We enrolled 54 severe COVID-19 patients treated with HFNC (Fig. 1). Twenty-eight cases (51.9%, 28/54) were successfully treated by HFNC (Success group); 26 cases (48.1%, 26/54) experienced HFNC treatment failure (Failure group). Among patients in the Failure group, 9 cases received noninvasive ventilation as rescue therapy, and 15 cases received endotracheal intubation and invasive mechanical ventilation as rescue therapy. In addition, among 9 cases receiving noninvasive ventilation, 6 cases received endotracheal intubation and invasive mechanical ventilation as rescue therapy. Among 10 cases that died in the Failure group, 2 COVID-19 cases with a long time of coronary heart disease died during HFNC therapy because of sudden cardiac arrest induced by the initial rhythm of ventricular fibrillation, 6 cases died during invasive mechanical ventilation therapy because of severe ARDS, and 2 cases died during noninvasive ventilation therapy because of the relative’s refusal to early intubation and invasive mechanical ventilation.
The clinical characteristics of severe COVID-19 patients treated with HFNC in the Success and Failure groups are summarized in Table 1. Patients in the Failure group were older than those in the Success group, but without significant difference; whereas the percentage of patients older than 60 years of age in the Failure group was higher than that in the Success group (69.2% vs. 30.8%, respectively; P = 0.001). Male patients were more common in the Failure group, with a higher proportion than that in the Success group (61.5% vs. 38.5%, respectively; P < 0.001). Notably, patients in the Failure group had a significantly higher percentage of fatigue, anorexia, and the comorbidity of cardiovascular disease than patients in the Success group. In addition, the time from onset to diagnosis was longer in the Failure group than that in the Success group, indicating delayed hospitalization and treatment in the Failure group. Body temperature, respiratory rate, and heart rate were also significantly higher in the Failure group than in the Success group. Furthermore, patients in the Failure group had significantly higher SOFA scores, with a significantly higher percentage of ARDS, septic shock, and acute myocardial and kidney injury than those in the Success group, indicating greater disease severity in the patients in the Failure group. Patients in the Failure group had significantly higher neutrophil counts, prothrombin time, creatinine level and C-reactive protein, a significantly lower PaO2 / FiO2 than the Success group (all P<0.05).
Table 1 Characteristics of severe COVID-19 patients treated with HFNC
|
Normal range
|
Total
|
Success group
|
Failure group
|
x2/F
|
P*
|
|
|
(n = 54)
|
(n = 28)
|
(n = 26)
|
|
Age (years)
|
—
|
64 (27- 95)
|
57 (27-87)
|
74 (34-95)
|
1.951
|
0.057
|
<60 [n (%)]
|
—
|
23 (42.6)
|
15 (53.6)
|
8 (30.8)
|
10.824
|
0.001
|
≥60 [n (%)]
|
—
|
31 (57.3)
|
13 (46.4)
|
18 (69.2)
|
10.824
|
0.001
|
Male [n (%)]
|
—
|
25 (46.3)
|
9 (32.1)
|
16 (61.5)
|
18.602
|
< 0.001
|
Source of infection [n (%)]
|
|
|
|
|
|
|
No
|
—
|
44 (81.5)
|
23 (82.1)
|
20 (77.0)
|
116.114
|
< 0.001
|
Family gathering
|
—
|
6 (11.1)
|
3 (10.7)
|
3 (11.5)
|
116.114
|
< 0.001
|
Hospital contacting
|
—
|
4 (7.4)
|
2 (7.1)
|
3 (11.5)
|
116.114
|
< 0.001
|
Signs and symptoms [n (%)]
|
|
|
|
|
|
|
Fever
|
—
|
20 (30.0)
|
13 (46.4)
|
7 (26.9)
|
2.200
|
0.138
|
Dyspnea
|
—
|
36 (66.7)
|
18 (64.3)
|
18 (69.2)
|
0.561
|
0.454
|
Dry cough
|
—
|
26 (48.1)
|
15 (53.6)
|
11(42.3)
|
0.685
|
0.408
|
Fatigue
|
—
|
28 (51.9)
|
10 (35.7)
|
18 (69.2)
|
8.026
|
0.005
|
Anorexia
|
—
|
19 (35.2)
|
6 (21.4)
|
13 (50.0)
|
4.826
|
0.028
|
Dizzy
|
—
|
1 (1.9)
|
0 (0)
|
1 (3.8)
|
1.097
|
0.295
|
Diarrhea
|
—
|
1 (1.9)
|
1 (3.6)
|
0 (0)
|
0.946
|
0.331
|
Comorbidities [n (%)]
|
|
|
|
|
|
|
Hypertension
|
—
|
21 (38.9)
|
9 (32.1)
|
12 (46.2)
|
1.114
|
0.291
|
Diabetes
|
—
|
10 (18.5)
|
7 (25.0)
|
3 (11.5)
|
1.619
|
0.203
|
Cardiovascular disease
|
—
|
11 (20.4)
|
2 (7.1)
|
9 (34.6)
|
6.273
|
0.012
|
Cerebrovascular disease
|
—
|
4 (7.4)
|
1 (3.6)
|
3 (11.5)
|
1.248
|
0.264
|
Chronic kidney injury
|
—
|
2 (3.7)
|
1 (3.6)
|
1 (3.8)
|
0.003
|
0.957
|
COPD
|
—
|
6 (11.1)
|
3 (10.7)
|
3 (11.5)
|
0.009
|
0.923
|
Cancer
|
—
|
1 (1.9)
|
0 (0)
|
1 (3.8)
|
1.097
|
0.295
|
Hyperthyroidism
|
—
|
1 (1.9)
|
0 (0)
|
1 (3.8)
|
1.097
|
0.295
|
Time from onset to diagnosis (days)
|
—
|
4 (0-9)
|
3 (0-9)
|
5 (1-9)
|
19.505
|
0.021
|
SOFA (scores)
|
—
|
3.0 (0-14)
|
2.5 (0-5)
|
5.0 (2-14)
|
4.186
|
< 0.001
|
Vital signs
|
|
|
|
|
|
|
Temperature (℃)
|
36-37
|
37.5 (35.5-39.2)
|
37.4 (36.0-39.2)
|
37.7 (35.5-39.0)
|
2.064
|
0.031
|
Respiratory rate (/min)
|
12-20
|
28 (16-40)
|
25(16-32)
|
31 (16-40)
|
1.688
|
0.042
|
Heart rate (/min)
|
60-90
|
88 (55-146)
|
87 (55-130)
|
98 (70-146)
|
1.429
|
0.027
|
MAP (mmHg)
|
70-105
|
93 (75-123)
|
94 (75-123)
|
93 (77-123)
|
1.892
|
0.062
|
Organ function injury [n (%)]
|
|
|
|
|
|
|
ARDS
|
—
|
32 (59.3)
|
11 (39.3)
|
21 (80.8)
|
9.610
|
0.002
|
Septic shock
|
—
|
8 (14.8)
|
0 (0)
|
8 (30.8)
|
10.114
|
0.001
|
Myocardial damage
|
—
|
11 (20.4)
|
1 (3.6)
|
10 (38.5)
|
10.117
|
0.001
|
Liver injury
|
—
|
16 (29.6)
|
7 (25.0)
|
9 (34.6)
|
0.598
|
0.439
|
AKI
|
—
|
8 (14.8)
|
0 (0)
|
8 (30.8)
|
10.114
|
0.001
|
Gastrointestinal hemorrhage
|
—
|
1 (1.9)
|
0 (0)
|
1 (3.8)
|
1.058
|
0.304
|
Whole blood cell analysis
|
|
|
|
|
|
|
White blood cells (×109/L)
|
3.5-9.5
|
7.01 (2.01-21.03)
|
5.62 (2.01-14.02)
|
8.85 (3.02-21.03)
|
21.430
|
0.065
|
Neutrophils count (×109/L)
|
1.8-6.3
|
5.51 (2.02-20.14)
|
3.61 (2.02-13.25)
|
7.57 (2.03-20.27)
|
17.850
|
0.013
|
Lymphocytes (×109/L)
|
1.1-3.2
|
0.87 (0-2.02)
|
1.01 (0-2.02)
|
0.79 (0-2.02)
|
5.582
|
0.061
|
Red blood cells (×1012/L)
|
3.8-5.1
|
4.12 (3.02-5.02)
|
4.11 (3.03-5.03)
|
4.13 (3.22-4.91)
|
2.407
|
0.492
|
Hemoglobin (g/L)
|
115-150
|
128 (72-157)
|
128 (72-157)
|
128 (104-157)
|
36.947
|
0.334
|
Platelets (×109/L)
|
125-350
|
176 (20-396)
|
205 (59-396)
|
149 (20-326)
|
50.072
|
0.391
|
Coagulation function parameters
|
|
|
|
|
|
|
Prothrombin time (seconds)
|
9-13
|
12.4 (10.5-20.2)
|
12.0 (10.5-15.3)
|
13.5 (10.8-20.2)
|
17.069
|
0.009
|
APTT (seconds)
|
25.0-31.3
|
28.8 (22.7-63.2)
|
28.3 (22.7-55.8)
|
29 (23.9-63.2)
|
15.638
|
0.269
|
Fibrinogen (g/L)
|
2-4
|
4.50 (0.28-7.45)
|
4.56 (2.48-7.45)
|
3.72 (0.28-6.78)
|
12.610
|
0.082
|
D-dimer (mg/L)
|
0-0.55
|
1.3 (0.2-179.7)
|
0.9 (0.2-13.5)
|
10.0 (0.3-179.7)
|
21.082
|
0.275
|
Liver injury markers
|
|
|
|
|
|
|
ALT (U/L)
|
9-50
|
25.1 (7.3-532.6)
|
22.1 (7.3-532.6)
|
27.2 (8.9-102.2)
|
37.144
|
0.326
|
AST(U/L)
|
15-40
|
33.3 (13.5-768.0)
|
25.2 (13.0-768.5)
|
43.2 (21.5-139.5)
|
44.148
|
0.195
|
Albumin (g/L)
|
40-55
|
34.0 (27.9-61.1)
|
35.2 (27.9-61.1)
|
33.4 (27.9-40.6)
|
15.606
|
0.481
|
Total bilirubin (μmol/L)
|
0-23
|
10.0 (6.1-411.3)
|
9.7 (6.1-21.3)
|
12.4 (7.5-411.3)
|
17.222
|
0.371
|
Kidney injury marker
|
|
|
|
|
|
|
Creatinine (μmol/L)
|
59-104
|
67 (13-293)
|
64 (42-139)
|
75 (13-293)
|
2.482
|
0.027
|
BUN (mmol/L)
|
3.6-9.5
|
5.7 (2.0-31.5)
|
4.9 (2.0-14.6)
|
7.4 (2.9-31.5)
|
1.877
|
0.175
|
Blood gas analysis
|
|
|
|
|
|
|
PH
|
7.35-7.45
|
7.43 (7.72-7.14)
|
7.43 (7.33-7.54)
|
7.43 (7.14-7.72)
|
1.603
|
0.112
|
PaCO2 (mmHg)
|
35-48
|
37 (25-68)
|
36 (25-53)
|
34 (25-68)
|
1.683
|
0.090
|
PaO2/FiO2 (mmHg)
|
400-500
|
186 (49-475)
|
223 (98-475)
|
143 (49-273)
|
10.385
|
0.032
|
C-reactive protein (mg/L)
|
0-10
|
61.3 (5.2-200.0)
|
52.6 (5.5-200.0)
|
102.3 (5.0-200.0)
|
7.975
|
0.007
|
PCT (ng/mL)
|
0-0.1
|
0.12 (0.01-2.96)
|
0.11 (0.02-2.96)
|
0.17 (0.01-2.01)
|
1.323
|
0.516
|
|
|
|
|
|
|
|
|
|
Note: Values are the medians (ranges). P* indicates the P-values for the comparisons of the Success group and Failure group. x2/F, chi-square/Fisher’s exact test; HFNC, high-flow nasal cannula; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; SOFA, sequential organ failure assessment; MAP, mean arterial pressure; ARDS, acute respiratory distress syndrome; AKI, acute kidney injury; PCT, procalcitonin; PaO2/FiO2, arterial partial pressure of oxygen/fraction of inspired oxygen; PaCO2, arterial partial pressure of carbon dioxide; BUN, blood urea nitrogen; APTT, activated partial thromboplastin time; ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Considering the small sample size in our study (n = 54) and to avoid overfitting in the model, we chose five independent variables for binary logistic regression analysis according to previous findings and clinical constraints. We used HFNC failure as a dependent variable, and age, sex, time from onset to diagnosis, PaO2/FiO2, and SOFA scores as independent variables. Binary logistic regression analysis showed that only male, low PaO2/FiO2 and SOFA scores were independent risk factors significantly associated with HFNC failure in patients with severe COVID-19 (Table 2).
Table 2 Risk factors associated with HFNC failure in severe COVID-19 patients
|
β value
|
Wald value
|
P value
|
OR value
|
95% CI
|
Age
|
0.005
|
0.024
|
0.877
|
1.005
|
0.948-1.064
|
Male
|
1.821
|
4.880
|
0.027
|
6.178
|
1.228-31.089
|
Time from onset to diagnosis
|
0.057
|
0.111
|
0.739
|
1.058
|
0.758-1.477
|
PaO2/FiO2
|
-0.019
|
4.995
|
0.025
|
0.981
|
0.965-0.998
|
SOFA scores
|
0.790
|
4.288
|
0.038
|
2.202
|
1.043-4.650
|
Constant
|
0.158
|
0.003
|
0.954
|
1.171
|
|
Note: CI, confidence interval; COVID-19, coronavirus disease 2019; HFNC, high-flow nasal cannula; OR, odds ratio; PaO2/FiO2, arterial partial pressure of oxygen/fraction of inspired oxygen; SOFA, sequential organ failure assessment.