Circulating Inflammatory Factor Levels in the Early Phase of COVID-19 are Associated with the Progression of Respiratory Failure: A Single-Center Retrospective Study

Figures & data

Table 1 Demographic Data of Patients in the Study

Variable	Total	Respiratory Failure		P-value
	(N=302)	YES (N=31)	NO (N=271)
Population, n (%)	302 (100%)	31 (10.3%)	271 (89.7%)	–
18–44 years	6 (2.0%)	0 (0%)	6 (2.2%)	0.360
45–60 years	48 (15.9%)	4 (12.9%)	44 (16.2%)
>60 years	248 (82.1%)	27 (87.1%)	221 (81.5%)
Age (years)	73.35±12.82	74.68±9.71	73.20±13.13	0.446
18–44 years	33.17±7.08	–	33.17±7.08	–
45–60 years	53.83±4.72	55.00±6.16	53.73±4.64	0.611
>60 years	78.10±7.68	77.59±6.01	78.17±7.87	0.714
Male, n (%)	191 (63.2%)	25 (80.6%)	166 (61.3%)	0.034*
18–44 years	5 (83.3%)	0 (0%)	5 (83.3%)	–
45–60 years	29 (60.4%)	4 (10.0%)	25 (56.8%)	0.142
>60 years	157 (63.3%)	21 (77.8%)	136 (61.5%)	0.138
Hypertension, n (%)	86 (28.5%)	7 (22.6%)	79 (29.2%)	0.443
18–44 years	1 (16.7%)	0 (0%)	1 (16.7%)	–
45–60 years	7 (14.6%)	1 (25.0%)	6 (13.6%)	0.480
>60 years	78 (31.5%)	6 (22.2%)	72 (32.6%)	0.380
Diabetes, n (%)	41 (13.6%)	3 (9.7%)	38 (14.0%)	0.695
18–44 years	0 (0%)	0 (0%)	0 (0%)	–
45–60 years	2 (4.2%)	0 (0%)	2 (4.5%)	0.839
>60 years	39 (15.7%)	3 (11.1%)	36 (16.3%)	0.779
Coronary heart disease, n (%)	6 (2.0%)	0 (0%)	6 (2.2%)	0.875
18–44 years	0 (0%)	0 (0%)	0 (0%)	–
45–60 years	0 (0%)	0 (0%)	0 (0%)	–
>60 years	6 (2.4%)	0 (0%)	6 (2.7%)	0.497
Stroke, n (%)	26 (8.6%)	3 (9.7%)	23 (8.5%)	0.739
18–44 years	1 (16.7%)	0 (0%)	1 (16.7%)	–
45–60 years	1 (2.1%)	0 (0%)	1 (2.3%)	0.480
>60 years	24 (9.7%)	3 (11.1%)	21 (9.5%)	0.192

Notes: *P<0.05, significant difference.

Table 2 Laboratory Findings of Study Patients

Variable	Total	Respiratory Failure		P-value
	(N=302)	YES (N=31)	NO (N=271)
Oxygen partial pressure (mmHg)	85.01±34.43	70.54±24.82	87.09±35.17	0.007*
≤60 years	84.69±29.91	59.55±2.47	87.97±30.31	<0.0001*
>60 years	85.06±35.17	72.11±26.21	86.94±35.98	0.028*
Oxygen saturation (%)	93.50±8.42	91.89±5.20	93.74±8.77	0.315
≤60 years	91.92±16.03	93.10±1.21	91.77±17.08	0.895
>60 years	93.75±6.51	91.71±5.54	94.05±6.61	0.125
Calcium (mmol/L)	2.07±0.21	1.99±0.13	2.07±0.22	0.172
≤60 years	2.10±0.37	1.94±0.10	2.11±0.38	0.540
>60 years	2.06±0.14	2.01±0.13	2.06±0.14	0.150
Magnesium (mmol/L)	0.89±0.16	0.87±0.24	0.90±0.15	0.620
≤60 years	0.91±0.12	0.78±0.11	0.93±0.11	0.296
>60 years	0.89±0.18	0.88±0.25	0.89±0.16	0.852
Thyrocalcitonin (mmol/L)	0.10 (0, 0.20)	0.30 (0.10, 0.95)	0.10 (0, 0.20)	<0.0001*
≤60 years	0(0, 0.10)	0.60 (0.3, 0.81)	0 (0, 0.10)	0.023*
>60 years	0.10 (0.10, 0.20)	0.20 (0.1,0.80)	0.10 (0,0.20)	0.001*
Ferritin (mmol/L)	766.25±498.80	765.74±465.80	766.29±502.88	0.997
≤60 years	794.28±583.05	740.00±441.71	804.43±591.13	0.628
>60 years	761.07±483.60	784.01±477.78	758.82±485.76	0.853
Lactic acid (mmol/L)	2.05±1.16	2.49±1.15	1.99±1.15	0.048*
≤60 years	1.88±0.69	2.64±1.22	1.77±0.55	0.037*
>60 years	2.08±1.21	2.46±1.17	2.02±1.21	0.117
C-reactive protein (mmol/L)	36.40 (11.50, 82.60)	55.30 (14.60, 93.70)	35.45 (11.20, 79.80)	0.224
≤60 years	19.10 (3.80, 47.75)	89.80 (20.50, 168.78)	17.10 (3.50, 43.15)	0.047*
>60 years	42.35 (14.68, 89.68)	47.10 (14.60,83.30)	42.20 (14.70, 89.90)	0.813
D-dimer (mg/L)	0.47 (0.22, 1.20)	1.17 (0.38, 3.24)	0.43 (0.21, 1.10)	<0.0001*
≤60 years	0.22 (0.15, 0.42)	0.43 (0.26,2.35)	0.21 (0.14,0.37)	0.029*
>60 years	0.58 (0.26, 1.46)	1.41 (0.37,7.08)	0.54 (0.25,1.27)	0.003*
Erythrocyte distribution width (%)	13.43±2.07	13.60±1.04	13.41±2.15	0.630
≤60 years	13.23±1.82	14.00±0.45	13.17±1.87	0.382
>60 years	13.47±2.12	13.54±1.09	13.46±2.22	0.866
White blood cell (×10^9/L)	7.31±4.52	9.34±5.80	7.07±4.29	0.043*
≤60 years	6.93±4.10	6.05±3.40	7.00±4.18	0.660
>60 years	7.40±4.61	9.82±5.96	7.09±4.33	0.004*
Neutrophil (×10^9/L)	6.02±4.36	8.28±5.76	5.76±4.10	0.024*
≤60 years	5.35±3.83	5.40±3.69	5.35±3.88	0.979
>60 years	6.17±4.47	8.70±5.94	5.86±4.15	0.002*
Lymphocyte (×10^9/L)	0.85±0.53	0.64±0.34	0.87±0.54	0.022*
≤60 years	1.12±0.59	0.48±0.38	1.17±0.58	0.022*
>60 years	0.79±0.50	0.67±0.33	0.80±0.51	0.067
Monocyte (×10^9/L)	0.42±0.36	0.37±0.21	0.43±0.37	0.350
≤60 years	0.52±0.54	0.18±0.05	0.55±0.55	0.188
>60 years	0.40±0.29	0.39±0.21	0.40±0.30	0.904
Platelet volume distribution width (%)	16.09±1.47	16.65±0.70	16.02±1.52	0.023*
≤60 years	15.59±1.98	16.70±0.67	15.50±2.03	0.247
>60 years	16.20±1.31	16.65±0.71	16.15±1.36	0.004*

Notes: *P<0.05, significant difference.

Table 3 Immunoinflammatory Biomarker Levels of Study Patients

Variable	Total	Respiratory Failure		Z-value	P-value
	(N=302)	YES (N=31)	NO (N=271)
IL-2 (pg/mL)	0.29 (0, 0.50)	0.32 (0, 0.68)	0.27 (0, 0.50)	−0.902	0.367
≤60 years	0.30 (0, 0.54)	0.57 (0.08, 1.02)	0.29 (0,0.50)	−0.920	0.357
>60 years	0.27 (0,0.50)	0.32 (0,0.66)	0.01 (0, 0.50)	−0.661	0.508
IL-4 (pg/mL)	0 (0, 0.85)	0 (0, 0.54)	0 (0, 0)	−2.029	0.042*
≤60 years	0 (0,0.54)	0.75 (0.14, 0.96)	0 (0,0.54)	−1.813	0.070
>60 years	0 (0, 0)	0 (0,0.54)	0 (0, 0)	−1.579	0.114
IL-6 (pg/mL)	14.31 (4.45, 49.62)	40.76 (12.33, 90.28)	12.58 (4.06, 45.29)	−3.568	<0.0001*
≤60 years	8.24 (2.53, 38.00)	71.07 (20.37, 271.77)	7.89 (2.25, 33.14)	−2.345	0.019*
>60 years	16.57 (5.23, 57.07)	37.60 (12.33, 81.42)	16.02 (4.46, 49.58)	−2.802	0.005*
IL-10 (pg/mL)	4.75 (2.61, 8.64)	6.65 (4.12, 11.34)	4.33 (2.47, 8.20)	−2.517	0.012*
≤60 years	4.24 (2.77, 8.64)	6.92 (2.72, 10.70)	4.07 (2.77, 8.20)	−0.628	0.530
>60 years	4.75 (2.60, 8.71)	6.65 (4.12, 14.01)	4.54 (2.47, 8.24)	−2.507	0.012*
IL-17 (pg/mL)	6.27 (0, 10.05)	9.48 (4.31, 12.13)	6.27 (0, 9.67)	−2.099	0.036*
≤60 years	6.64 (0,10.56)	11.35 (10.56, 14.97)	5.99 (0, 9.61)	−2.282	0.023*
>60 years	6.27 (0,9.918)	8.05 (2.20, 11.93)	6.27 (0, 9.67)	−1.284	0.199
IFN-γ (pg/mL)	0.56 (0, 1.31)	0.56 (0, 1.62)	0.56 (0, 1.29)	−0.863	0.388
≤60 years	0.60 (0.24,1.36)	1.09 (0.41,3.68)	0.58 (0.22,1.36)	−0.994	0.320
>60 years	0.56 (0,1.29)	0.55 (0,1.62)	0.56 (0, 1.27)	−0.579	0.563
TNF-α (pg/mL)	0 (0, 0.50)	0 (0, 0.71)	0 (0, 0.50)	−0.769	0.442
≤60 years	0.22 (0,0.73)	0.25 (0,0.66)	0.22 (0, 0.77)	−0.158	0.875
>60 years	0 (0, 0.50)	0 (0,0.71)	0 (0,0.50)	−0.992	0.321

Note: *P<0.05, significant difference.

Table 4 Clinical Parameters and Immunoinflammatory Biomarkers Correlated with Respiratory Failure

Variable	R	P-value
Age	0.017	0.767
Sex	0.122	0.034*
Oxygen partial pressure	−0.208	0.004*
Oxygen saturation	−0.220	0.002*
Lactic acid	0.193	0.007*
C-reactive protein	0.071	0.224
White Blood Cell	0.121	0.038*
Neutrophil	0.137	0.019*
Lymphocyte	−0.129	0.026*
Monocyte	−0.045	0.438
Erythrocyte distribution width	0.131	0.024*
Platelet Volume Distribution Width	0.160	0.006*
Thyrocalcitonin	0.280	<0.0001*
Erythrocyte Sedimentation	0.035	0.674
Ferritin	0.017	0.817
D-dimer	0.214	<0.0001*
Calcium	−0.152	0.042*
Magnesium	−0.054	0.609
IL-2	0.052	0.368
IL-4	0.117	0.042*
IL-6	0.206	<0.0001*
IL-10	0.145	0.012*
IL-17	0.121	0.036*
IFN-γ	0.050	0.389
TNF-α	0.044	0.443

Note: *P<0.05, significant difference.

Table 5 Predictive Value of the Serum Immunoinflammatory Biomarker Levels for the Occurrence of Respiratory Failure

Variables	AUC (95% CI)	Youden Index	Sensitivity	Specificity	P-value
IL-2	0.552 (0.430–0.674)	0.145	0.621	0.525	0.3926
IL-4	0.585 (0.459–0.711)	0.180	0.414	0.766	0.1576
IL-6	0.650 (0.555–0.745)	0.398	0.931	0.467	0.0133*
IL-10	0.624 (0.509–0.739)	0.307	0.828	0.480	0.0403*
IL-17	0.634 (0.519–0.749)	0.586	0.639	0.226	0.0263*
IFN-γ	0.527 (0.405–0.650)	0.136	0.387	0.749	0.6521
TNF-α	0.546 (0.428–0.665)	0.084	0.290	0.793	0.4455
Total	0.806 (0.718–0.895)	0.477	0.609	0.868	<0.0001*

Note: *P<0.05, significant difference.

Figure 1 Prediction value of serum immunoinflammatory biomarker levels for respiratory failure in patients with COVID-19.

Figure 2 Study population flowchart. The final study cohort comprised 302 patients.