Demographic and clinical characteristics
A total of 113 patients with confirmed COVID-19 were included in the study. The demographic and clinical characteristics were summarized in Table 1. The median age of all patients was 48 years (IQR, 34-59). 49.6% of all patients were male. The median age of severe patients was older than that of non-severe patients (median, years, 63 vs 45, p = 0.001). The median weight was 60 kg (53-68). 32 (28.3%) patients were imported cases from Hubei province, 60 (53.1%) had not been to Hubei Province but were infected by patients form Hubei, and the remaining 21 (18.6%) had no clear contact history. A small number of patients had preexisting comorbidities including diabetes (8.8%), hypertension (10.6%), cardiovascular disease (3.5%), COPD (2.7%), Chronic kidney disease (3.5), Chronic liver disease (7.1%) or HIV infection (0.9%). The most common symptom at onset of illness was cough (68 [60.2%]) and fever (50 [44.2%]), but 23% patients had no symptoms at the onset. For the 26 people with no symptoms, 10 cases had early mild lung lesions, and 16 cases had a normal CT. Compared with non-severe cases, severe cases exhibited more diabetes (45.5% vs 4.9%, p=0.001) and symptoms, including fever (90.9% vs 39.2%, p=0.003), chest Congestion (54.5% vs 8.8%, p<0.001), dyspnea (54.5% vs 2.9%, p<0.001). There are different epidemiological histories between severe and non-severe patients (p=0.009).
Table 1. Baseline Characteristics of Patients With COVID-19
Characteristics
|
Total
|
Non-severe
|
Severe
|
P value
|
(n=113)
|
(n=102, 90.3%)
|
(n=11, 9.7%)
|
Age (median [IQR])
|
48.00 [34.0, 59.0]
|
45.00 [31.3, 58.0]
|
63.00 [53.0, 68.5]
|
0.001
|
Sex, N (%)
|
|
|
|
|
Female
|
57 (50.4)
|
52 (51.0)
|
5 (45.5)
|
0.975
|
Male
|
56 (49.6)
|
50 (49.0)
|
6 (54.5)
|
|
Weight (kg, median [IQR])
|
60.0 [53.0, 68.0]
|
60.0 [53.0, 67.6]
|
67.0[57.0, 70.5]
|
0.149
|
Epidemiology information, N (%)
|
|
|
|
|
Without any clear contact history
|
21 (18.6)
|
17 (16.7)
|
4 (36.4)
|
0.009
|
Not been to Hubei, but infected by patients
|
60 (53.1)
|
59 (57.8)
|
1 (9.1)
|
|
From Hubei
|
32 (28.3)
|
26 (25.5)
|
6 (54.5)
|
|
Comorbidities, N (%)
|
|
|
|
|
Diabetes
|
10 (8.8)
|
5 (4.9)
|
5 (45.5)
|
0.001
|
Hypertension
|
12 (10.6)
|
11 (10.8)
|
1 (9.1)
|
1.000
|
Cardiovascular disease
|
4 (3.5)
|
3 (2.9)
|
1 (9.1)
|
0.340
|
COPD
|
3 (2.7)
|
2 (2.0)
|
1 (9.1)
|
0.267
|
Chronic kidney disease
|
4 (3.5)
|
3 (2.9)
|
1 (9.1)
|
0.340
|
Chronic liver disease
|
8 (7.1)
|
7 (6.9)
|
1 (9.1)
|
0.571
|
HIV infection
|
1 (0.9)
|
1 (1.0)
|
0 (0.0)
|
1.000
|
Signs and symptoms, N (%)
|
|
|
|
|
Fever
|
50 (44.2)
|
40 (39.2)
|
10 (90.9)
|
0.003
|
Cough
|
68 (60.2)
|
59 (57.8)
|
9 (81.8)
|
0.223
|
Fatigue
|
31 (27.4)
|
26 (25.5)
|
5 (45.5)
|
0.292
|
Chest Congestion
|
15 (13.3)
|
9 (8.8)
|
6 (54.5)
|
<0.001
|
Dyspnea
|
9 (8.0)
|
3 (2.9)
|
6 (54.5)
|
<0.001
|
Sore throat
|
15 (13.3)
|
13 (12.7)
|
2 (18.2)
|
0.639
|
Diarrhea
|
6 (5.3)
|
6 (5.9)
|
0 (0.0)
|
1.000
|
Myalgia
|
18 (15.9)
|
15 (14.7)
|
3 (27.3)
|
0.378
|
Headache
|
5 (4.4)
|
5 (4.9)
|
0 (0.0)
|
1.000
|
Asymptomatic
|
26 (23.0)
|
26 (25.5)
|
0 (0.0)
|
0.066
|
Laboratory and radiographic findings on admission
As shown in Table 2, lymphocytes (P = 0.001) and white blood cell (p = 0.041) were significantly decreased in severe patients. Compared with non-severe patients, the C-reactive protein (CRP, p < 0.001), procalcitonin (PCT, p = 0.001) and lactate dehydrogenase (LDH, p = 0.027) were significantly increased in severe patients. No significant differences in serum biochemical indexes of the liver (ALT and TBIL) and kidney (BUN and Cr), hemoglobin (HGB), platelet count (PLT), erythrocyte sedimentation rate (ESR) and D-dimer were observed between severe and non-severe patients at admission. Of the chest CT images of the 113 patients, 17 (15%) had no change, 75 (66.4%) were mild, 15 (13.3%) were in advanced stage, and 6 (5.3%) were severe on admission. Figure 1 is a typical patient's chest CT from mild to severe stages.
Table 2. Laboratory and Imaging Characteristics of Patients With COVID-19 on Admission to Hospital.
Characteristics
|
Normal
Range
|
Overall
|
Non-severe
|
Severe
|
P value
|
(n = 113)
|
(n = 102)
|
(n = 11)
|
Laboratory, Median [IQR]
|
|
|
|
|
|
WBC, ×10^9/L
|
3.5 - 9.5
|
4.8 [3.6, 6.1]
|
4.9 [3.8, 6.2]
|
3.3 [2.7, 4.8]
|
0.041
|
N, ×10^9/L
|
1.8 - 6.3
|
2.8 [2.1, 3.6]
|
2.8 [2.1, 3.6]
|
2.1 [1.9, 3.2]
|
0.245
|
L, ×10^9/L
|
1.1 - 3.2
|
1.2 [0.9, 1.7]
|
1.3 [0.9, 1.9]
|
0.7 [0.5, 1.1]
|
0.001
|
HGB, g/L
|
115 - 150
|
130.0 [119.0, 140.0]
|
130.0 [120.2, 140.0]
|
125.0 [115.0, 137.5]
|
0.444
|
PLT, ×10^9/L
|
125 - 350
|
178.0 [128.0, 240.0]
|
181.5 [139.3, 241.5]
|
129.0 [106.5, 208.0]
|
0.243
|
CRP, mg/L
|
0 - 10
|
12.0 [1.7, 33.7]
|
9.4 [1.6, 24.4]
|
52.2 [39.2, 58.6]
|
<0.001
|
PCT, ng/mL
|
< 0.05
|
0.05 [0.04, 0.08]
|
0.05 [0.04, 0.07]
|
0.09 [0.08, 0.11]
|
0.001
|
ESR, mm/h
|
10.0 - 20.0
|
34.0 [16.0, 45.0]
|
34.0 [15.0, 45.0]
|
42.0 [31.0, 64.5]
|
0.058
|
AST, U/L
|
13 - 35
|
25.7 [19.4, 31.2]
|
25.1 [19.2, 30.3]
|
29.8 [26.5, 41.1]
|
0.035
|
ALT, U/L
|
7 - 40
|
20.8 [14.4, 30.8]
|
20.3 [14.4, 30.0]
|
30.5 [15.5, 51.0]
|
0.257
|
TBIL, µmol/L
|
1.7 - 25.0
|
14.3 [10.0, 20.0]
|
14.2 [10.6, 19.3]
|
14.9 [9.6, 22.6]
|
0.892
|
CK, U/L
|
40 - 200
|
81.1 [54.2, 128.7]
|
79.3 [51.2, 124.5]
|
109.7 [69.7, 205.9]
|
0.145
|
CK-MB, U/L
|
0 - 24
|
13.1 [10.2, 17.1]
|
13.1 [10.1, 17.1]
|
11.6 [11.2, 15.3]
|
0.907
|
LDH, U/L
|
120 - 250
|
203.9 [167.7, 250.8]
|
195.2 [167.0, 243.5]
|
269.2 [219.6, 333.2]
|
0.027
|
BUN, mmol/L
|
2.6 - 7.5
|
4.2 [3.5, 5.4]
|
4.0 [3.4, 5.0]
|
4.7 [4.4, 6.4]
|
0.043
|
CR, µmol/L
|
41 - 73
|
63.7 [53.8, 76.0]
|
63.7 [53.5, 74.6]
|
78.6 [57.3, 99.2]
|
0.104
|
D-dimer, mg/L
|
0 - 500
|
230.0 [160.0, 367.0]
|
230.0 [160.0, 350.0]
|
340.0 [185.0, 630.0]
|
0.167
|
Imaging diagnosis, N (%)
|
|
|
|
|
|
Normal
|
|
17 (15.0)
|
17 (16.7)
|
0 (0.0)
|
<0.001
|
Early
|
|
75 (66.4)
|
75 (73.5)
|
0 (0.0)
|
|
Advanced
|
|
15 (13.3)
|
10 (9.8)
|
5 (45.5)
|
|
Severe
|
|
6 (5.3)
|
0 (0.0)
|
6 (54.5)
|
|
Abbreviations: WBC, white blood cell; N, neutrophil count; L, lymphocyte count; HGB, hemoglobin; PLT, platelet count; CRP, C-reactive protein; PCT, procalcitonin; ESR, erythrocyte sedimentation rate; AST, glutamic oxaloacetic transaminase; ALT, aspartate aminotransferase; TBIL, total bilirubin abnormal; CK, creatine kinase; CK-MB, creatine kinase-MB; LDH, lactate dehydrogenase; BUN, Blood Urea Nitrogen; CR, creatinine.
Disease progression, complications, treatment and clinical outcomes
As shown in Table 3, the duration of fever (7 vs 2, p = 0.02), days from symptom onset to virus clearance (24 vs 15.5, p < 0.001), days from symptom onset to pneumonia resolution (28 vs 17, p <0.001) and length of hospital stay (21 vs 11, p < 0.001) were longer among severe patients than non-severe patients. In the hospitalization and follow-up period, the complications of COVID-19 were assessed, including secondary bacterial infections (8%), pulmonary fibrosis (2.7%) and acute respiratory distress syndrome (ARDS) (8%). All the above-mentioned complications were more common in 11 severe cases, compared with non-severe cases (all P<0.05). Antiviral drugs were used specifically to treat COVID-19 during hospitalization, including lopinavir/ritonavir (77.9%), arbidol (90.3%), oseltamivir (39.8%) and chloroquine (10%). For severe cases, methylprednisolone (1-2 mg/kg/d) for 3-5 days combined with human gamma-globulin (10-20 g/d) was prescribed. Seven patients received ICU care, and 3 cases received invasive mechanical ventilation. Interferon inhalation was used in almost all patients. As of March 8, 2020, 113 (100%) of 113 patients had met the discharge criteria. 0 (0%) patients died.
Table 3. Disease Progression, Complications, Treatments and Outcome of Patients With COVID-19
Characteristics
|
Overall
|
Non-severe
|
Severe
|
P value
|
(n = 113)
|
n = (102)
|
n = (11)
|
Disease progression, median [IQR]
|
|
|
|
|
Duration of fever
|
3.0 [0.0, 4.0]
|
2 [0.0, 4.0]
|
7.0 [4.0, 8.0]
|
0.02
|
Peak temperature
|
37.3 [36.8, 38.4]
|
37.0 [36.8, 38.0]
|
38.5 [38.2, 39.0]
|
0.001
|
From onset to hospitalization
|
6.0 [3.0, 9.0]
|
5.0 [3.0, 9.8]
|
6.0 [4.5, 7.0]
|
0.946
|
From onset to viral clearance
|
16.0 [12.0, 22.0]
|
15.5 [11.0, 20.8]
|
24.0 [20.5, 28.5]
|
<0.001
|
From onset to pneumonia resolution
|
18.0 [12.0, 24.0]
|
17.0 [11.3, 22.0]
|
28.0 [25.0, 40.5]
|
<0.001
|
Length of hospital stay
|
12.0 [9.0, 18.0]
|
11.0 [9.0, 16.0]
|
21.0 [18.0, 32.5]
|
<0.001
|
Complications, N (%)
|
|
|
|
|
Secondary bacterial infections
|
9 (8.0)
|
2 (2.0)
|
7 (63.6)
|
<0.001
|
Pulmonary fibrosis
|
3 (2.7)
|
0 (0.0)
|
3 (27.3)
|
0.001
|
ARDS
|
9 (8.0)
|
2 (2.0)
|
7 (63.6)
|
<0.001
|
Shock
|
1 (0.9)
|
0 (0.0)
|
1 (9.1)
|
0.097
|
Treatment, N (%)
|
|
|
|
|
Lopinavir/ritonavir
|
88 (77.9)
|
78 (76.5)
|
10 (90.9)
|
0.475
|
Arbidol
|
102 (90.3)
|
92 (90.2)
|
10 (90.9)
|
1
|
Oseltamivir
|
45 (39.8)
|
37 (36.3)
|
8 (72.7)
|
0.043
|
Chloroquine
|
10 (8.8)
|
10 (9.8)
|
0 (0.0)
|
0.597
|
Gamma-globulin
|
23 (20.4)
|
13 (12.7)
|
10 (90.9)
|
<0.001
|
Corticosteroid
|
10 (8.8)
|
1 (1.0)
|
9 (81.8)
|
<0.001
|
Need ICU care
|
7 (6.2)
|
0 (0.0)
|
7 (63.6)
|
<0.001
|
Invasive mechanical ventilation
|
3 (2.7)
|
0 (0.0)
|
3 (27.3)
|
0.001
|
Outcome, N (%)
|
|
|
|
|
Discharge
|
113 (100)
|
102 (90.3)
|
11 (9.7)
|
0.172
|
Risk factors for severe cases
In the multivariable binary stepwise logistic regression model, variables such as secondary bacterial infections (OR 3.43; 95% CI 3.69-6.53), duration of virus clearance (OR 1.16; 95% CI 1.04-1.34), CRP (OR 1.04; 95% CI 1.01-1.08) were significantly associated with severe cases with COVID-19 (Table 4).
Table 4. Risk factors associated with progression to severity
Variables
|
OR (95% CI)
|
P value
|
Secondary bacterial infections
|
3.43 (3.69-6.53)
|
0.005
|
From onset to viral clearance (d)
|
1.16 (1.04-1.34)
|
0.018
|
Fever
|
4.00 (1.70-5.95)
|
0.071
|
CRP
|
1.04 (1.01-1.08)
|
0.032
|
Note: Multivariable binary stepwise logistic regression analysis was used to assess risk factors associated with progression to severity, with factors included age, gender, weight, epidemiology information, comorbidity, fever, lymphocyte count (L), C-reactive protein (CRP), lactate dehydrogenase (LDH), duration of virus clearance, secondary bacterial infections.
Factors affecting virus clearance
In order to assess factors affecting virus clearance, duration of virus clearance is converted into an ordered variable: ≤15d, 15-30d, >30d. The Kruskal-Wallis test found that the rate of patient progress to severe clinical condition was correlated with the duration of virus clearance (P = 0.0025), as shown in Figure 2. In ordered logistic regression model, comorbidity was the only independent prognostic factor of viral clearance (OR 4.85; 95% CI 1.11-22.07, P = 0.037) (Table 5).
Table 5. Factors Associated with Viral Clearance in Ordered Logistic Regression Analysis.
Variables
|
OR (95% CI)
|
P value
|
Age
|
1.01 (0.99-1.04)
|
0.335
|
Gender (Male)
|
0.46 (0.20-1.03)
|
0.060
|
Epidemiology information
|
|
|
Not been to Hubei vs Without any clear contact history
|
2.12 (0.63-7.44)
|
0.231
|
From Hubei vs Not been to Hubei
|
0.84 (0.24-2.95)
|
0.781
|
Comorbidity
|
4.85 (1.11-22.07)
|
0.037
|
Fever
|
1.49 (0.64-3.52)
|
0.354
|
Secondary bacterial infections
|
0.94 (0.14-6.72)
|
0.954
|
Imaging diagnosis
|
|
|
Early vs Normal
|
1.53 (0.40-5.93)
|
0.529
|
Advanced vs Early
|
2.05 (0.30-14.38)
|
0.465
|
Severe vs Advanced
|
4.17 (0.28-62.31)
|
0.296
|
L
|
1.13 (0.85-1.50)
|
0.380
|
CRP
|
1.01 (0.99-1.03)
|
0.356
|
LDH
|
0.99 (0.99,1.00)
|
0.275
|
Weight
|
0.99 (0.96-1.02)
|
0.582
|
Note: Duration of virus clearance is converted into an ordered variable: ≤15d, 15-30d, >30d.
Abbreviations: L, lymphocyte count; CRP, C-reactive protein; LDH, lactate dehydrogenase.