirmed to be independent risk factors associated with the severity of lung lesion (Table 4). The OR in patients with shortness of breath to develop into more severe lung lesions is 1.765 (1.328–2.344) over subjects without shortness of breath. The patients with anemia were 3.497 (95% CI 1.428–8.559) times more likely to develop into more severe lung lesions, compared to patients without anemia.
Table 4
Ordinal logistic regression analyses of baseline dterminants with the severity of lung lesions
Variables | Univariate Analysis | | Multivariate Analysis |
p value of parallel line test | p value | OR (95% CI) | | p value | OR (95% CI) |
Age | < 0.001 | < 0.001 | 0.950 (0.942, 0.960) | | Not applicable |
Male | 0.426 | 0.118 | 1.223 (0.950, 1.573) | | Not selected |
Smoking | 0.167 | 0.828 | 1.062 (0.617, 1.828) | | Not selected |
Drinking | 0.002 | 0.726 | 0.880 (0.430, 1.802) | | Not selected |
Fever | 0.114 | < 0.001 | 1.662 (1.251, 2.208) | | 0.018 | 1.428 (1.064, 1.916) |
Cough | 0.190 | < 0.001 | 1.868 (1.415, 2.467) | | 0.009 | 1.470 (1.099, 1.966) |
Expectoration | 0.039 | 0.213 | 1.255 (0.878, 1.791) | | Not selected |
Shortness of breath | 0.864 | < 0.001 | 2.172 (1.667, 2.841) | | < 0.001 | 1.765 (1.328, 2.344) |
Myalgia | 0.250 | 0.001 | 1.621 (1.221, 2.151) | | —— |
Fatigue | 0.089 | < 0.001 | 1.707 (1.309, 2.228) | | 0.033 | 1.363 (1.024, 1.813) |
Diarrhea | 0.281 | 0.821 | 0.931 (0.505, 1.719) | | Not selected |
Nausea | 0.717 | 0.365 | 1.380 (0.687, 2.773) | | Not selected |
Headache | 0.776 | 0.710 | 0.866 (0.405, 1.853) | | Not selected |
Loss of appetite | 0.358 | 0.283 | 1.416 (0.751, 2.672) | | Not selected |
Chest distress | 0.320 | 0.027 | 1.644 (1.059, 2.555) | | —— |
Coronary artery disease | 0.031 | 0.306 | 1.303 (0.784, 2.166) | | Not selected |
Hypertension | 0.284 | < 0.001 | 1.790 (1.366, 2.347) | | 0.002 | 1.570 (1.183, 2.083) |
Arrhythmia | 0.120 | 0.039 | 2.100 (1.037, 4.255) | | —— |
Diabetes | 0.059 | < 0.001 | 1.968 (1.412, 2.743) | | 0.005 | 1.650 (1.168, 2.335) |
Hyperlipemia | 0.681 | 0.228 | 0.553 (0.211, 1.449) | | Not selected |
COPD | 0.365 | 0.335 | 1.357 (0.731, 2.519) | | Not selected |
Cancer | 0.633 | 0.929 | 1.040 (0.438, 2.469) | | Not selected |
Chronic liver disease | 0.861 | 0.469 | 0.755 (0.353, 1.614) | | Not selected |
Chronic kidney disease | 0.289 | 0.684 | 1.331 (0.335, 5.296) | | Not selected |
Anemia | 0.876 | 0.009 | 3.136 (1.331, 7.389) | | 0.006 | 3.497 (1.428, 8.559) |
Stroke | 0.134 | 0.031 | 2.061 (1.069, 3.971) | | —— |
Gout | 0.187 | 0.095 | 2.305 (0.865, 6.147) | | Not selected |
Gastritis | 0.753 | 0.598 | 1.262 (0.532, 2.995) | | Not selected |
CI, confidence interval; COPD, Chronic obstructive pulmonary disease; “Not applicable” indicates the variable not applicable to the ordinal logistic regression for the p value of parallel line test < 0.05. |
The lesion ratio of the right lung, left lung, and the whole lung in patients with or without cough, shortness of breath, hypertension, diabetes, or anemia are shown in Fig. 2. Patients with one of the aforementioned initial symptoms or comorbidities had higher lesion ratios in the whole lung, right lung, and right lung, compared to those in the patients without these initial symptoms or comorbidities.