Association of carbon monoxide poisonings and carboxyhemoglobin levels with COVID-19 and clinical severity

Table 1 Basal and laboratory findings of the patients

			Disease periods
		All patients (n = 479), mean ± SD	Pre-pandemic, (n = 253), mean ± SD	Pandemic (n = 226)				P value
				Non-COVID-19 (n = 83), mean ± SD	Mild COVID-19 (n = 60), mean ± SD	Moderate COVID-19 (n = 45), mean ± SD	Severe COVID-19 (n = 38), mean ± SD
Baseline characteristics
Age (year)		54.93 ± 11.51	50.56 ± 11.24	56.87 ± 10.29	57.32 ± 9.58	65.98 ± 6.70	62.87 ± 7.50	< 0.001
Gender	Female	187 (39)	98 (38.7)	38 (45.8)	24 (40)	16 (35.6)	11 (28.9)	0.3461
	Male	292 (61)	155 (61.3)	45 (54.2)	36 (60)	29 (64.4)	27 (71.1)
Exposure time (h)		4.31 ± 1.74	4.09 ± 1.86	4.84 ± 1.98	4.25 ± 1.26	4.69 ± 1.24	4.24 ± 1.23	0.201
Laboratory findings
Arterial blood gas	pH (7.35-7.45)	7.28 ± 0.15	7.35 ± 0.10	7.29 ± 0.12	7.23 ± 0.12	7.14 ± 0.16	7.05 ± 0.16	< 0.001
	PaCO2 (mmHg) (32-45)	47.07 ± 8.34	43.32 ± 6.81	46.04 ± 7.90	51.10 ± 6.34	55.67 ± 4.93	57.76 ± 4.49	< 0.001
	PaO2 (mmHg) (80-100)	86.92 ± 8.01	89.63 ± 7.62	87.10 ± 6.44	83.01 ± 7.40	82.81 ± 6.50	79.50 ± 7.18	< 0.001
	K+ (mmol/L) (3.4-4.5)	4.20 ± 0.71	4.00 ± 0.58	4.01 ± 0.55	4.34 ± 0.78	4.64 ± 0.64	5.25 ± 0.63	< 0.001
	Na+ (mmol/L) (135-149)	138.04 ± 4.52	138.52 ± 4.70	137.35 ± 4.33	137.98 ± 4.22	17.13 ± 4.23	137.48 ± 4.33	0.239
	Ca++ (mmol/L) (1.15-.29)	1.16 ± 0.26	1.18 ± 0.25	1.19 ± 0.26	1.11 ± 0.20	1.07 ± 0.29	1.06 ± 0.37	0.02
	Cl- (mmol/L) (98-106)	99.90 ± 8.27	99.97 ± 7.14	100.01 ± 5.72	100.01 ± 12.69	99.98 ± 10.19	98.92 ± 9.05	0.944
	BS (mg/Dl) (70-105)	129.59 ± 24.66	120.49 ± 20.98	129.35 ± 21.89	132.75 ± 24.18	155.91 ± 21.58	154.50 ± 15.73	< 0.001
	HCO3 (mmol/L) (22-26)	17.68 ± 6.18	20.31 ± 5.46	17.91 ± 5.49	15.13 ± 4.59	12.47 ± 4.62	9.92 ± 3.73	< 0.001
	BE (mmol/L) (-3.0-3.0)	7.09 ± 5.56	4.76 ± 4.68	6.76 ± 4.85	9.22 ± 4.43	11.79 ± 4.48	14.41 ± 3.58	< 0.001
	Lactate (mmol/L) (0.5-1.6)	2.85 ± 1.99	1.89 ± 1.24	2.60 ± 1.57	3.54 ± 1.44	4.87 ± 1.92	6.33 ± 1.76	< 0.001
	COHb (%) (0.5-1.5)	29.68 ± 7.85	26.19 ± 6.68	27.63 ± 5.37	34.25 ± 5.00	37.35 ± 5.38	41.08 ± 7.55	< 0.001
Troponin I (ng/mL) (0.0-0.05)		0.40 ± 1.91	0.11 ± 0.25	0.20 ± 0.28	0.42 ± 0.35	0.82 ± 0.31	1.09 ± 0.50	< 0.001

¹Chi-Square test.

Other P values were calculated by the Kruskal-Wallis H test. Bold values indicate significance at P < 0.05. SD: Standard Deviation; COVID-19: Coronavirus disease 2019; pH: Potential of Hydrogen; PaCO₂: Partial pressure of carbon dioxide; PaO₂: Partial arterial oxygen pressure; K⁺: Potassium; Na⁺: Sodium; Ca⁺⁺: Calcium; Cl^-: Chloride; BS: Blood sugar; HCO₃: Bicarbonate; BE: Base Excess; COHb: Carboxyhemoglobin.

Table 2 Analysis of patient survival, baseline values and variables (mean ± SD)

Survival			Outpatient (n = 258)	Hospitalization (n = 117)	ICU (n = 69)	Mortality (n = 35)	P value
Baseline characteristics
Age (yr)			50.27 ± 10.67	47.76 ± 11.05	61.61 ± 7.56		< 0.001
Gender		Female	107 (41.5)	47 (40.2)	21 (30.4)	12 (34.3)	0.1281
		Male	151 (58.5)	70 (59.8)	48 (69.6)	23 (65.7)
Exposure time (h)			3.90 ± 1.62	4.45 ± 1.68	5.19 ± 1.79	5.14 ± 1.78	< 0.001
COHb (%)			23.98 ± 4.19	3238 ± 2.81	38.49 ± 2.99	45.26 ± 3.19	< 0.001
Troponin I (ng/mL)			0.04 ± 0.09	0.33 ± 0.27	0.77 ± 0.21	1.35 ± 0.36	< 0.001
Lactate (mmol/L)			1.42 ± 0.39	3.54 ± 0.95	4.34 ± 0.68	8.14 ± 0.63	< 0.001
Patient groups	Pre-pandemic		198 (76.7)	40 (34.2)	10 (14.5)	5 (14.3)	< 0.0011
	Pandemic	Non-COVID-19	50 (19.4)	26 (22.2)	5 (7.2)	2 (5.7)
		Mild	8 (3.1)	28 (23.9)	21 (30.4)	3 (8.6)
		Moderate	2 (0.8)	16 (13.7)	17 (24.6)	10 (28.6)
		Severe	0	7 (6)	16 (23.2)	15 (42.9)

¹Chi-Square test.

Other P values were calculated by the Kruskal-Wallis H test. Bold values indicate significance at P < 0.05. SD: Standard deviation; COVID-19: Coronavirus disease 2019; ICU: Intensive care unit; COHb: Carboxyhemoglobin.

Table 3 Univariate and multivariate analysis of variables in patient groups

Patient groups	Univariate				Multivariate
	R square	β	t	P value	R square	β	t		P value
COHb (%)	0.452	0.672	19.837	< 0.001	0.589	0.166	2.287		0.023
Troponin (ng/mL)	0.485	0.696	21.197	< 0.001		0.258	3.457		0.001
Lactate (mmol/L)	0.468	0.684	20.501	< 0.001		0.241	2.462		0.014
PaCO2 (mmHg)	0.364	0.604	16.535	< 0.001		0.338	6.040		< 0.001
Bicarbonate (mmol/L)	0.309	-0.556	-14.659	< 0.001		0.259	2.306		0.022
Calcium (mmol/L)	0.028	-0.168	-3.723	< 0.001		0.072	2.141		0.033
Glucose (mg/dL)	0.243	0.494	12.420	< 0.001		0.166	3.532		< 0.001
Age (year)	0.187	0.433	10.483	< 0.001
pH	0.386	-0.621	-17.319	< 0.001
PaO2 (mmHg)	0.178	-0.422	-10.164	< 0.001
Potassium (mmol/L)	0.233	0.482	12.031	< 0.001
Sodium (mmol/L)	0.009	-0.095	-2.083	0.038
Base excess (mmol/L)	0.317	0.563	14.480	< 0.001

Bold values indicate significance at P < 0.05. COHb: Carboxyhemoglobin; PaCO₂: Partial pressure of carbon dioxide; pH: Potential of hydrogen; PaO₂: Partial arterial oxygen pressure.

Table 4 Receiver operating characteristic curve of mortality

	Sensitivity (%)	Specificity (%)	AUC	95%CI	P value
COHb (%)	98.4	97.1	0.989	0.980-0.999	< 0.001
Troponin (ng/mL)	98.6	97.8	0.996	0.993-1.000	< 0.001
Lactate (mmol/L)	99.5	98.9	1.000	1.000-1.000	< 0.001

COHb: Carboxyhemoglobin; AUC: Area under the curve; CI: Confidence interval.

Table 5 Spearman’s rho correlation analysis of variables in patient and survival groups

Spearman’s rho	Patients		Survival
	R	P value	R	P value
Age (year)	0.441	< 0.001	0.480	< 0.001
Exposure time (hour)	0.148	< 0.001	0.290	< 0.001
COHb (%)	0.609	< 0.001	0.873	< 0.001
Troponin (ng/mL)	0.608	< 0.001	0.807	< 0.001
Lactate (mmol/L)	0.643	< 0.001	0.880	< 0.001
pH	-0.595	< 0.001	-0.857	< 0.001
PaCO2 (mmHg)	0.571	< 0.001	0.801	< 0.001
PaO2 (mmHg)	-0.495	< 0.001	-0.747	< 0.001
Glucose (mg/dL)	0.467	< 0.001	0.432	< 0.001
Bicarbonate (mmol/L)	-0.536	< 0.001	-0.834	< 0.001
Base excess (mmol/L)	0.541	< 0.001	0.839	< 0.001

COHb: Carboxyhemoglobin; pH: Potential of hydrogen; PaCO₂: Partial pressure of carbon dioxide; PaO₂: Partial arterial oxygen pressure.