Can Hematological Ratios Predict Outcome of COVID-19 Patients? A Multicentric Study

Figures & data

Table 1 Characteristics of the Studied Population

Variant	Group			P-value
	Non-Severe n=185 (37.3%)	Severe n=165 (33.3%)	Critical n=146 (29.4%)
Age/years	33.5 (26–54)	55(47–62)	61(50–69)	<0.001*
Sex/males n (%)	92 (49.5)	94 (57)	87 (60)	0.167**
Smoking n (%)	41 (22%)	36 (21.8%)	29 (20)	0.867**
Co-morbidities
DM n (%) HTN n (%) Cardiovascular diseases n (%) COPD n (%)	16 (8.6)	39 (23.6)	42 (29)	<0.001**
	19 (10.3)	40 (24.2)	73 (50.3)	<0.001**
	10 (5.4)	31 (18.8)	54 (37)	<0.001**
	4 (2.2)	15 (9.1)	20 (13.7)	<0.001***
Laboratory data
CBC median (range)
HB (g/dL)	12 (11–14)	12 (10–13)	12 (11–13)	0.043*
Platelets (×10^9/L)	204 (136–264)	234 (162–325)	231 (167–328)	<0.001*
TLC (×10^9/L)	4 (3.1–6)	8 (5–12)	11 (9–15)	<0.001*
ANC (×10^9/L)	2 (1.4–4)	6 (3–9.5)	9 (7–12)	<0.001*
ALC (×10^9/L)	1.53 (1–2)	1 (1–2)	1 (1–2)	0.049*
AMC (×10^9/L)	0.2 (0–1)	1 (0–1)	1 (0–1)	0.022*
NLR	1.55 (1–3)	4 (2–8)	8 (5–11)	<0.001*
LMR	4 (3–6)	3 (2–5)	2 (1–3)	<0.001*
d-NLR	1 (1–2)	3 (1–5)	5 (3–7)	<0.001*
PLR	131 (91–188)	172 (103–286)	203 (107–324)	0.001*
Inflammatory markers
CRP (mg/l)	20 (4.5–54)	54 (30.1–82)	79 (45–85)	<0.001*
Ferritin (mcg/mL)	189 (68–408)	191(98–450)	145 (40.5–202)	0.001
D- dimer (mcg/mL)	0.81 (0.26–9.2)	3 (0.69–17)	8 (1.5–20)	<0.001
MSCT chest
Bilateral affection or multiple unilateral affection n (%)	172(93)	164(99.4)	146(100)	<0.001***
Oxygen support
Any oxygen aids other than mechanical ventilation n (%)	–	137(83.0)	135(92.5)	<0.001**
Mechanical ventilation n (%)	–	17(10)	105(72.4)	<0.001**
Outcome
Recovery n (%)	172(93)	140(84.8)	51(34.9)	<0.001**
Death n (%)	13(7)	25(15.2)	95(65.1)	<0.001**

Notes: *Kruskal–Wallis test. **Chi square test. ***Fisher's Exact test. Bold is significant p value; P value is significant if <0.05.

Abbreviations: ALC, absolute lymphocyte count; AMC, absolute monocyte count; ANC, absolute neutrophil count; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; DM, diabetes mellitus; d-NLR, derived neutrophil to lymphocyte ratio; HB, hemoglobin; HTN, hypertension; LMR, lymphocyte to monocyte ratio; MSCT, multi-slice computed tomography; n, number; NLR, neutrophil to lymphocyte ratio; PLR, platelets to lymphocyte ratio; TLC, total leukocyte count.

Table 2 ROC Curve Analysis of All Studied Population to Detect Optimal Cut-off Values, Sensitivity and Specificity of the Hematological Ratios

	AUC	P value	95% CI		Cut off Point	Sensitivity	Specificity	+LR	−LR	+PV	−PV	Youden’s Index
			Lower	Upper
NLR	0.838	<0.001	0.803	0.874	>3.5	71.38%	87.03%	5.50	0.33	90.2	64.4	0.5841
d-NLR	0.817	<0.001	0.780	0.854	>2.86	67.20%	89.19%	6.22	0.37	91.3	61.8	0.5639
PLR	0.643	<0.001	0.595	0.692	>192	50.00%	77.62%	2.20	0.65	78.7	48.0	0.2762
LMR	0.285	<0.001	0.239	0.331	≤3	67.64%	65.95%	1.99	0.49	76.8	55.0	0.3395

Notes: The test variable(s): NLR, d-NLR, PLR and LMR has at least one tie between the positive actual state group and the negative actual state group. P value is significant if <0.05.

Abbreviations: AUC, area under curve; CI, confidence interval; d-NLR, derived neutrophil lymphocyte ratio; LMR, lymphocyte monocyte ratio; LR, Likelihood ratio; NLR, neutrophil lymphocyte ratio; PLR, platelet lymphocyte ratio; PV, predictive value; ROC, receiver operating characteristics.

Figure 1 ROC curve was used to study the optimal cut off values of different hematological ratio; NLR (3.5), d-NLR (2.86), and PLR (192). D-NLR specificity (89.19%) NLR (87%) and PL/LR (77.62%). The sensitivity of NLR (71.38%), d-NLR (67.2%) and the PL/LR (50%).

Abbreviations: D-NLR, derived neutrophil lymphocyte ratio; LMR, lymphocyte monocyte ratio; NLR, neutrophil lymphocyte ratio; PLR, platelets lymphocyte ratio.

Figure 2 Survival analysis using Kaplan–Meier curve (A) Kaplan–Meier curves showing survival in non-severe, severe and critical group. (B) Kaplan–Meier curve according to NLR (Neutrophil lymphocyte ratio) of COVID-19 patients. (C) Kaplan–Meier curve according to d-NLR (derived neutrophil lymphocyte ratio) of COVID-19 patients. (D) Kaplan–Meier curve according to PLR (platelets lymphocyte ratio) of COVID-19 patients. Numbers below each cure show number at risk.

Table 3 Identification of Possible Predictors of Severity in COVID-19 Patients

	Univariable Odds Ratio	95% C. I		P value	Multivariable Odds Ratio	95% C.I		P value
		Lower	Upper			Lower	Upper
Age	1.069	1.055	1.084	<0.001	1.056	1.009	1.098	0.018
DM (yes/no)	3.698	2.087	6.551	<0.001	1.852	0.790	4.338	0.156
HTN (yes/no)	4.956	2.923	8.404	<0.001	0.823	0.345	1.963	0.661
Cardiovascular diseases (yes/no)	6.582	3.320	13.048	<0.001	1.796	0.618	5.215	0.282
COPD (yes/ no)	5.759	2.013	16.480	0.001	4.058	0.921	17.878	0.064
NLR	1.602	1.450	1.771	<0.001	1.453	1.123	1.765	0.003
d-NLR	1.913	1.654	2.212	<0.001	1.002	0.827	1.204	0.983
PLR	1.004	1.002	1.006	<0.001	1.000	0.998	1.003	0.681
LMR	0.784	0.726	0.847	<0.001	1.020	0.900	1.156	0.757
CRP	1.013	1.008	1.018	<0.001	1.006	1.003	1.009	0.043
Ferritin	1.001	1.000	1.002	0.154
D- dimer	23.362	12.617	43.259	<0.001	46.957	15.689	140.547	<0.001
Steroid (yes/no)	3.832	1.532	9.583	0.004	1.160	0.315	4.270	0.823
Oxygen aids (yes/no)	40.813	24.061	69.228	<0.001	22.031	11.733	38.621	<0.001
Mechanical (yes/no)	12.452	5.910	26.238	<0.001	1.852	0.736	4.662	0.191

Notes: Bold is significant p value; P value is significant if <0.05.

Abbreviations: COPD, chronic obstructive pulmonary disease; CI, Confidence interval; CRP, C-reactive protein; DM, diabetes mellitus; d-NLR, derived neutrophil to lymphocyte ratio; HTN, hypertension; LMR, lymphocyte to monocyte ratio; NLR, neutrophil to lymphocyte ratio; PLR, platelets to lymphocyte ratio.