Detection of abnormal lymphocytes in the peripheral blood of COVID-19 cancer patients: diagnostic and prognostic possibility

Figures & data

Table 1. Clinical features of the cancer patients with COVID-19.

Parameter		Frequency
Type of cancer	Hematological	39 (46.4%)
	Solid	45 (53.7%)
Disease status	Remission	24 (28.6%)
	Stationary or progressive	60 (71.4%)
Comorbidities	No	73 (86.9%)
	Yes	11 (13.1%)
Blood stream infection	No	74 (88.1%)
	Yes	10 (11.9%)
DCL	No	76 (90.5%)
	Yes	8 (9.5%)
ICU admission	No	58 (69%)
	Yes	26 (31%)
Ventilation	Yes	18 (21.4%)
	No	66 (78.6%)
Death	No	69 (82.1%)
	Yes	15 (17.9%)

ICU: intensive care unit, DCL: disturbed conscious level.

Table 2. Assessment of the clinical and laboratory markers among the three patients’ groups.

Patients’ characteristics		COVID-19, cancer (n = 84)	COVID-19, non-cancer (n = 20)	Control (n = 30)	P-value
Age (years)^#		38 (1–71)^a	42 (26–61)^ab	46 (37–57)^b	0.028
Hb (gm/dL)*		10.2 ± 2.6^a	10.4 ± 1.4^a	14.5 ± 1^b	P < .001
MCV*		92.4 ± 8.3	81.2 ± 6.5	85.8 ± 5	0.738
MHC*		27.6 ± 3.3	26.1 ± 2.7	27.7 ± 1.5	0.084
RDW^#		15.8 (12–27)^a	15.9 (13–24)^a	13.4 (13–16)^b	P < 0.001
Platelets^#		278 (5–724)	242 (38–274)	249 (191–377)	0.480
MPV*		10.2 ± 1.1	10.6 ± 0.6	10.2 ± 1.1	0.421
TLC (×10^9/L)^#		7.8 (0.06–31)^a	7.9 (4.9–26.7)^b	8 (3.6–12.6)^b	0.005
Neutrophils (10^3/µL)^#		4.1 (0–28.6)^a	7.3 (4–25.5)^b	4.2 (1–5.6)^a	0.001
Neutrophil (%)^#		56.7 (4–92)^a	86 (81–96)^b	49.7 (29–60)^a	P < 0.001
Lymphocytes (10^3/µL)^#		1.5 (0.09–6.6)^a	0.65 (0.3–2.5)^a	2.7 (1.9–7.2)^b	P < 0.001
Lymphocyte (%)^#		22.9 (3–93)^a	10.6 (1.7–35)^b	38.7 (26–57)^c	P < .001
Monocytes (10^3/µL)^#		0.58 (0–4.6)^ab	0.36 (0.2–0.8)^a	0.65 (0.3–1.2)^b	0.026
Monocyte%^#		7.9 (0–53.7)^a	5.2 (2.7–6.9)^b	8.6 (6.2–13.8)^a	P < .001
Eosinophils (10^3/µL)^#		0.03 (0–0.56)^a	0.08 (0–0.3)^a	0.13 (0–0.36)^b	P = .001
Basophil (10^3/µL)^#		0 (0–0.06)^a	0 (0–0.08)^a	0.2 (0.05–0.8)^b	P < .001
LDH^#		347 (127–1890)^a	320 (133–767)^a	150 (125–190)^b	P <0 .001
CRP^#		34.7 (0–406)^a	47 (3–207)^a	5 (1–6)^b	P <0 .001
Ferritin^#		3778 (10–6180)^a	606 (10–739)^a	43 (13–168)^b	P < 0.001
ALT^#		22 (6–280)^a	34 (15–74)^b	19 (7–35)^b	0.021
AST^#		22 (9–275)	25 (15-51)	15 (5–34)	0.116
Creatinine^#		0.8 (0–4)	0.8 (0–35)	0.6 (0.5–1.2)	0.186
Urea^#		26 (12-284)	34.5 (12–300)	30 (15–43)	0.071
Gender	Male	49 (58.3%)	9 (45.0%)	18 (60%)	0.210
	Female	35 (41.7%)	11 (55.0%)	12 (40%)
Degree of COVID	Mild	34 (40.5%)	12 (60%)		0.133
	Moderate	24 (28.6%)	6 (30%)
	Severe	36 (31%)	2 (10%)
Giant platelets	No	36 (42.9%)	9 (45.0%)	26 (86.7%)	P < 0.001
	Yes	48 (57.1%)	11 (55.0%)	4 (13.3%)
Blasts	No	74 (88.1%)	20 (100%)	30 (100%)	0.040
	Yes	10 (11.9%)	0 (0.0%)	0 (0.0%)
Shift to left	No	66 (78.6%)	8 (40.0%)	30 (100%)	P < 0.001
	Yes	18 (21.4%)	12 (60.0%)	0 (0.0%)
Hypogranulation	No	76 (90.5%)	20 (100%)	26 (86.7%)	0.258
	Yes	8 (9.5%)	0 (0.0%)	4 (13.3%)
Toxic granulation	No	57 (67.9%)	20 (100%)	28 (93.3%)	0.001
	Yes	27 (32.1%)	0 (0.0%)	2 (6.7%)
Pelger-Heut	No	32 (38.1%)	16 (80.0%)	30 (100%)	P < 0.001
	Yes	52 (61.9%)	4 (20.0%)	0 (0.0%)
vaculated, aggressive, monocytes	No	30 (35.7%)	9 (45.0%)	20 (66.7%)	0.014
	Yes	54 (64.3%)	11 (55.0%)	10 (33.3%)
Mature lymphocytes	No	19 (22.6%)	0 (0.0%)	0 (0.0%)	0.001
	Yes	65 (77.4%)	20 (100%)	30 (100%)
Plasmacytoid lymphocytes	No	22 (26.2%)	13 (65%)	26 (86.7%)	P < 0.001
	Yes	62 (73.8%)	7 (35.0%)	4 (13.3%)
Monocytoid and ballerina	No	38 (45.2%)	20 (100%)	28 (93.3%)	P <0 .001
	Yes	46 (54.8%)	0 (0.0%)	2 (6.7%)
Covicytes	No	33 (39.3%)	9 (45%)	30 (100%)	P <0 .001
	Yes	51 (60.7%)	11 (55%)	0 (0.0%)
Degree of lymphopenia	<0.7	31 (36.9%)	10 (50%)	0 (0.0%)	P < 0.001
	>0.7	53 (63.1%)	10 (50%)	30 (100%)

ALT: alanine transaminase, AST: aspartate transaminase, CRP: C- reactive protein, Hb: Haemoglobin concentration, IG: immature granulocyte, LDH: lactate dehydrogenase, MCH: mean corpuscular hemoglobin, MCV: mean corpuscular volume, MPV: mean platelet volume, RDW: red cell distribution width, TLC: total leukocyte count. The P-value is significant if <.05. Groups having different letters are statistically different. *Data are presented as mean ± SD, ^#data are presented as median (interquartile range).

Figure 1. Morphological characteristics of the peripheral blood cells in COVID-19 cancer patients showing: (A) Giant platelets. (B) Neutrophils with toxic granulations, bright mode. (C) Neutrophils with Pelger-Huet abnormality, bright mode. (D) Large sided aggressive looking monocytes with cytoplasmic vacuolations, 100× magnification.

Figure 2. (A) Assessment of the Covicytes in patients’ groups. (B–E) Atypical lymphocytes with clumpy chromatin and basophilic cytoplasm with large granular tail (Covicytes), 100× magnification.

Figure 3. (A) The plasmacytoid lymphocyte, atypical lymphocyte with dark blue cytoplasm and slightly eccentric nucleus. (B) The monocytoid and ballerina looking lymphocytes were reactive lymphocytes that characteristically scalloping the neighboring cells, 100× magnification. (C) and (D) NK/T-cell lymphoma in leukaemic phase described by Leach M and Bain BJ, cited from the book ‘From the Image to the Diagnosis’, 1st edition. Page 58 [25].

Table 3. Association between the Covicytes and the clinical and laboratory features of the cancer COVID-19 patients.

Patients’ characteristics		Covicytes		P-value
		No (n = 33)	Yes (n = 51)
Age (years)^#		39.5 (8–71)	41 (1–67)	0.299
Hb (gm/dL)*		8.6 ± 2	10.8 ± 2.3	P < 0.001
MCV*		81.5 ± 7	84.5 ± 8.7	0.465
MHC*		27.2 ± 2.8	27.7 ± 3.5	0.058
RDW^#		16 (12–26)	15.6 (12–44)	0.679
Platelets^#		222.5 (31–666)	289 (36–724)	P < 0.001
MPV*		10.4 ± 1.04	10.2 ± 1.2	0.456
TLC (×10^9/L)^#		8.5 (0.49–31)	7.97 (0.95–23.4)	0.287
NRBC^#		0 (0–5)	0 (0–8)	0.861
Neutrophils (10^3/µL)^#		5.7 (0.16–28.6)	4.3 (0.24–20.4)	0.465
Neutrophil (%)^#		67.5 (8–92)	60 (17–92)	0.585
Lymphocytes (10^3/µL) ^#		1.3 (0.3–3.3)	1.7 (0.1–4.4)	0.023
Lymphocyte (%)^#		22.6 (5.2–55)	23.7 (0–53.7)	0.922
Shift to lift^#		0.32 (0–4.3)	0.03 (0.01–2.1)	0.019
Monocytes (10^3/µL)^#		0.69 (0.06–4.6)	0.76 (0.02–1.8)	0.504
Monocyte%^#		10.3 (2.6–53.7)	8 (1.6–31.7)	0.340
Eosinophils (10^3/µL)^#		0.03 (0–0.45)	0.08 (0–0.56)	0.004
Basophil (10^3/µL)^#		0 (0–0.03)	0 (0–0.02)	0.514
LDH^#		298 (127–1890)	204 (129–410)	0.035
CRP^#		58 (0–406)	31.5 (0–300)	0.049
Ferritin^#		2516 (135–4897)	4979 (3778–6180)	1.00
ALT^#		24.5 (6–280)	16.5 (6–235)	0.028
AST^#		25 (9–275)	22 (9–262)	0.498
T. bilirubin^#		0.7 (0–5)	0.4 (0–3)	0.079
Albumin^#		3 (2–192)	2.3 (2–239)	0.226
Creatinine^#		0.8 (0–13)	0.8 (0–4)	0.383
Urea		45.8 (13–284)	25.5 (12–74)	0.046
Sex	male	20 (60.6%)	29 (56.9%)	0.822
	Female	13 (39.4%)	22 (43.1%)
Death	No	28 (84.8%)	41 (80.4%)	0.772
	Yes	5 (15.2%)	10 (19.6%)
ICU admission	No	25 (75.8%)	33 (64.7%)	0.339
	Yes	8 (24.2%)	18 (35.3%)
Disease status	Remission	12 (36.4%)	12 (23.5%)	0.225
	Stationary or progressive	21 (63.6%)	39 (76.5%)
Degree of COVID	Mild and moderate	25 (75.8%)	33 (64.7%)	0.339
	Severe	8 (24.2%)	18 (35.3%)
Ventilation	Yes	6 (18.2%)	10 (19.6%)	0.871
	No	27 (81.8%)	41 (80.4%)
Comorbidities	No	27 (81.8%)	46 (90.2%)	0.328
	Yes	6 (18.2%)	5 (9.8%)
Blood stream infection	No	26 (78.8%)	48 (94.1%)	0.044
	Yes	7 (21.2%)	3 (5.9%)
DCL	No	28 (84.8%)	48 (94.1%)	0.253
	Yes	5 (15.2%)	3 (5.9%)
Liver disease	No	27 (81.8%)	48 (94.1%)	0.145
	Yes	6 (18.2%)	3 (5.9%)
Renal disease	No	29 (87.9%)	47 (92.2%)	0.706
	Yes	4 (12.1%)	4 (7.8%)
Type of cancer	Hematological	18 (54.5%)	21 (41.3%)	0.171
	Solid	15 (45.5%)	30 (66.7%)
Giant platelets	No	21 (63.6%)	15 (29.4%)	0.003
	Yes	12 (36.4%)	36 (70.6%)
Blasts	No	27 (81.8%)	47 (92.2%)	0.181
	Yes	6 (18.2%)	4 (7.8%)
Shift to left	No	25 (75.8%)	41 (80.4%)	0.786
	Yes	8 (24.2%)	10 (19.6%)
Hypogranulation	No	29 (87.9%)	47 (92.2%)	0.706
	Yes	4 (12.1%)	4 (7.8%)
Toxic granulation	No	25 (75.8%)	32 (62.7%)	0.240
	Yes	8 (24.2%)	19 (37.3%)
Pelger-Heut	No	20 (60.6%)	12 (23.5%)	0.001
	Yes	13 (39.4%)	39 (76.5%)
Vacuolated, aggressive, monocytes	No	18 (54.5%)	12 (23.5%)	0.005
	Yes	15 (45.5%)	39 (76.5%)
Mature lymphocytes	No	14 (42.4%)	5 (9.8%)	0.001
	Yes	19 (57.6%)	46 (90.2%)
Plasmacytoid	No	18 (54.5%)	4 (7.8%)	P < 0.001
	Yes	15 (45.5%)	47 (92.2%)
Monocytoid &ballerina	No	23 (69.7%)	15 (29.4%)	P < 0.001
	Yes	10 (30.3%)	36 (70.6%)
Degree of lymphopenia	<0.7	14 (42.4%)	17 (33.3%)	P = 0.489
	>0.7	19 (57.6%)	34 (66.7%)

ALT: alanine transaminase, AST: aspartate transaminase, CRP: C- reactive protein, DCL: disturbed conscious level, Hb: Haemoglobin concentration, ICU: intensive care unit, LDH: lactate dehydrogenase, MCH: mean corpuscular hemoglobin, MCV: mean corpuscular volume, MPV: mean platelet volume, RDW: red cell distribution width, TLC: total leukocyte count. The P-value is significant if <.05. *Data are presented as mean ± SD, ^#data are presented as median (interquartile range).

Table 4. Association between Covicytes and clinical features of the non-cancer COVID-19 patients.

Patients’ characteristics		Covicytes		P-value
		No (n = 9)	Yes (n = 11)
Age (years)^#		42 (38–60)	50 (26–61)	0.824
Hb (gm/dL)*		8.9 ± 0.54	11.6 ± 0.52	P < 0.001
MCV*		83.8 ± 9.2	79.1 ± 1.6	0.169
MHC*		27.5 ± 3.4	24.9 ± 1.1	0.050
RDW^#		19.9 (16–24)	15.3 (13–17)	0.001
Platelets^#		242 (38–263)	263 (142–274)	0.020
MPV*		10.5 ± 0.51	10.7 ± 0.71	0.699
TLC (×10^9/L)^#		6 (4.9–26.7)	7.3 (5.9–11.8)	0.824
Neutrophils (10^3/µL)^#		12 (4–25)	7.3 (4.8–12)	0.689
Neutrophil (%)^#		94 (82–96)	81.8 (81–86)	0.050
Lymphocytes (10^3/µL)^#		0.5 (0.3–0.6)	0.8 (0.7–2)	P < 0.001
Lymphocyte (%)^#		2.5 (1.7–11.4)	13 (8.7–13.8)	0.003
Monocytes (10^3/µL)^#		0.36 (0.2–0.7)	0.4 (0.3–0.8)	0.328
Monocyte%^#		2.8 (2.7–6.9)	5.2 (2.3–5.7)	0.088
PTT^#		35 (30–51)	29 (25–32)	0.001
D-dimer^#		700 (440–1042)	1000 (300–4500)	0.412
LDH^#		320 (294–669)	238 (133–767)	0.201
CRP^#		59 (35–103)	28 (3–207)	0.331
Ferritin^#		693 (600–739)	499 (10–704)	0.010
ALT^#		36 (29–74)	30 (15–44)	0.016
AST^#		30 (24–35)	24 (15–51)	0.201
Creatinine^#		0.8 (0–5)	0.7 (1–35)	0.969
Urea^#		40 (12–162)	30 (22–300)	0.824
Sex	Male	7 (77.8%)	2 (18.2%)	0.022
	Female	2 (22.2%)	9 (81.8%)
Degree of COVID	Mild	8 (88.9%)	4 (36.4%)	0.053
	Moderate	1 (11.1%)	5 (45.5%)
	Severe	0 (0%)	2 (18.2%)
Giant platelets	No	7 (77.8%)	2 (18.2%)	0.022
	Yes	2 (22.2%)	9 (81.8%)
Shift to left	No	2 (22.2%)	6 (54.5%)	0.197
	Yes	7 (77.8%)	5 (45.5%)
Pelger-Heut	No	5 (55.6%)	11 (100.0%)	0.026
	Yes	4 (44.4%)	0 (0.0%)
Plasmacytoid	No	9 (100.0%)	4 (36.4%)	0.005
	Yes	0 (0.0%)	7 (63.6%)
vaculated, aggressive, monocytes	No	7 (77.8%)	2 (18.2%)	0.022
	Yes	2 (22.2%)	9 (81.8%)
Degree of lymphopenia	<0.7	9 (100%)	1 (9.1%)	P = 0.001
	>0.7	0 (0.0%)	10 (90.9%)

ALT: alanine transaminase, AST: aspartate transaminase, CRP: C-reactive protein, Hb: Haemoglobin concentration, LDH: lactate dehydrogenase, MCH: mean corpuscular hemoglobin, MCV: mean corpuscular volume, MPV: mean platelet volume, PT: prothrombin time, RDW: red cell distribution width, TLC: total leukocyte count. The P-value is significant if <.05. *Data are presented as mean ± SD, ^#data are presented as median (interquartile range).

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Data availability statement

All required data and materials are available upon request, except for the personal data of the patients.