The Prognostic Role of Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio in the Risk of Major Adverse Cardiovascular Events and Mortality in Patients with COVID-19: a State-of-the-Art Review

Arbănași, Eliza Mihaela; Russu, Eliza

doi:10.2478/jce-2024-0010

Figures & Tables

A, ROC analysis and AUC for NLR regarding mortality. Values are expressed per 1 s.d. increase regarding the median value. B, Distribution of the optimal cut-off values for NLR regarding mortality. Values are expressed per 1 s.d. increase regarding the median value. C, The position of the optimal cut-off value depending on the sensitivity and specificity of each value, regarding mortality.

A, ROC analysis and AUC for MLR regarding mortality. Values are expressed per 1 s.d. increase regarding the median value. B, Distribution of the optimal cut-off values for MLR regarding mortality. Values are expressed per 1 s.d. increase regarding the median value. C, The position of the optimal cut-off value depending on the sensitivity and specificity of each value, regarding mortality.

The association between NLR and clinical outcomes: ORs, HRs, and survival analyses

Study	Biomarker	OR/HR	95% CI		p value	Outcome	Kaplan–Meier survival analysis	log rank p value

			Lower	Upper
Fois et al.³⁴	NLR	1.02	0.99	1.06	0.10	Mortality	In-hospital mortality based on cut-off value	<0.001
Abrishami et al.²⁰	NLR	1.124	1.01	1.25	0.036	Mortality	–	–
Pakos et al.²¹	NLR	1.038	1.003	1.074	0.031	Mortality	–	–
Allahverdiyev et al.²²	NLR	1.261	1.054	1.509	0.011	Mortality	–	–
Zeng et al.²³	NLR	5.4	2.6	11.1	<0.001	Mortality	Disease deterioration based on cut-off value	<0.001
		21.2	2.8	161.3
		19.8	2.6	151.4
Moradi et al.³⁶	NLR	1.03	1.003	1.07	0.03	Mortality	One-month mortality based on cut-off value	0.16
Rose et al.²⁴	NLR	1.82	1.14	2.95	0.013	Mortality	–	–
Halmaciu et al.²⁵	NLR	24.13	12.2	47.73	<0.001	Mortality	–	–
Arbănași et al.²⁶	NLR	16.32	9.09	29.3	<0.001	Mortality	–	–
Mureșan et al.²⁷	NLR	13.07	8.29	20.62	<0.001	Mortality	–	–
Citu et al.²⁸	NLR	3.85	1.35	10.95	0.01	Mortality	In-hospital mortality based on cut-off value	<0.001
Ghobadi et al.²⁹	NLR	3.57	2.859	4.458	<0.0001	Mortality	In-hospital mortality based on cut-off value for non-elderly and elderly	<0.001 / <0.001
Regolo et al.³⁰	NLR	1.62	–	–	<0.0001	Mortality	In-hospital mortality based on tertiles	<0.0001
Seyfi et al.³¹	NLR	1.121	1.072	1.179	<0.0001	Mortality	–	–
Zhan et al.³²	NLR	2.24	1.49	4.47	<0.001	MACE	6-month MACE based on cut-off value	0.010
Arbănași et al.²⁶	NLR	30.28	13.97	65.6	<0.001	Acute limb ischemia	–	–
Mureșan et al.²⁷	NLR	11.7	7.99	17.13	<0.001	Deep vein thrombosis	–	–
Mureșan et al.²⁷	NLR	10.5	5.86	18.8	<0.001	Acute pulmonary embolism	–	–
Predenciuc et al.³³	NLR	2.46	1.0	6.03	0.04	Major amputation or mortality	–	–

NLR studies and predictive values for clinical outcomes

Study	Year	Country	Biomarker	Study group value	Control group value	Cut-off value	AUC ROC analysis	Sensitivity (%)	Specificity (%)	Outcome
Fois et al.³⁴	2020	Italy	NLR	9.17	5	15.2	0.697	38%	97%	Mortality
Abrishami et al.²⁰	2020	Iran	NLR	5.02	3.02	3.65	0.678	62.5%	60%	Mortality
Pakos et al.²¹	2020	USA	NLR	6.4	4.5	–	–	–	–	Mortality
Allahverdiyev et al.²²	2020	Turkey	NLR	12.1	3.2	3	0.842	92%	53%	Mortality
Zeng et al.²³	2021	China	NLR	5.33	2.14	2.6937	0.828	92.9%	63.9%	Mortality
Moradi et al.³⁶	2021	Iran	NLR	5	4.1	3.3	–	–	–	Mortality
Yildiz et al.³⁷	2021	Belgium	NLR	–	–	5.94	0.665	62%	64%	Mortality
Karaaslan et al.³⁸	2022	Turkey	NLR	9.27	2.73	4.21	0.810	77.1%	73.7%	Mortality
Kudlinski et al.³⁹	2022	Poland	NLR	17.7	12.29	11.57	0.629	63%	60.5%	Mortality
Rose et al.²⁴	2022	Switzerland	NLR	8.2	5.0	–	–	–	–	Mortality
Halmaciu et al.²⁵	2022	Romania	NLR	11.04	3.73	6.97	0.869	80.5%	85.4%	Mortality
Arbănași et al.²⁶	2022	Romania	NLR	8.45	3.01	4.57	0.845	86.6%	72%	Mortality
Mureșan et al.²⁷	2022	Romania	NLR	9.74	5.38	9.4	0.868	81.8%	74.4%	Mortality
Citu et al.²⁸	2022	Romania	NLR	13.83	8.31	9.1	0.689	70%	67%	Mortality
Ghobadi et al.²⁹	2022	Iran	NLR	6.07	4.7	9.38	0.817	73.3%	86.5%	Mortality
Regolo et al.³⁰	2022	Italy	NLR	–	–	11.38	0.772	72.9%	71.9%	Mortality
Seyfi et al.³¹	2023	Iran	NLR	11.3	5.8	7.02	0.760	63%	83%	Mortality
MACE
Strazzulla et al.³⁵	2021	France	NLR	7.5	3.2	–	–	–	–	Acute pulmonary embolism
Zhan et al.³²	2021	China	NLR	16.28	4.75	10.14	0.803	81.2	82.6	MACE
Arbănași et al.²⁶	2022	Romania	NLR	–	–	8.34	0.882	81.6%	87.4%	Acute limb ischemia
Mureșan et al.²⁷	2022	Romania	NLR	–	–	9.63	0.836	77%	77.8%	Deep vein thrombosis
Mureșan et al.²⁷	2022	Romania	NLR	–	–	13.67	0.801	67.7%	81%	Acute pulmonary embolism
Predenciuc et al.³³	2022	Republic of Moldova	NLR	11.1	6.3	5.4	–	–	–	Major amputation or mortality
Khorvash et al.⁴⁰	2022	Iran	NLR	13.9	8.03	–	–	–	–	Acute ischemic stroke

The association between MLR and clinical outcomes: ORs, HRs, and survival analyses

Study	Biomarker	OR/HR	95% CI		p value	Outcome	Kaplan–Meier survival analysis	log rank p value

			Lower	Upper
Fois et al.³⁴	MLR	1.60	0.62	4.09	0.32	Mortality	In-hospital mortality based on cut-off value	0.006
Halmaciu et al.²⁵	MLR	6.49	2.51	22.24	<0.001	Mortality	–	–
Arbănași et al.²⁶	MLR	5.51	3.50	8.67	<0.001	Mortality	–	–
Mureșan et al.²⁷	MLR	6.89	4.64	10.23	<0.001	Mortality	–	–
Citu et al.²⁸	MLR	3.05	1.16	8.05	0.02	Mortality	In-hospital mortality based on cut-off value	<0.001
Ghobadi et al.²⁹	MLR	1.502	1.212	1.86	<0.0001	Mortality	In-hospital mortality based on cut-off value for non-elderly and elderly	<0.001
Arbănași et al.²⁶	MLR	6.82	3.51	13.28	<0.001	Acute limb ischemia	–	–
Mureșan et al.²⁷	MLR	11.19	7.68	16.29	<0.001	Deep vein thrombosis	–	–
Mureșan et al.²⁷	MLR	8.96	5.11	15.69	<0.001	Acute pulmonary embolism	–	–

General characteristics of the studies included in the analysis

Study	Patients, n	Mean age, years	Male sex, n (%)	Hypertension, n (%)	Ischemic heart disease, n (%)	Diabetes, n (%)	Obesity, n (%)	Active smoking, n (%)	Observation
Fois et al.³⁴	119	72	77 (64.7%)	–	–	25 (21%)	27 (22.69%)	36 (30.25%)	NLR, MLR, and PLR
Abrishami et al.²⁰	100	55.5	68 (68%)	33 (33%)	21 (21%)	21 (21%)	25 (25%)	–	NLR and PLR
Pakos et al.²¹	242	66.03	208 (85.95%)	180 (74%)	–	118 (49%)	–	–	NLR
Allahverdiyev et al.²²	455	56	217 (47.7%)	170 (37.4%)	88 (19.3%)	128 (28.1%)	–	–	NLR
Zeng et al.²³	352	>60 years 133 (37.78%)	190 (53.97%)	–	–	–	–	57 (16.19%)	NLR
Zeng et al.²³	352	<60 years 219 (62.22%)	190 (53.97%)	–	–	–	–	57 (16.19%)	NLR
Moradi et al.³⁶	219	–	137 (62.6%)	85 (38.8%)	46 (21%)	83 (38%)	–	23 (10.5%)	NLR
Yildiz et al.³⁷	198	Derivation group 64.4	110 (55%)	101 (51%)	107 (54%)	49 (25%)	–	8 (4%)	NLR
Yildiz et al.³⁷	198	Validation group 65	65 (64%)	52 (51.5%)	45 (44.6%)	22 (21.8%)	–	2 (2%)	NLR
Karaaslan et al.³⁸	191	54.32	94 (49.2%)	72 (37.7%)	–	44 (23%)	–	–	NLR and PLR
Kudlinski et al.³⁹	285	62	189 (66.3%)	153 (55.2%)	26 (9.4%)	57 (20.7%)	134 (47.7%)	20 (7%)	NLR
Rose et al.²⁴	454	–	291 (64.1%)	225 (49.6%)	137 (30.2%)	119 (26.2%)	103 (22.7%)	–	NLR and PLR
Halmaciu et al.²⁵	267	71.19	159 (59.55%)	167 (62.55%)	145 (54.31%)	116 (43.45%)	69 (25.84%)	99 (37.08%)	NLR and MLR
Arbănași et al.²⁶	510	69.6	247 (62.37%)	228 (57.78%)	138 (34.85%)	150 (37.88%)	114 (28.79%)	134 (33.84%)	NLR, MLR, and PLR
Mureșan et al.²⁷	889	70.5	474 (53.32%)	735 (82.67%)	513 (57.70%)	268 (30.14%)	146 (16.42%)	256 (28.79%)	NLR, MLR, and PLR
Citu et al.²⁸	108	63.31	56 (51.9%)	76 (70.4%)	51 (47.2%)	50 (46.3%)	–	–	NLR, MLR, and PLR
Ghobadi et al.²⁹	1,792	Elderly 76.29	988 (55.13%)	–	–	522 (29.12%)	–	–	NLR, MLR, and PLR
Ghobadi et al.²⁹	1,792	Non-elderly 48.35	988 (55.13%)	–	–	522 (29.12%)	–	–	NLR, MLR, and PLR
Regolo et al.³⁰	411	72	237 (57.7%)	244 (59.4%)	70 (17.1%)	111 (27%)	–	–	NLR
Seyfi et al.³¹	312	–	–	–	–	–	–	–	NLR
Strazzulla et al.³⁵	184	–	103 (55.97%)	–	–	–	–	–	NLR and PLR
Zhan et al.³²	159	–	73 (45.91%)	72 (45.28%)	15 (9.43%)	33 (20.75%)	–	53 (33.33%)	NLR
Predenciuc et al.³³	130	71	86 (66.2%)	117 (90%)	106 (81.5)	39 (30%)	–	–	NLR
Khorvash et al.⁴⁰	211	66.28	110 (52.13%)	126 (59.7%)	53 (25.1%)	103 (48.8%)	–	–	NLR

MLR studies and predictive values for clinical outcomes

Study	Year	Country	Patients, n	Biomarker	Study group value	Control group value	Cut-off value	AUC ROC analysis	Sensitivity (%)	Specificity (%)	Outcome
Fois et al.³⁴	2020	Italy	119	MLR	0.429	0.333	0.364	0.617	69%	57%	Mortality
Halmaciu et al.²⁵	2022	Romania	267	MLR	0.75	0.33	0.54	0.826	74.4%	81.6%	Mortality
Arbănași et al.²⁶	2022	Romania	510	MLR	0.62	0.32	0.45	0.758	68.4%	74%	Mortality
Mureșan et al.²⁷	2022	Romania	889	MLR	1.14	0.47	0.78	0.794	71.3%	74%	Mortality
Citu et al.²⁸	2022	Romania	108	MLR	0.83	0.53	0.69	0.661	58%	74%	Mortality
Ghobadi et al.²⁹	2022	Iran	1,792	MLR	0.20	0.16	0.26	0.628	59.4%	62.4%	Mortality
MACE
Arbănași et al.²⁶	2022	Romania	510	MLR	–	–	0.49	0.787	71.4%	71.6%	Acute limb ischemia
Mureșan et al.²⁷	2022	Romania	889	MLR	–	–	0.78	0.824	77%	76.2%	Deep vein thrombosis
Mureșan et al.²⁷	2022	Romania	889	MLR	–	–	0.81	0.766	71%	72.1%	Acute pulmonary embolism

PLR studies and predictive values for clinical outcomes

Study	Year	Country	Patients, n	Biomarker	Study group value	Control group value	Cut-off value	AUC ROC analysis	Sensitivity (%)	Specificity (%)	Outcome
Fois et al.³⁴	2020	Italy	119	PLR	265	214	240	0.572	59%	58%	Mortality
Abrishami et al.²⁰	2020	Iran	100	PLR	202	160.8	–	0.559	–	–	Mortality
Karaaslan et al.³⁸	2022	Turkey	191	PLR	287.5	139.94	189.5	–	–	–	Mortality
Rose et al.²⁴	2022	Switzerland	454	PLR	268.3	215.5	–	–	–	–	Mortality
Arbănași et al.²⁶	2022	Romania	510	PLR	229.83	128.22	177.51	0.775	68.4%	77.5%	Mortality
Mureșan et al.²⁷	2022	Romania	889	PLR	363.16	156.22	266.9	0.819	72%	81.1%	Mortality
Citu et al.²⁸	2022	Romania	108	PLR	345	324	–	–	–	–	Mortality
Ghobadi et al.²⁹	2022	Iran	1,792	PLR	168	154	230	0.585	52.6%	63.1%	Mortality
MACE
Strazzulla et al.³⁵	2021	France	184	PLR	259	204	–	–	–	–	Acute pulmonary embolism
Arbănași et al.²⁶	2022	Romania	510	PLR	–	–	178.99	0.858	81.6%	73.1%	Acute limb ischemia
Mureșan et al.²⁷	2022	Romania	889	PLR	–	–	230.67	0.802	72.8%	76.8%	Deep vein thrombosis
Mureșan et al.²⁷	2022	Romania	889	PLR	–	–	207.06	0.734	74.2%	61.3%	Acute pulmonary embolism

The association between PLR and clinical outcomes: ORs, HRs, and survival analyses

Study	Biomarker	OR/HR	95% CI		p value	Outcome	Kaplan–Meier survival analysis	log rank p value

			Lower	Upper
Fois et al.³⁴	PLR	1.0006	1.00	1.0013	0.058	Mortality	In-hospital mortality based on cut-off value	0.13
Rose et al.²⁴	PLR	1.37	0.79	2.46	0.27	Mortality	–	–
Arbănași et al.²⁶	PLR	7.47	4.71	11.83	<0.001	Mortality
Mureșan et al.²⁷	PLR	11.04	7.34	16.62	<0.001	Mortality
Ghobadi et al.²⁹	PLR	1.451	1.17	1.799	<0.0001	Mortality	In-hospital mortality based on cut-off value for non-elderly and elderly	<0.001 / 0.10
Arbănași et al.²⁶	PLR	12.07	7.71	21.77	<0.001	Acute limb ischemia	–	–
Mureșan et al.²⁷	PLR	8.36	5.82	12.02	<0.001	Deep vein thrombosis	–	–
Mureșan et al.²⁷	PLR	6.26	3.54	11.07	<0.001	Acute pulmonary embolism	–	–

The Prognostic Role of Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio in the Risk of Major Adverse Cardiovascular Events and Mortality in Patients with COVID-19: a State-of-the-Art Review

Figures & Tables

FIGURE 1.

FIGURE 2.

The association between NLR and clinical outcomes: ORs, HRs, and survival analyses

NLR studies and predictive values for clinical outcomes

The association between MLR and clinical outcomes: ORs, HRs, and survival analyses

General characteristics of the studies included in the analysis

MLR studies and predictive values for clinical outcomes

PLR studies and predictive values for clinical outcomes

The association between PLR and clinical outcomes: ORs, HRs, and survival analyses

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