The Effect of Noninvasive Ventilation Support on COVID-19 Patients and Risk Factors for Invasive Ventilation – A Retrospective and Multicenter Study

Figures & data

Table 1 Demographics and Clinical Variables Among COVID-19 Subjects

Variables	All (N=683)	No OT (N=315)	OT (N=300)	HFNOT or NIV (N=51)	IMV (N=17)	P^a
Age (IQR)	43 (33–55)	41 (30–50)^#&^	45 (34–64)*^&^	52 (43–64)*#^	66(54–80)*^#&	<0.001
Gender: Female (%)	332 (48.6)	158(50.2)	149 (49.7)	20 (39.2)	6 (35.3)	0.34
BMI (IQR)	23 (21–26)	23 (21–26)	24 (22–26)	23 (21–25)	23 (20–27)	0.55
Exposure
Contact with Wuhan (%)	533 (78.0)	257 (81.6)	230 (76.7)	35 (68.6)	11 (64.7)	0.26
Comorbidities, any (%)	221 (32.4)	74 (23.5)^#&^	106 (35.3)*^&^	29 (56.9)*^#	12 (70.6)*^#	<0.001
Diabetes (%)	61 (8.9)	22 (7.0)	28 (9.3)	9 (17.6)	2 (11.8)	0.09
Hypertension (%)	98 (14.3)	30 (9.5)^#&^	47 (15.7)*^&^	15 (29.4)*^#^	6 (35.3)*^#&	<0.001
Illness onset until hospitalization	4.0 (2–7)	3.0 (1–6)^#	3.0 (3–8)*	4.0 (3–8)	4.0 (1–7)	0.003
Shock (%)	7 (1.0)	0 (0)	0 (0)	2 (3.9)*^#	5 (29.4)*^#&	<0.001
Hospital days (IQR)	16 (11–23)	16 (11–22) ^^	15 (12–23) ^^	17 (12–27) ^^	26 (20–35)*^#&	<0.001
Day to recovery (IQR)	21 (16–28)	19 (15–25)^#&^	21(16–28)*^^	24 (17–31)*	29 (25–37)*^#	<0.001
Secondary bacterial infection (%)	38 (5.6)	7 (2.2)^&^	10 (3.3)^&^	11 (21.6)*^#^	10 (58.8)*^#&	<0.001
Antibiotics (%)	326 (47.7)	101 (32.1)^#&^	164 (54.6)*^&^	45 (88.2)*^#	16 (94.1)*^#	<0.001
Corticosteroids (%)	149 (21.8)	15 (4.8)^#&^	80 (26.7)*^&^	41 (80.4)*^#	13 (76.5)*^#	<0.001
Respiratory rate	20 (20–20)	20 (19–20)	20 (20–21)	20 (20–22)*#^	20 (20–20)	<0.001

Notes: ^aP value for statistical difference among the four groups (No OT, OT, HFNOT or NIV, and IMV). *Means statistic difference with No OT group, ^#Means statistic difference with OT group, ^&Means statistic difference with HFNOT or NIV group, ^{^}Means statistic difference with IMV group.

Abbreviations: COVID-19, coronavirus disease 2019; N, number of subjects; IQR, interquartile range; OT, oxygen therapy; HFNOT, high-flow nasal oxygen therapy; NIV, non-invasive ventilation; IMV, invasive mechanical ventilation.

Figure 1 The flow chart of the study. Of the 683 subjects, 315 (46.1%) did not receive OT, 300 (43.9%) had nasal oxygen therapy, 68 patients underwent HFNOT or NIV; among these 68 patients, 51 patients successfully recovered from hypoxia, 17 patients had to be intubated, and 4 patients died.

Table 2 Differences in Symptoms Among COVID-19 Patients without or with Different Kinds of Oxygen Therapy

Variables	All (N=683)	No OT (N=315)	OT (N=300)	HFNOT or NIV (N=51)	IMV (N=17)	P^a
Dry cough	440 (64.4)	206 (65.4) ^^	180 (60.0) ^&^	39 (76.5) ^#	15(88.2) *^#	0.02
Sputum production	169 (24.7)	92 (29.2) ^#	57 (19.0) *^^	12 (23.5)	8 (47.1) ^#	0.004
Dyspnea	101 (14.8)	31 (9.8) ^&^	38 (12.7) ^&^	21 (41.2) *^#	11 (64.7) *^#	<0.001
Runny nose	3 (0.4)	3 (1.0)	0 (0.0)	0 (0.0)	0 (0.0)	0.32
Sore throat	39 (5.7)	12 (3.8) ^#	27 (9.0) *^&	0 (0.0) ^#	0 (0.0)	0.007
Nasal congestion	15 (2.2)	13 (4.1) ^#	2 (0.7) *	0 (0.0)	0 (0.0)	0.02
Chest tightness	27 (4.0)	10 (3.2)	11 (3.7)	4 (7.8)	2 (11.8)	0.15
Palpitation	3 (0.4)	2 (0.6)	0 (0.0)	1 (2.0)	0 (0.0)	0.22
Hemoptysis	26 (3.8)	1 (0.3) ^#^	21 (7.0) *	1 (2.0) ^^	3 (17.6) *^&	<0.001
Fever	466 (68.2)	199 (63.2) ^&^	206 (68.7) ^&^	44 (86.3) *^#	17 (100) *^#	<0.001
Headache	51 (7.5)	21 (6.7) ^&	21 (7.0) ^&	8 (15.7) *^#	1 (5.9)	0.14
Fatigue	202 (29.6)	89 (28.3) ^^	80 (27.3) ^^	20 (39.2)	11 (64.7) * ^#	0.004
Myalgia	74 (10.8)	53 (16.8) ^#&	17 (5.7) *	3 (5.9) *	1 (5.9)	<0.001
Diarrhea	57 (8.3)	27 (8.6)	23 (7.7)	6 (11.8)	1 (5.9)	0.77
Nausea	33 (4.8)	8 (2.5) ^&^	17 (5.7)	6 (11.8) *	2 (11.8) *	0.01
Vomit	8 (1.2)	4 (1.3)	3 (1.0)	1 (2.0)	0 (0.0)	0.90

Notes: ^aP value for statistical difference among the four groups (No OT, OT, HFNOT or NIV, and IMV). *Means statistic difference with No OT group, ^#Means statistic difference with OT group, ^&Means statistic difference with HFNOT or NIV group, ^{^}Means statistic difference with IMV group.

Abbreviations: COVID-19, coronavirus disease 2019; N, number of subjects; IQR, interquartile range; OT, oxygen therapy; HFNOT, high-flow nasal oxygen therapy; NIV, non-invasive ventilation; IMV, invasive mechanical ventilation.

Table 3 Differences in Lab Findings Among COVID-19 Patients without or with Different Kinds of Oxygen Therapy

Variables	All (N=683)	No OT (N=315)	OT (N=300)	HFNOT or NIV (N=51)	IMV (N=17)	P^a
WBC	4.8 (3.7–6.2)	5.0 (3.9–6.3) ^^	4.6 (3.6–6.0) ^^	4.9 (4.1–6.0) ^^	6.7 (4.4–9.1) *^#&	0.009
Lym	1.2 (0.8–1.7)	1.3 (0.9–1.7) ^&	1.2 (0.9–1.6) ^&	0.8 (0.6–1.2) *^#	0.6 (0.4–0.9)	0.02
Neutrophil	3.0 (2.3–4.1)	3.1 (2.3–4.1) ^^	2.9 (2.1–3.8) ^^	3.6 (2.8–4.8)	5.2 (4.2–7.8) *^#	0.03
Platelets	196 (148–249)	219 (165–264) ^#&^	183 (143–240) *^^	185 (144–213) *^^	148 (124–165) *^#&	<0.001
Hb	133 (123–145)	135 (126–147) ^#	130 (120–143) *^&	133 (124–152) ^#^	131 (116–136) ^&	0.005
PT	12 (10–13)	12 (11–13) ^#	12 (11–13) *	12 (11–13)	12 (11–13)	0.002
APTT	32 (29–36)	32 (28–36)	33 (30–36)	32 (26–37)	32 (26–38)	0.44
ALT	21 (15–31)	21 (15–36) ^#	21 (15–28) *^&	28 (18–41) ^#	23 (19–33)	0.005
AST	24 (19–31)	23 (18–31) ^&	24 (19–31) ^&	44 (86.3) *^#	29 (22–45)	0.009
Albumin	40 (26–44)	42 (39–45) ^&^	39 (36–42)	35 (33–40) *	33 (29–37) *	0.04
Globulin	26 (23–29)	25 (19–30) ^#&^	26 (23–28) *^&	29 (27–31) *^#	27 (26–32) *	<0.001
CK	68 (46–108)	64 (45–98) ^&^	68 (46–106) ^&^	108 (54–195) *^#	168 (81–240) *^#	<0.001
Creatinine	63 (51–76)	65 (55–77) ^^	58 (45–72) ^^	65 (55–80)	67 (55–87) *^#	0.01
BUN	4.1 (3.2–5.1)	3.8 (3.1–4.6) ^&	4.3 (3.2–5.3) ^&	5.1 (3.8–8.1) *^#	6.5 (4.1–8.1)	<0.001
LDH	181 (147–224)	180 (154–221) ^&^	171 (141–211) ^&	241 (188–318) *^#	464 (305–511)	<0.001
Lactate	1.8 (1.2–2.6)	1.6 (1.0–2.3) ^#	2. 7 (1.9–3.1)*	1.84 (1.25–2.71)	2.20 (1.05–3.20)	0.02
PH	7.5 (7.4–7.5)	7.4 (7.4–7.5)	7.5 (7.4–7.5)	7.5 (7.4–7.5)	7.5 (7.4–7.5)	0.21
PaCO2	36.7 (32.9–41.1)	35.1 (28.7–37.7)	37.5 (33.0–41.4)	35.2 (29.6–38.7)	33.8 (27–88.9)	0.29
PaO2	84.8 (72.4–94.6)	94.1 (84.3–109)&^	83.4 (71.2–89.4) &	67.2 (48.8–82)*#^	75 (54–97) *	<0.001

Notes: ^aP value for statistical difference among the four groups (No OT, OT, HFNOT or NIV, and IMV). *Means statistic difference with No OT group, ^#Means statistic difference with OT group, ^&Means statistic difference with HFNOT or NIV group, ^{^}Means statistic difference with IMV group.

Abbreviations: COVID-19, coronavirus disease 2019; N, number of subjects; IQR, interquartile range; OT, oxygen therapy; HFNOT, High-flow nasal oxygen therapy; NIV, non-invasive ventilation; IMV, invasive mechanical ventilation; WBC, white blood cell; Lym, lymphocyte; Hb, hemoglobin; PT, Prothrombin Time; APTT, activated partial thromboplastin time; ALT; alanine aminotransferase; AST, aspartate aminotransferase; Ck, creatine kinase; BUN, blood urea nitrogen; LDH, Lactate dehydrogenase.

Table 4 The Effect of HFNOT or NIV on COVID-19 Patients with Respiratory Failure

Variables	Before HFNOT or NIV	After HFNOT or NIV	P
PH	7.4 (7.4–7.5)	7.4 (7.4–7.5)	0.55
PaO2 (mmHg)	61.9 (54.6–67.6)	88.9 (75.7–97.3)	<0.001
PaCO2 (mmHg)	35.0 (31.9–38.0)	37.7 (32.5–39.4)	0.05
SpO2(%)	93.0 (91.0–94.0)	97.2 (95.8–98.0)	<0.001
Oxygenation index	224.9 (213.6–244.8)	372.1 (337.1–428.8)	<0.001

Note: Oxygenation index = PaO2/FiO2.

Abbreviations: COVID-19, coronavirus disease 2019; HFNOT, high-flow nasal oxygen therapy; NIV, non-invasive ventilation; PaO2, partial artery pressure of oxygen; PaCO2, partial artery pressure of carbon dioxide; SpO2, oxygen saturation.

Table 5 Univariate and Stepwise Multivariate Analysis of Risk Factors for the Need of IMV

Variable	Univariate			Multivariate
	OR	95% CI	P	OR	95% CI	P
Age (years)	1.06	1.03–1.07	0.001	1.03	0.98–1.07	0.24
Hypertension	3.12	1.08–9.11	0.04	1.50	0.33–6.71	0.59
Bacterial infection	31.62	9.91–100.92	<0.001	6.87	1.63–29.02	0.009
Dry cough	3.88	0.86–17.47	0.07	–	–	–
Sputum production	4.70	1.62–13.41	0.004	2.53	0.64–10.03	0.19
Dyspnea	9.77	3.22–29.61	<0.001	2.79	0.59–13.14	0.20
Hemoptysis	3.76	0.99–14.32	0.05	–	–	–
Fever	5.86	1.79–19.2	0.09	–	–	–
Fatigue	4.85	1.62–14.55	0.005	2.74	0.74–10.19	0.13
White blood cell	1.17	1.03–1.32	0.02	1.19	0.52–2.70	0.68
Neutrophil	1.15	1.03–1.28	0.01	0.93	0.40–2.16	0.87
Platelets	0.99	0.98–1.00	0.004	0.99	0.97–1.00	0.08
Hemoglobin	0.98	0.95–1.01	0.15	–	–	–
Creatine kinase	1.00	1.00–1.01	0.001	1.00	1.00–1.01	0.22
Creatinine	1.01	1.00–1.01	0.05	–	–	–

Abbreviation: IMV, invasive mechanical ventilation.