Dose-response relationship between risk factors and incidence of COVID-19 in 325 hospitalized patients: A multicenter retrospective cohort study

Table 1 Characteristics of the patient cohort

Characteristic	All patients (n = 325)	Survivornon-survivor (n = 308); (n = 17)		P value
Age				< 0.0011
Median (IQR)-yr	45.0 (34.0-61.0)	43.0 (33.0-61.0)	63.0 (57.0-76.0)
Distribution-no./total no. (%)
20-49 yr	178	178 (57.8)	0 (0.0)
50-64 yr	91	80 (25.9)	11 (64.7)
≥ 65 yr	56	50 (16.2)	6 (35.3)
Male sex - no./total no. (%)	137 (42.2)	124 (40.3)	13 (76.5)	0.0031
Smoking history - no./total no. (%)	21 (6.5)	18 (5.8)	3 (17.7)	0.054
Exposure to source of transmission within past 14 days - no./total no.				0.0351
Yes	233 (71.7)	222 (4.9)	11 (66.8)
No	92 (28.3)	86 (0.3)	6 (28.0)
Median incubation period (IQR) - days	5.0 ± 4.0	5.0 ± 3.9	5.2 ± 3.5	0.862
Fever on admission
Patients - no./total no. (%)	252 (77.5)	240 (77.9)	12 (70.6)	0.550
Median temperature (IQR) - °C
Distribution of temperature - no./total no. (%)				0.603
< 37.3 °C	77 (23.7)	72 (22.2)	5 (1.5)
37.3-38.0 °C	106 (32.6)	103 (31.7)	3 (0.9)
38.1-39.0 °C	124 (38.2)	116 (35.7)	8 (2.5)
> 39.0°C	18 (5.5)	17 (5.2)	1 (0.3)
Symptoms - no. (%)
Conjunctival congestion	1 (0.31)	1 (0.31)	0 (0.0)	1.000
Headache	52 (16)	51 (16.6)	1 (5.9)	0.243
Cough	207 (63.7)	199 (64.6)	8 (47.1)	0.143
Sputum production	81 (24.9)	76 (24.6)	5 (29.4)	0.660
Fatigue	156 (48)	145 (47.1)	11 (64.7)	0.157
Difficulty breathing	15 (4.6)	13 (4.2)	2 (11.8)	0.149
Shortness of breath	73 (22.5)	68 (22.1)	5 (29.4)	0.0121
Nausea or vomiting	25 (7.7)	21 (6.8)	4 (23.5)	0.0121
Diarrhea	28 (8.6)	27 (8.8)	1 (5.9)	0.680
Myalgia or arthralgia	92 (28.3)	88 (28.5)	4 (23.5)	0.630
Chills	55 (16.9)	54 (17.5)	1 (5.88)	0.212
Coexisting disorder - no. (%)
Fatty liver	15 (4.6)	15 (4.9)	0 (0)	1.000
Chronic obstructive pulmonary disease	17 (5.2)	16 (5.2)	1 (5.9)	0.608
Diabetes	34 (10.5)	27 (8.77)	7 (41.2)	< 0.0011
Hypertension	69 (21.2)	58 (18.8)	11 (64.7)	< 0.0011
Coronary heart disease	9 (2.8)	6 (1.9)	3 (17.7)	< 0.0011
Cerebrovascular disease	18 (5.5)	14 (4.6)	4 (23.5)	0.0101
Hyperlipidemia	17 (5.2)	16 (5.2)	1 (5.8)	0.901
Hepatitis B infection	6 (1.9)	5 (1.6)	1 (5.9)	0.205

¹Quantitative data were presented as mean ± SD (minimum-maximum), while the counting data were presented as count (percentage of the total).

IQR: Inter quartile range.

Table 2 Laboratory findings of the patient cohort

Variable	All patients (N = 325)	Survivor non-survivor (n = 308); (n = 17)		P value
Laboratory findings
White-cell count (109/L)	4.6 (3.3-6.0)	4.6 (3.29-5.9)	6.4 (3.6-7.4)	0.090
Red-cell count (1012/L)	4.3 (4.1-4.7)	4.3 (4.1-4.7)	4.2 (4.0-4.6)	0.557
Hemoglobin (g/L)	131.0 (120.0-142.0)	131.0 (121.0-142.5)	130.0 (114.0-141.0)	0.360
Platelet count (109/L)	171.0 (134.0-202.0)	173.0 (136.0-204.5)	143.0 (119.0-155.0)	0.0081
Hematocrit (%)	39.4 (36.5-42.6)	39.4 (36.6-42.6)	40.0 (34.6-42.6)	0.530
Neutrophil percentage (%)	64.6 (56.8-75.5)	64.5 (56.4-75.2)	73.4 (67.3-81.8)	0.0071
Lymphocyte percentage (%)	26.5 ± 14.5	26.6 ± 12.3	18.6 (11.2-22.5)	0.0081
Monocyte percentage (%)	7.9 ± 3.5	8.1 ± 3.5	6.2 (3.4-6.9)	0.0081
Eosinophil percentage (%)	0.1 (0.0-0.6)	0.1 (0.0-0.55)	0.0 (0.0-0.8)	0.953
Basophil percentage (%)	0.2 (0.1-0.3)	0.2 (0.1-0.3)	0.2 (0.1-0.3)	0.946
Mean red blood cell volume (fL)	90.6 (87.5-93.6)	90.6 (87.6-93.6)	88.9 (85.7-93.1)	0.432
Mean hemoglobin content (pg)	30.0 (28.8-31.1)	30.0 (28.9-31.1)	29.4 (27.5-30.5)	0.209
Mean hemoglobin concentration (g/L)	330.0 (323.0-336.0)	330.0 (323.0-336.0)	324.0 (321.0-331.0)	0.0291
RBC distribution width standard deviation (%)	39.4 (36.7-41.2)	39.2 (36.5-41.2)	40.7 (37.5-42.8)	0.071
RBC distribution width-coefficient of variation (%)	12.7 (12.2-14.4)	12.7 (12.1-14.1)	13.3 (12.6-15.4)	0.116
Neutrophil count (109/L)	2.96 (1.92-4.05)	2.9 (1.9-4.0)	4.1 (2.7-4.9)	0.0351
Lymphocyte count (109/L)	1.13 ± 0.55	1.14 ± 0.55	0.89 ± 0.58	0.0351
Monocyte count (109/L)	0.34 (0.24-0.46)	0.3 (0.3-0.5)	0.3 (0.2-0.5)	0.828
Eosinophil count (109/L)	0.01 (0.0-0.02)	0.01 (0.0-0.02)	0.0 (0.0-0.06)	0.642
Basophil count (109/L)	0.01 (0.01-0.02)	0.01 (0.01-0.02)	0.01 (0.01-0.02)	0.060
Platelet distribution width (%)	12.5 (10.6-16.2)	12.5 (10.6-16.2)	15.1 (10.9-16.4)	0.452
Large platelet ratio (%)	11.1 (9.8-21.2)	11.1 (9.8-21.4)	10.0 (10.0-12.9)	0.405
Mean platelet volume (fL)	19.0 (10.0-28.7)	18.5 (9.9-27.9)	28.9 (18.8-32.4)	0.0181
Platelet hematocrit (%)	0.17 (0.14-0.20)	0.17 (0.14-0.20)	0.13 (0.13-0.16)	0.0161
Distribution of other findings-no./total no. (%)
Systolic blood pressure (mmHg)	123.6 ± 13.6	123.0 ± 12.7	135.4 ± 21.0	0.0221
Diastolic blood pressure (mmHg)	76.4 ± 9.5	76.4 ± 9.3	76.2 ± 13.1	0.464
Blood glucose concentration (mmol/L)	6.4 ± 2.6	6.2 ± 2.3	9.1 ± 4.8	0.0091
Total cholesterol (mmol/L)	3.8 (3.2-4.5)	3.9 (3.3-4.5)	2.7 (2.6-3.3)	0.0031
Triglyceride (mmol/L)	1.1 (0.8-1.4)	1.1 (0.8-1.4)	0.9 (0.8-1.0)	0.455
High density lipoprotein (mmol/L)	1.1 (0.9-1.2)	1.1 (0.9-1.3)	0.97 (0.94-1.12)	0.354
Low density lipoprotein (mmol/L)	2.2 ± 0.7	2.2 ± 0.7	1.5 ± 0.6	0.0021
C-reactive protein (mg/dL)	1.3 (0.3-3.4)	1.3 (0.3-3.0)	5.9 (3.3-8.2)	< 0.0011
Lactate dehydrogenase (U/L)	178.5 (137.5-236.5)	173.0 (136.0-229.0)	275.0 (232.0-324.0)	< 0.0011
Aspartate aminotransferase (U/L)	22.2 (17.1-32.8)	21.7 (16.8-32.3)	31.2 (25.5-36.5)	0.0191
Alanine aminotransferase (U/L)	19.1 (12.8-32.6)	18.9 (12.7-33.2)	19.9 (15.5-29.7)	0.957
γ–Glutamyltransferase (U/L)	19.0 (12.6-38.2)	19.0 (12.4-38.0)	27.8 (16.9-69.0)	0.064
Blood urea nitrogen (mmol/L)	4.1 (3.2-5.3)	4.0 (3.2-5.0)	6.4 (5.3-11.1)	< 0.0011
Creatine kinase (ng/mL)	76.5 (45.0-140.0)	77.1 (45.0-138.0)	74.0 (61.0-203.0)	0.404
Creatinine (μmol/L)	63.9 (53.6-76.7)	63.0 (53.1-74.7)	83.7 (74.9-254.2)	< 0.0011
α-Hydroxybutyrate dehydrogenase (U/L)	137.5 (109.0-176.5)	135.0 (108.0-171.0)	208.0 (158.0-217.0)	0.0011
D-dimer (μg/mL)	0.4 (0.2-0.8)	0.4 (0.2-0.8)	1.1 (0.6-6.3)	< 0.0011
Procalcitonin (ng/mL)	0.05 (0.04-0.09)	0.05 (0.03-0.08)	0.3 (0.1-2.8)	< 0.0011
Brain Natriuretic peptide (pg/mL)	34.4 (13.0-128.0)	31.6 (12.0-108.0)	295.8 (177.0-406.1)	< 0.0011
Antihypertensive drugs				< 0.0011
Yes	57 (17.5)	47 (14.5)	10 (3.0)
No	268 (82.5)	261 (80.3)	7 (2.2)
Hypoglycemic drugs				< 0.0011
Yes	28 (8.6)	22 (6.8)	6 (1.8)
No	297 (91.4)	286 (88)	11 (3.4)
Lipid-lowering drugs				0.0051
Yes	14 (4.3)	11 (3.4)	3 (0.9)
No	311 (95.7)	297 (91.4)	14 (4.3)

¹Indicated statistically significant values (P < 0.05). RBC: Red blood cell.

Table 3 The computed tomography score of the pulmonary involvement in four stages

	Stage-1 (n = 157)	Stage-2 (n = 194)	Stage-3 (n = 165)	Stage-4 (n = 211)	Stage-5 (n = 204)	Stage-6 (n = 137)	P value
Total CT score of the pulmonary involvement	2 ± 4 (0-18)	5 ± 5 (0-22)	7 ± 7 (0-22)	7 ± 7 (0-25)	5 ± 7 (0-24)	4 ± 6 (0-25)	< 0.00011
Number of involved lobes	22 ± 2 (0-5)	3 ± 2 (1-5)	4 ± 2 (1-5)	3 ± 2 (1-5)	3 ± 2 (1-5)	4 ± 2 (1-5)	< 0.00011
CT score in each lobe							< 0.00011
Left upper lobe	0 ± 1 (0-3)	1 ± 2 (0-5)	1 ± 2 (0-5)	1 ± 2 (0-5)	1 ± 2 (0-4)	1 ± 1 (0-5)
Left lower lobe	1 ± 1 (0-5)	1 ± 2 (0-5)	2 ± 2 (0-5)	2 ± 1 (0-5)	1 ± 2 (0-5)	1 ± 2 (0-5)
Right upper lobe	0 ± 1 (0-3)	1 ± 2 (0-5)	1 ± 2 (0-5)	1 ± 2 (0-5)	1 ± 2 (0-5)	1 ± 2 (0-5)
Right middle lobe	0 ± 1 (0-3)	1 ± 1 (0-5)	1 ± 2 (0-5)	1 ± 2 (0-5)	1 ± 1 (0-5)	0 ± 1 (0-5)
Right lower lobe	1 ± 2 (0-12)	2 ± 1 (0-5)	2 ± 2 (0-5)	1 ± 2 (0-5)	1 ± 1 (0-5)	1 ± 1 (0-5)

Quantitative data were presented as mean ± SD (minimum-maximum). Mann-Whitney U test showed significant difference between Stage-1 and Stage-2-6 (P < 0.05); Wilcoxon test showed significant difference between the left lower lobe and the left upper lobe (P < 0.05); Wilcoxon test showed significant difference between the right lower lobe and the right upper/middle lobe (P < 0.05).

¹P < 0.05 by t test.

CT: Computed tomography.

Table 4 Distribution and frequency of the major of lung lesions on computed tomography in different stages defined by the time of onset of symptoms

	Stage-1 (n = 157)	Stage-2 (n = 194)	Stage-3 (n = 165)	Stage-4 (n = 211)	Stage-5 (n = 204)	Stage-6 (n = 137)
Distribution of pulmonary lesions
No lesion	12/157	1/194	0/165	1/211	2/204	0/137
Peripheral	60/157	18/194	55/165	105/211	88/204	66/137
Random	85/157	162/194	88/165	75/211	78/204	44/137
Diffuse	0/157	13/194	22/165	30/211	36/204	27/137
Involvement of the lesions
No involvement	12/157	0/194	0/165	0/211	0/204	0/137
Single lobe	48/157	18/194	11/165	30/211	22/204	11/137
Bilateral multilobe
GGO	96/157	180/194	154/165	180/211	176/204	121/137
None	24/157	0/194	22/165	30/211	47/204	49/137
Yes	133/157	194/194	143/165	181/211	157/204	88/137
Crazy-paving pattern
None	120/157	104/194	110/165	180/211	183/204	126/137
Yes	36/157	90/194	55/165	31/211	121/204	11/137
Consolidation
None	157/157	140/194	88/165	105/211	102/204	89/137
Yes	0/157	54/194	77/165	105/211	102/204	48/137
Fibrosis
None	157/157	180/194	143/165	150/211	102/204	37/137
Yes	0/157	14/194	22/165	61/211	102/204	100/137

The counting data were presented as count (percentage of the total). GGO: Ground glass opacity.

Table 5 Associations of risk factors with incident mortality risk of coronavirus disease 2019

Variable	HR (95%CI)		P for overall association	P for nonlinear association
	Model 1	Model 2
Age (per year increase)	1.06 (1.03, 1.10)	1.04 (1.01, 1.09)	0.080	0.805
CRP (per 1 mg/L increase)	1.15 (1.06, 1.24)	1.10 (1.01, 1.23)	0.062	0.715
DD (per 1 μg/mL increase of NLT	1.89 (1.34, 2.69)	1.63 (1.03, 2.58)	0.012	0.711
LDH (per 10 U/L increase)	1.06 (1.02, 1.09)	1.04 (1.01, 1.10)	0.080	0.805
Procalcitonin (per 1 ng/mL increase of NLT)	2.15 (1.59, 2.90)	1.88 (1.22, 2.88)	0.011	0.721

Hazard ratios are reported per 1-SD increase in loge D-dimer (DD) and Procalcitonin levels; 1-SD higher loge DD and Procalcitonin was approximately equivalent to 2-fold higher DD and Procalcitonin levels.

Model 1: adjusted age, sex.

Model 2: adjusted model 1 plus smoking status, history of hypertension, diabetes, cancers, cardiac disease, and chronic pulmonary disease, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, white blood cell count, C-reactive protein, creatinine, DD, LDH, procalcitonin. CRP: C-reactive protein; DD: D-dimer; LDH: Lactate dehydrogenase; NLT: Natural log-transformation; CI: Confidence interval.

Table 6 Associations of risk factors with severe cases incident risk of coronavirus disease 2019

Variable	OR (95%CI)		P for overall association	P for nonlinear association
	Model 1	Model 2
Age (per year increase)	1.06 (1.04, 1.08)	1.04 (1.01, 1.07)	0.010	0.192
WBC (per 1 × 109/L increase)	1.27 (1.11, 1.46)	1.20 (1.01, 1.45)	0.003	0.046
FBG (per 1 mmol/L increase)	1.19 (1.07, 1.33)	1.15 (1.01, 1.32)	0.036	0.064
Total cholesterol (per 1 mmol/L increase)	1.43 (1.07, 1.91)	1.65 (1.09, 2.50)	0.028	0.260
LDH (per 10 U/L increase)	1.09 (1.05, 1.13)	1.06 (1.02, 1.10)	0.009	0.268
Procalcitonin (per 1 ng/mL increase of NLT)	2.26 (1.68, 3.05)	1.75 (1.16, 2.65)	0.007	0.099

Hazard ratios are reported per 1-SD increase in loge D-dimer (DD) and Procalcitonin levels; 1-SD higher loge DD and procalcitonin was approximately equivalent to 2-fold higher DD and Procalcitonin. Model 1: Adjusted age, sex. Model 2: Adjusted model 1 plus smoking status, history of hypertension, diabetes, cancers, cardiac disease, and chronic pulmonary disease, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, white blood cell count, C-reactive protein, creatinine, DD, LDH, procalcitonin. LDH: Lactate dehydrogenase; NLT: Natural log-transformation. CI: Confidence interval.