Evaluation of lymphocyte count, T-cell subsets and neutrophil-to-lymphocyte ratio as early predictors for severity and outcome of COVID-19 disease-a report from a highly complex hospital in Brazil

Oliveira, Douglas Câmara de; Spiri, Beatriz Sanada; Schluga, Yara Carolina; Justus, Julie Lilian Pimentel; Lopes Neto, Francisco Diego Negrão; Azambuja, Ana Paula de

doi:10.1016/j.htct.2022.05.007

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Hematology, Transfusion and Cell Therapy

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Original article • Hematol., Transfus. Cell Ther. 45 (3) • Jul-Sep 2023 • https://doi.org/10.1016/j.htct.2022.05.007 copy

Evaluation of lymphocyte count, T-cell subsets and neutrophil-to-lymphocyte ratio as early predictors for severity and outcome of COVID-19 disease-a report from a highly complex hospital in Brazil

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction:

Lymphopenia is a laboratory marker of poor prognosis and severity of disease in the SARS-CoV-2 infection. This study aims to describe the immune profile of a Brazilian population.

Methods:

A total of 121 consecutive patients with severe acute respiratory syndrome (SARS) were analyzed between April and June 2020. Routine peripheral blood counts and multiparametric flow cytometry were performed on admission to assess lymphocytes and subsets (CD3, CD4, CD8). Demographic, clinical and laboratory data were collected from hospital sources.

Results:

The total of 116 patients included 63 (54.3%) males; 76 (62.8%) COVID-19 patients were divided, based on clinical characteristics and mechanical ventilation (MV) use, into moderate (n = 41; no MV) and severe (n = 35; MV) groups. The control group (n = 40) was comprised of patients with SARS of different etiologies. All patients had lymphopenia, with overall lymphocyte counts and their subsets considerably lower in severe patients, when compared to the moderate and controls. Patients with a high neutrophil-to-lymphocyte ratio (> 15.2) and T-cell lymphopenia (CD3 < 593 cells/μL, CD4 < 326 cells/μL, CD8 < 121 cells/μL) had a higher risk of being intubated and progressing to death. A total of 39 patients (95.1%) in the moderate group and 54.3% (n = 19) in the severe group were discharged; 28 patients died.

Conclusion:

Laboratory assessment of the neutrophil/lymphocyte ratio and T-cell subsets may be predictive of mortality and may be useful for stratifying COVID-19 patients.

Keywords:
Covid-19; Sars-cov-2; Lymphocytes; T-cell; Flow cytometry

Characteristics	Total (n = 116)	Control (n = 40)	Moderate (n = 41)	Severe (n = 35)	p-value
Age (years)	58 [47.5;68.5]	63 [48;74.5]	53 [46;64]	64 [49;69]	ns
Male (%)	63 (54.3)	16 (40.0)	25 (61.0)	22 (62.9)	0.025
Comorbidities (yes, %)	99 (85.3)	37 (92.5)	28 (68.3)	34 (97.1)	ns
Hospitalization time (days)	10 [5;21]	8 [3.5;13]	6 [4;11]	26 [14;39]	0.064
UCI, yes (%)	65 (56.0)	19 (47.5)	11 (26.8)	35 (100)	ns
MV, yes (%)	44 (37.9)	9 (20.5)	0(0)	35 (100)	ns

Characteristics	Control (I)	Moderate (II)	Severe (III)	p-value (I×II×III)	I×II	I×III	II×III
Globular volume (%)	35.9 [32.2;41.8]	41.6 [37.8;44.2]	38.1 [31.5;42.7]	0.006	0.008	1.000	0.045
Hemoglobin (g/dL)	12.0 [10.2;13.4]	13.9 [12.5;14.4]	12.3 [10.4;13.8]	0.001	0.001	1.000	0.015
Platelets (10³ units/μL)	208.5 [161;316]	269.0 [191;351]	241.0 [181;360]	0.142	-	-	-
Leukocytes (cells/μL)	9565 [6185;13315]	7120 [5700;9140]	11920 [8870;16110]	<0.001	0.126	0.088	<0.001
Neutrophils (cells/μL)	7433 [4281;11711]	5148 [4282;8035]	10635 [7628;14926]	<0.001	0.154	0.021	<0.001
Lymphocytes (cell/μL)	836 [498;1,370]	1052 [594;1,413]	596 [315;977]	0.001	0.526	0.040	<0.001
NLR	7.71 [4.72;15.07]	6.3 [3.82;8.16]	22.29 [9.90;38.60]	<0.001	0.082	0.003	<0.001
CD3+ (cells/μL)	566 [259;962]	740 [409;1,036]	374 [146;633]	<0.001	0.726	0.009	<0.001
CD4+ (cells/μL)	356 [132;613]	389 [244;679]	184 [84;353]	0.001	0.941	0.018	0.001
CD8+ (cells/μL)	172 [93;308]	215 [142;354]	108 [60;219]	0.001	0.587	0.061	0.001
CD19+ (cells/μL)	89 [33;162]	125 [81;194]	115 [65;159]	0.080	-	-	-
CD56+ (cells/μL)	90 [34;154]	160 [101;209]	64 [31;106]	0.001	0.018	0.852	0.001
D-dimer^a a D-dimer was available in 77 patients. (ng/mL FEU)	2.01 [0.82;3.45]	0.58 [0.47;1.65]	2.21 [1.12;3.65]	0.004	0.044	1.000	0.004
C-reactive protein^b b C-reactive protein was available in 102 patients. (mg/L)	5.95 [2.45;12.37]	5.24 [1.58;9.39]	12.66 [8.16;16.00^* * The values surpassing the superior limit of detection available in laboratory. ]	0.005	1.000	0.029	0.005
Ferritin^c c Ferritin was available in 71 patients. (μg/L)	159.82 [106;320]	601 [398;2437]	1052 [427;1675^* * The values surpassing the superior limit of detection available in laboratory. ]	<0.001	<0.001	<0.001	1.000
Troponin^d d Troponin was available in 76 patients. (ng/mL)	10.0 [10.0;26.6]	10.0 [10.0;10,1]	12.2 [10.0;62.8]	0.093	-	-	-

Groups	MV	NoMV	Total	Absolute Risk (%)	p-value
NLR < 15.2	19	65	84	22.6	< 0.001
NLR > 15.2	25	7	32	78.1
Lymph < 489	17	10	27	63.0	0.002
Lymph > 489	27	62	89	30.3
CD3 < 593	32	28	60	53.3	< 0.001
CD3 > 593	12	44	56	21.4
CD4 < 326	28	27	55	50,9	0.006
CD4 > 326	16	45	61	26,2
CD8 < 121	22	19	41	53,7	0.010
CD8 > 121	22	53	75	29,3
Groups	Alive	Death	Total	Absolute Risk (%)	p-value
NLR < 15.2	73	11	84	13.1	< 0.001
NLR > 15.2	15	17	32	53.1
Lymph < 489	12	15	27	55.6	< 0.001
Lymph > 489	76	13	89	14.6
CD3 < 593	36	24	60	40.0	< 0.001
CD3 > 593	52	4	56	7.1
CD4 < 326	32	23	55	41.8	< 0.001
CD4 > 326	56	5	61	8.2
CD8 < 121	22	19	41	46.3	< 0.001
CD8 > 121	66	9	75	12.0

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] *Corresponding author at: Universidade Federal do Paraná, Hospital de Clínicas, Laboratório de Imunofenotipagem, Rua Padre Camargo, 280, Alto da Glória, CEP: 80060-240, Curitiba, Paraná, Brazil. E-mail address: douglas.camara@ufpr.br (D.C.d. Oliveira).