Risk factors associated with acute respiratory distress syndrome in COVID-19 patients outside Wuhan: A double-center retrospective cohort study of 197 cases in Hunan, China

Table 1 Clinical characteristics and factors associated respiratory distress syndrome

Demographic characteristics	All patients (n = 197)	Non-ARDS (n = 184)	ARDS (n = 13)	P value
Ages (yr)	45.0 (34.0-58.5)	42 (34-57)	58 (48-65)	0.010
Sex
Male	93/197 (47.2%)	85/184 (46.2%)	8/13 (61.5%)	0.284
Female	104/197 (52.8%)	99/184 (53.8%)	5/13 (38.5%)
Body mass index	23.42 (21.39-25.69)	23.29 (21.29-25.49)	26.03 (21.50-26.89)	0.170
Smoking	11/171 (6.4%)	10/159 (6.3%)	1/12 (8.3%)	0.5621
Travelling to Wuhan	45/133 (33.8%)	40/125 (32.0%)	5/8 (62.5%)	0.167
Imported cases	76/183 (41.5%)	73/184 (39.7%)	3/12 (25.0%)	0.481
Cluster exposure history	132/197 (67.0%)	127/184 (69.0%)	5/13 (38.5%)	0.050
Coexisting disease
Any	49/197 (24.9%)	42/184 (22.8%)	7/13 (53.8%)	0.030
Heart disease	8/197 (4.0%)	6/184 (3.3%)	2/13 (15.4%)	0.0901
Hypertension	27/197 (13.7%)	24/184 (13.0%)	3/13 (23.1%)	0.549
Diabetes	13/197 (6.6%)	12/184 (6.5%)	1/13(7.7%)	0.600
Other	25/197 (12.7%)	22/184 (12.0%)	3/13 (23.1%)	0.464
Clinical manifestations
Fever
37.3–39.0 °C	115/197 (58.4%)	107/184 (58.2%)	8/13 (61.5%)	0.308
> 39.0 °C	17/197 (8.6%)	14/184 (7.6%)	3/13 (23.0%)
Non-fever	68/197 (34.5%)	65/184 (35.3%)	3/13 (23.0%)	0.551
Fever	129/197 (65.5%)	119/184 (64.7%)	10/13 (76.9%)
Cough	147/197 (74.6%)	137/184 (74.5%)	10/13 (76.9%)	1.000
Expectoration	76/197 (38.6%)	71/184 (38.6%)	7/13 (53.8%)	0.277
Dyspnea	39/197 (19.8%)	29/184 (15.8%)	10/13 (58.8%)	< 0.001
Diarrhea	27/197 (13.7%)	26/184 (14.1%)	1/13 (7.7%)	0.814
Nausea/vomit	17/197 (8.6%)	16/184 (8.7%)	1/13 (7.7%)	1.000
Fatigue	70/197 (35.5%)	64/184 (34.8%)	6/13 (46.2%)	0.597
Sore throat	18/197 (9.1%)	18/184 (9.8%)	0/13 (0.0%)	0.493
Headache	19/197 (9.6%)	18/184 (9.8%)	1/13 (7.7%)	1.000
Muscular soreness	15/197 (7.6%)	14/184 (7.6%)	1/13 (7.7%)	1.0001
Total complications	21/197 (10.7%)	14/184 (7.6%)	7/13 (53.8%)	< 0.001
Dry/moist rales	11/162 (6.8%)	8/153 (5.2%)	3/9 (33.3%)	0.016
CT imagings
Single lung involvement	23/169 (13.6%)	23/150 (%)	0/13 (%)	0.268
Bilateral lung involvement	140/169 (82.8%)	127/150	13/13 (100.0%)
Ground glass opacities	143/165 (86.7%)	137/145 (94.5%)	6/9 (66.7%)	0.0181
Consolidative/mixed opacities	11/165 (6.7%)	8/145 (5.5%)	3/9 (33.3%)
Number of lobe involvement
Single left lobe	58/158 (36.7%)	55/111 (49.5%)	3/8 (37.5%)	0.770
Double left lobe	61/158 (38.6%)	56/111 (50.5%)	5/8 (62.5%)
Single or double right lobe	65/157 (41.4%)	62/113 (54.9%)	3/8 (37.5%)	0.558
Triple right lobe	56/157 (35.7%)	51/113 (45.1%)	5/8 (62.5%)
Laboratory findings				P value
White cell count (× 109/L)	4.75 (3.44-5.91)	4.75 (3.44-5.89)	4.51 (3.06-7.05)	0.990
< 4	71/197 (36.0%)	66/184 (35.9%)	5/13 (38.5%)	0.293
4-10	122/197 (61.9%)	115/184 (62.5%)	7/13 (53.8%)
> 10	4/197 (2.0%)	3/184 (1.6%)	1/13 (7.7%)
Neutrophil (× 109/L)	2.89 (2.16-3.72)	2.88 (2.15-3.65)	3.31 (2.16-5.46)	0.260
< 2	40/197 (20.3%)	37/184 (20.1%)	3/13 (23.1%)	0.325
2-7	152/197 (77.2%)	143/184 (77.7%)	9/13 (69.2%)
> 7	5/197 (2.5%)	4/184 (2.2%)	1/13 (7.7%)
Lymphocyte (× 109/L)	1.20 (0.81-1.66)	1.21 (0.88-1.69)	0.70 (0.60-0.94)	< 0.001
< 0.8	47/197 (23.9%)	38/184 (20.7%)	9/13 (69.2%)	< 0.001
Hemoglobin (g/L)	130.00 (119.00-141.00)	130.00 (119.25-140.75)	127.50 (103.25-148.00)	0.511
< 110 g/L	18/197 (9.1%)	16/184 (8.7%)	2/13 (15.4%)	0.756
Blood platelet	173.00 (139.00-230.00)	178.50 (139.00-229.50)	148.00 (91.25-225.25)	0.174
< 100, × 109/L	12/197 (6.1%)	10/184 (5.4%)	2/13 (15.4%)	0.1821
Prothrombin time (s)	11.5 (10.90-12.35)	11.55 (10.90-12.30)	11.40 (10.60-12.75)	0.964
> 16 s	21.1 (%)	1/184 (0.5%)	1/13 (7.7%)	0.128
APTT (s)	32.20 (29.80-34.75)	32.40 (30.20-34.57)	29.70 (26.90-35.90)	0.212
< 22	3/1971.5 (%)	2/184 (1.0%)	1/13 (%)	0.186
CK (U/L)	64.10 (41.97-93.87)	63.85 (41.17-91.85)	83.20 (47.00-187.30)	0.195
> 170 U/L	19/192 (9.9%)	15/182 (8.2%)	4/10 (40.0%)	0.010
CK-MB (U/L)	9.10 (5.90-12.05)	8.60 (5.60-11.90)	14.10 (10.43-30.50)	0.005
> 23	12/193 (6.2%)	19/183 (10.4%)	4/10 (40.0%)	0.021
D-dmier (mg/L)	0.26 (0.13-0.58)	0.26 (0.12-0.56)	1.17 (0.26-8.57)	0.001
> 0.5	52/165 (31.5%)	44/153 (28.8%)	8/12 (66.7%)	0.016
Albumin (g/L)	38.28 (35.35-41.08)	38.52 (35.78-41.59)	29.90 (27.86-34.88)	< 0.001
< 35	38/197 (19.3%)	26/155 (16.8%)	9/13 (69.2%)	< 0.001
ALT (U/L)	20.13 (14.12-30.29)	19.72 (13.91-28.75)	37.41 (23.93-78.65)	< 0.001
> 40	32/197 (16.2%)	26/184 (14.1%)	6/13 (46.2%)	0.008
AST (U/L)	23.38 (19.14-31.28)	23.12 (18.98-30.49)	33.24 (21.47-68.61)	0.029
> 40	24/197 (12.2%)	18/184 (9.8%)	6/13 (46.2%)	0.001
Total bilirubin (μmol/L)	10.80 (7.89-15.12)	10.67 (7.82-14.86)	13.26 (8.81-23.31)	0.114
> 17.1	40/197 (20.3%)	36/184 (19.6%)	4/13 (30.8%)	0.539
Creatinine (μmol/L)	64.10 (41.98-93.88)	51.25 (40.39-64.65)	46.17 (36.79-111.57)	0.684
> 133	6/197 (3.0%)	4/184 (2.2%)	2/13 (15.4%)	0.052
LDH (U/L)	161.15 (135.80-208.88)	157.80 (133.85-205.97)	313.60 (183.55-352.50)	< 0.001
> 250 U/L	25/197 (12.7%)	17/184 (9.2%)	8/13 (61.5%)	< 0.001
CRP (mg/L)	12.79 (3.55-28.50)	12.47 (3.49-25.52)	45.70 (13.30-72.08)	0.003
> 10	10/105 (53.3%)	96/184 (52.2%)	9/13 (69.2%)	0.064
Procalcitonin (μg/L)	0.08 (0.06-0.20)	0.70 (0.05-0.18)	0.80 (0.60-71.83)	0.117
> 0.5	4/187 (2.1%)	1/175 (0.6%)	2/12 (16.7%)	0.0111
Blood glucose (mmol/L)	161/197 (81.7%)	5.32 (4.73-6.66)	6.03 (5.01-12.97)	0.169
> 7	31/161 (19.3%)	28/154 (18.2%)	3/7 (42.9%)	0.259
Treatments
Oxygen therapy
Mechanical ventilation	4/164 (2.0%)	0/155 (0.0%)	4/9 (44.4%)	< 0.0011
Nasal cannula	151/164 (92.1%)	146/155 (94.2%)	5/9 (55.6%)
Did not oxygen therapy	9/164 (5.5%)	9/155 (5.8%)	0/9 (0.0%)
Antiviral therapy	161/162 (99.4%)	153/154 (99.4%)	8/8 (100.0%)	1.0001
Antibiotic therapy	67/153 (43.8%)	62/147 (42.2%)	5/6 (83.3%)	0.116
Corticosteroid	40/161 (24.8%)	30/151 (19.9%)	10/10 (100.0%)	< 0.001
Convalescent plasma	4/197 (2.0%)	0/184 (0.0%)	4/13 (30.8%)	< 0.0011
Gamma globulin	39/157 (24.8%)	32/150 (21.3%)	7/7 (100.0%)	< 0.001

¹Fisher exact test.

LDH: Lactate dehydrogenase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LDH: Lactate dehydrogenase; CRP: C-reactive protein; LPV/r: Lopinavir/ritonavir; APTT: Activated partial; thromboplastin time; CK: Creatine kinase, CK-MB: Creatine kinase-MB.

Table 2 Logistic regression analysis for risk odds of acute respiratory distress syndrome

Logistic univariate regression
Variables	OR (95%CI)	P value
Ages	1.05 (1.00-1.09)	0.017
Dyspnea	17.82 (4.62-68.71)	< 0.001
Dry/moist rales	9.06 (1.91-43.04)	0.006
Consolidative/mixed opacities	2.93 (1.34-6.38)	0.007
Lymphocyte	0.68 (0.01-0.43)	0.004
Creatine kinase	8.00 (2.02-31.72)	0.003
Creatine kinase-MB	/	0.255
D-dmier	1.41 (1.12-1.78)	0.004
Albumin	0.69 (0.59-0.82)	< 0.001
Alanine amino-transferase	1.03 (1.01-1.04)	0.001
Aspartate amino-transferase	1.02 (1.00-1.03)	0.048
Lactate dehydrogenase	1.02 (1.01-1.03)	< 0.001
C-reactive protein	1.04 (1.02-1.06)	0.001
Coexisting disease	3.94 (1.26-12.38)	0.019
Procalcitonin	17.10 (2.18-134.31)	0.007
Logistic multivariate regression
Variables	OR (95%CI)	P value
Dyspnea	26.89 (1.77-407.72)	0.018
Dry/moist rales	9.42 (1.02-87.08)	0.048
Lactate dehydrogenase	1.02 (1.00-1.03)	0.014

OR: Odds ratio.

Table 3 Comparison clinical characteristics of acute respiratory distress syndrome between Wuhan and outside Wuhan

Ref. (n)	Final follow-up date	ARDS rate (%)	ICU rate (%)	Death rate (%)	Still in hospital (%)	Median age (yr)	Dyspnea (%)	WBC (4-10 × 109/L) median, elevated rate	Lymphocyte (0.8-4 × 109/L) median, elevated rate	ALT (0-40 U/L) median, elevated rate
Chen et al[11], (99)	25 January	17	32	11	56	56	31	7.5, 24%	0.9, 35% (< 1.1)	39, 28% (> 50)
Huang et al[19], (41)	22 January	29	32	15	17	49	55	6.2, 30%	0.8, 63% (< 1.0)	32 /
Zhou et al[14], (191)	31 January	31	26	28.3	0	56	/	6.2, 21%	1.0, 40%	30, 31%
Wang et al[17], (138)	3 February	19.6	26.1	4.3	61.6	56	31.2	4.5, /	0.8, 70.3%	24 /
Wu et al[4], (201)	13 February	41.8	26.4	21.9	6.5	51	39.8	5.9, 23.4% (> 9.5)	0.9, 64.0% (< 1.1)	31, 21.7% (> 50)
Cao et al[12], (102)	15 February	19.6	17.6	16.7	0	54	/	/,/	0.9, 3.7% (< 1.1)	23, 24.8%
Total median/mean		26.3	26.7	16.2	23.5	53.7	39.5	6.2 (5.2-6.8)	0.9 (0.8-0.9)	31.0 (27.0-35.5)
Outside Wuhan
Guan et al[20], (1099)1	31 January	3.4	5	1.4	93.6	47	18.7	4.7, 5.9%	1.0, 83.2% (< 1.5)	/, 21.3%
Chen et al[16], (249)	25 February	3.2	8.8	0.8	12.8	51	7.6	4.7, 28.9%	1.1, 47.4%	23.0 /
Yang et al[13], (149)	15 February	0	0	0	51.0	45	1.34	4.6, 1.34%	1.2, 35.6% (< 1.1)	20, 12.1%
This study (197)	15 March	6.6	8.6	1.5	0	45	19.8	4.8, 2.0%	1.2, 23.9%	20, 16.2%
Total median/mean		3.3	5.6	0.9	21.3	47	11.9	4.7 (4.6-4.8)	1.2 (1.0-1.2)	20 (20-/)

¹A nationwide study.

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LDH: Lactate dehydrogenase; CRP: C-reactive protein; LPV/r: Lopinavir/ritonavir; WBC: White blood cell.

Table 4 Comparison clinical characteristics of acute respiratory distress syndrome between Wuhan and outside Wuhan

Ref. (n)	AST (0-40 U/L) median, elevated rate	D-dimer (0-0.5 mg/L) median, elevated rate	LDH (0-250 U/L) median, elevated rate	CRP (0-10 mg/L) median, elevated rate	CT bilateralpneumonia (%)	Antiviral rate (%)	Antibiotic rate (%)	Corticost-eroid rate (%)	Mechanical ventilation rate (%)
Chen et al[11], (99)	34, 35%	0.9, 36% (> 1.5)	336, 76%	51.3, 86% (> 5)	75	76 (oseltamivir)1	71	19	20
Huang et al[19], (41)	34, 37%	0.5, /	286, 73% (> 245)	/	98	93 (oseltamivir)	100	22	29
Zhou et al[14], (191)	/	0.8, 68%	300, 67% (> 245)	/	59	21 (LPV/r)	95	30	31
Wang et al[17], (138)	31, /	0.20, /	261, 39.9% (> 243)	/, /	/	89.9 (oseltamivir)	Many5	44.9	26
Wu et al[4], (201)	33, 29.8%	23.3% (> 1.5)	308, 98% (> 150)	42.4, 85.6% (> 5)	95	84.6 (oseltamivir)2	98	30.8	33
Cao et al[12], (102)	/, /	0.19, 20.8%	/, /	24.8, 51%	70.6	98.0 (oseltamivi)3	99	50	19.6
Total median/mean	33.5 (31.5-34.0)	0.65 (0.27-0.87)	300 (273-322)	42 (25-/)	83	77.1	92.6	32.8	26.4
Outside Wuhan
Guan et al[20], (1099)6	/, 22.2%	/, 46.4%	/, 41.0%	/, 60.7%	51.8	35.8 (oseltamivir)	58	18.6	6.10
Chen et al[16], (249)	25.0, /	/	229, /	12.0, 50%	81.5	Unknown (LPV/r, arbidol)	/	12.9	/
Yang et al[13], (149)	23, 18.2%	0.2, 14.1%	210, 30.2%	7.3, 55.0%	/	93.9 (interferon)	23	3.0	1.0
This study (197)	23, 12.2%	0.3, 26.4%	161, 12.7%	12.8, 53.3%	8.28	99.4 (arbidol, LPV/r)4	44	24.8	2.0
Total median/mean	23 (23-/)	0.25 (0.20-/)	210 (161-/)	12 (7.3-/)	72.3	76.4	41.5	14.9	3.0

¹Included ganciclovir, lopinavir and ritonavir.

²Oseltamivir (66.7%), ganciclovir (40.3%), LPV/r (14.1%), interferon (10.9%).

³Arbidol (34.3%), Oseltamivir (64.7%) and Lopinavir (27.5%).

⁴Arbidol, LPV/r, interferon-alpha, novaferon, and different combined regimens.

⁵Moxifloxacin (64.4%); ceftriaxone (24.6%); azithromycin (18.1%).

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LDH: Lactate dehydrogenase; CRP: C-reactive protein; LPV/r: Lopinavir/ritonavir; WBC: White blood cell.