A summary of the diagnostic and prognostic value of hemocytometry markers in COVID-19 patients

Figures & data

Table 1. Changes in white blood cell (WBC) parameters for eleven cohort studies in COVID-19 patients.

Study	Cohort size	Study period	Patient groups	Parameter results					Statistical analysis	Relevant findings
				WBC (× 10^9/L)	All patients	Non-severe	Severe	p value*
Guan et al.	1099	11 December 2019–31 January 2020	Non-severe (926) and Severe (173)	Overall	4.7 (3.5–6.0)	4.9 (3.8 to 6.0)	3.7 (3.0–6.2)		Continuous variables were expressed as medians and interquartile ranges.	Upon admission, leukopenia was present in 33.7% of patients. More patients with severe disease had leukopenia than those with non-severe disease.
				>10.0	58/978 (5.9%)	39/811 (4.8%)	19/167 (11.4%)
				<4.0	330/978 (33.7%)	228/811 (28.1%)	102/167 (61.1%)
Qin et al.	452	10 January 2020–12 February 2020	Non-severe (166) and Severe (286)		5.3 (3.9–7.5)	4.9 (3.7–6.1)	5.6 (4.3–8.4)	<0.001	Continuous variables were described as medians and interquartile ranges (IQRs). Independent group t tests were used for the comparison of means for continuous variables that were normally distributed; conversely, the Mann-Whitney U test was used for continuous variables not normally distributed.	Severe cases had higher WBC counts compared to the non-severe cases (p < 0.001).
Huang et al.	344	25 January 2020–24 March 2020	Non-severe (299) and Severe (45)		4.8 ± 2.1	4.6 ± 1.9	5.7 ± 3.1	0.027	Continuous variables were expressed as means ± SD. The Student t-test was used for the comparison of normally distributed variables and the Mann-Whitney U-test for non-normally distributed variables.	Higher levels of WBC were found in the severe group compared to non-severe (p = 0.027).
Hu et al.	323	8 January 2020–20 February 2020	Non-severe (151) and Severe (171)†	>10.0	23/323(7.1%)	5/140(3.6%)	18/165 (10.9%)	0.009	For continuous variables, student t-test or Mann-Whitney test was used.	The most critical cases in the severe group had even higher percentages of leukocytosis.
Zhang et al.	221	2 January 2020–10 February 2020	Non-severe (166) and Severe (55)	Overall	4.4(3.2–6.6)	4.1(3.1–5.8)	6.2(4.1–9.4)	<0.001	All the continuous variables were determined the normality of the distribution by Kolmogorov-Smirnov test, the normally distributed variables were described as the means ± standard deviation (SD) and the skewed distributed variables were expressed as the median and interquartile range (IQR). Normally distributed continuous variables were compared using the Student t-test and skewed distributed variables by using the Mann- Whitney U test.	Upon admission, WBC counts of 73 (33.0%) of the 221 patients showed leukopenia (white blood cell count < 3.5 × 10^9/L). The severe group had increased WBC counts overall and much more frequently than in the non-severe group (p < 0.001).
				<3.5	73(33.0)	62(37.3)	11(20.0)	0.018
				3.5–9.5	125(56.6)	94(56.6)	31(56.4)	0.973
				>9.5	23(10.4)	10(6.0)	13(23.6)	<0.001
Gong et al.	189	20 January 2020-2 March 2020	Non-severe (161) and Severe (28)			4.6 (3.7, 5.6)	5.2 (4.4, 6.7)	0.03	Continuous variables were expressed as mean (standard deviation [SD]), or median (interquartile range [IQR]), as appropriate. Parametric test (t-test) and non-parametric test (Mann-Whitney U) were used for continuous variables with or without normal distribution, respectively.	WBC count in the survivors was higher than the non-survivors (p = 0.03).
					All patients	Non-survivors	Survivors	p Value
K. Wang et al.	296	7 January 2020–11 February 2020	Non-survivors (19) and Survivors (277)			7.8 (4.7–11.9)	4.7 (3.4–6.4)	<0.001	Continuous variables presented as medians (interquartile ranges). Differences among groups were analyzed using one-way ANOVA and Kruskal-Wallis tests for normally and skewed distributed continuous variables, respectively.	WBC counts were considerably higher in the non-survivor group compared to the survivor group (p < 0.001).
Y. Wang et al.	344	25 January 2020–25 February 2020	Non-survivors (133) and Survivors (211)		6.2 (4.5–8.9)	9.1 (6.1–13.3)	5.3 (4.0–6.9)	<0.001	Continuous variables were expressed as medians and interquartile ranges and Mann-Whitney test was used to test for significance.	WBC counts of non-survivors were increased compared to survivors.
Zhou et al.	191	29 December 2019–31 January 2020	Non-survivors (54) and Survivors (137)	Overall	6.2 (4.5–9.5)	9.8 (6.9–13.9)	5.2 (4.3–7.7)	<0.0001	Continuous and categorical variables were presented as median (IQR) and n (%), respectively. We used the Mann-Whitney U test, χ² test, or Fisher’s exact test to compare differences between survivors and non-survivors where appropriate.	Leukocytosis was associated with death, with non-survivors having increased WBC counts overall (p < 0.0001). Survivors more frequently had leukopenia compared to non-survivors (p < 0.0001).
				<4	32 (17%)	5 (9%)	27 (20%)	<0.0001^‡
				4–10	119 (62%)	24 (44%)	95 (69%)	N/A
				>10	40 (21%)	25 (46%)	15 (11%)	N/A
					All patients	Non-ICU	ICU
Chen et al.	249	20 January 2020–6 February 2020	Non-ICU (227) and ICU (22)	WBC (×10^9/L)	4.71(3.80–5.86)				Continuous variables were described with mean, median, and interquartile range (IQR) values.	On admission, leukopenia was observed in 28.9% of the patients.
Cheng et al.	701	28 January 2020–11 February 2020	All positive COVID-19 patients		7.5 ± 7.5				Continuous variables were expressed as the mean ± standard deviation.	On average, patients had a WBC count within normal range upon admission.

*Two-sided P values of less than .05 were considered statistically significant. ^†Severe and critical patient groups were combined for the purposes of this table. ^‡χ² test comparing all subcategories.

Table 2. Changes in neutrophil parameters for seven cohort studies in COVID-19 patients.

Study	Cohort Size	Study period	Patient groups	Parameter Results					Statistical analysis	Relevant finding
				Neutrophils and NLR	All patients	Non-severe	Severe	p Value*
Qin et al.	452	10 January 2020–12 February 2020	Non-severe (166) and Severe (286)	Neutrophil count (×10^9/L)	3.9 (2.6–5.8)	3.2 (2.1–4.4)	4.3 (2.9–7.0)	<0.001	Continuous variables were described as medians and interquartile ranges (IQRs). Independent group t tests were used for the comparison of means for continuous variables that were normally distributed; conversely, the Mann-Whitney U test was used for continuous variables not normally distributed.	Severe cases had higher neutrophil (4.3 vs 3.2 × 10^9/L; p < 0.001) counts and higher neutrophil-to-lymphocyte ratio (NLR; 5.5 vs 3.2; p < 0.001).
				Neutrophil percentage, %	74.3 (64.3–83.9)	67.5 (57.8–75.8)	77.6 (68.9–86.5)	<0.001
				NLR	4.2 (2.5–7.7)	3.2 (1.8–4.9)	5.5 (3.3–10.0)	<0.001
Huang et al.	344	25 January 2020–24 March 2020	Non-severe (299) and Severe (45)	Neutrophil count (×10^9/L)	3.2 ± 2	3 ± 1.7	4.7 ± 3.3	< 0.001	Continuous variables were expressed as means ± SD. The Student t-test was used for the comparison of normally distributed variables and the Mann-Whitney U-test for non-normally distributed variables.	Higher levels of neutrophils and NLR were found in the severe group (p < 0.001 and 0.002)
				NLR	3.5 ± 4.5	2.9 ± 2.3	7.9 ± 10.1	0.002
Hu et al.	323	8 January 2020–20 February 2020	Non-severe (151) and Severe (171)	Neutrophil count, > 75 (×10^9/L)	100/323(31%)	39/140(27.9%)	61/165 (37%)	0	For continuous variables, student t-test or Mann-Whitney test was used.	The most critical cases in the severe group had neutrophilia much more frequently.
Zhang et al.	221	2 January 2020–10 February 2020	Non-severe (166) and Severe (55)	Neutrophil count (×10^9/L)	3.0(1.9–5.1)	2.6(1.8–4.0)	5.4(2.8–8.4)	<0.001	The normally distributed variables were described as the means ± standard deviation (SD) and the skewed distributed variables were expressed as the median and interquartile range (IQR). Normally distributed continuous variables were compared using the Student t-test and skewed distributed variables by using the Mann- Whitney U test.	Neutrophils were significantly increased in severe patients (p < 0.001).
Gong et al.	189	20 January 2020–2 March 2020	Non-severe (161) and Severe (28)	Neutrophil count (×10^9/L)		2.8 (2.0, 3.6)	3.7 (2.8, 5.2)	<0.01	Continuous variables were expressed as mean (standard deviation [SD]), or median (interquartile range [IQR]), as appropriate. Parametric test (t-test) and non-parametric test (Mann-Whitney U) were used for continuous variables with or without normal distribution, respectively.	Neutrophil count was higher in severe patients compared to non-severe (p <0.01).
					All patients	Non-survivors	Survivors	p Value
K. Wang et al.	296	7 January 2020–11 February 2020	Non-survivors (19) and Survivors (277)	Neutrophil count (×10^9/L)		6.4 (3.2–10.0)	3.0 (2.0–4.4)	<0.001	Continuous variables presented as medians (interquartile ranges). Differences among groups were analyzed using one-way ANOVA and Kruskal-Wallis tests for normally and skewed distributed continuous variables, respectively.	Neutrophils were considerably higher in the non-survivor group than in the survivor group (p < 0.001).
Y. Wang et al.	344	25 January 2020–25 February 2020	Non-survivors (133) and Survivors (211)	Neutrophil count (×10^9/L)	4.7 (2.9–7.6)	8.0 (5.5–12.2)	3.7 (2.5–5.3)	<0.001	Continuous variables were expressed as medians and interquartile ranges and Mann-Whitney test was used to test for significance.	Non-survivors had a higher neutrophil count compared to survivors.

*Two-sided p values of less than 0.05 were considered statistically significant. ^†Severe and critical patient groups were combined for the purposes of this table. NLR: neutrophil-to-lymphocyte ratio.

Table 3. Changes in lymphocyte parameters for eleven cohort studies in COVID-19 patients.

Study	Cohort size	Study period	Patient groups	Parameter Results					Statistical analysis	Relevant findings
				Lymphocytes	All patients	Non-severe	Severe	p value*
Guan et al.	1099	December 11, 2019–31 January 2020	Non-severe (926) and Severe (173)	Lymphocyte count (×10^9/L)	1.0 (0.7–1.3)	1.0 (0.8–1.4)	0.8 (0.6–1.0)		Continuous variables were expressed as medians and interquartile ranges.	On admission, lymphocytopenia was present in 83.2% of the patients. Patients with severe disease had more prominent lymphocytopenia than those with non-severe disease.
				<1.5	731/879 (83.2%)	584/726 (80.4%)	147/153 (96.1%)
Qin et al.	452	10 January 2020–12 February 2020	Non-severe (166) and Severe (286)	Lymphocyte count (×10^9/L)	0.9 (0.6–1.2)	1.0 (0.7–1.3)	0.8 (0.6–1.1)	<.001	Continuous variables were described as medians and interquartile ranges (IQRs). Independent group t tests were used for the comparison of means for continuous variables that were normally distributed; conversely, the Mann-Whitney U test was used for continuous variables not normally distributed.	Severe cases had lower lymphocyte counts. Among 452 patients who underwent laboratory examinations on admission, most of them tended to have lymphopenia and severe cases had lower lymphocytes counts (0.8 vs 1.0 × 10^9/L; p < 0.001).
				Lymphocyte percentage, %	17.5 (10.7–25.1)	21.4 (15.3–32.5)	14.1 (8.8–21.4)	<.001
Huang et al.	344	25 January 2020–24 March 2020	Non-severe (299) and Severe (45)	Lymphocyte count (×10^9/L)	1.2 ± 0.5	1.2 ± 0.5	0.9 ± 0.4	< 0.001	Continuous variables were expressed as means ± SD. The Student t-test was used for the comparison of normally distributed variables and the Mann-Whitney U-test for non-normally distributed variables.	Lower lymphocytes numbers were seen in the severe group compared to non-severe (p < 0.001).
Hu et al.	323	8 January 2020–20 February 2020	Non-severe (151) and Severe (171)†	Lymphocyte count, <20 (×10^9/L)	181/323 (56%)	72/140 (51.4%)	109/165 (66%)	0	For continuous variables, student t-test or Mann-Whitney test was used.	Lymphopenia occurred among 83.6% of patients with unfavorable outcomes. The most critical cases in the severe group had lymphopenia much more frequently. (91.7%) compared to the less severe (61.7%).
Zhang et al.	221	2 January 2020–10 February 2020	Non-severe (166) and Severe (55)	Lymphocyte count (×10^9/L)	0.8 (0.6–1.1)	0.9 (0.6–1.2)	0.7 (0.4–0.9)	<0.001	All the continuous variables were determined the normality of the distribution by Kolmogorov-Smirnov test, the normally distributed variables were described as the means ± standard deviation (SD) and the skewed distributed variables were expressed as the median and interquartile range (IQR). Normally distributed continuous variables were compared using the Student t-test and skewed distributed variables by using the Mann- Whitney U test.	On admission, 163 (73.8%) showed lymphopenia (lymphocyte count <1.1 × 10^9/L). Additionally, the lymphocyte count was significantly decreased in severe patients compared to the non- severe patients (p < 0.001).
				<0.5	39 (17.6)	21 (12.7)	18 (32.7)	0.001
				0.5–1.1	124 (56.2)	94 (56.6)	30 (54.5)	0.788
				>1.1	58 (26.2)	51 (30.7)	7 (12.7)	0.009
Gong et al.	189	20 January 2020–2 March 2020	Non-severe (161) and Severe (28)	Lymphocyte count (×10^9/L)		1.3 (1.0, 1.8)	1.0 (0.8, 1.4)	<0.01	Continuous variables were expressed as mean (standard deviation [SD]), or median (interquartile range [IQR]), as appropriate. Parametric test (t-test) and non-parametric test (Mann-Whitney U) were used for continuous variables with or without normal distribution, respectively.	Lymphocyte count was higher in severe patients compared to non-severe (p <0.01).
					All patients	Non-survivors	Survivors	p Value
K. Wang et al.	296	7 January 2020–11 February 2020	Non-survivors (19) and Survivors (277)	Lymphocyte count (×10^9/L)		0.7 (0.5–1.0)	1.0 (0.7–1.4)	0.003	Continuous variables presented as medians (interquartile ranges). Differences among groups were analyzed using one-way ANOVA and Kruskal-Wallis tests for normally and skewed distributed continuous variables, respectively.	Lymphocyte counts were lower in the non-survivor group than in the survivor group (p = 0.003).
Y. Wang et al.	344	25 January 2020–25 February 2020	Non-survivors (133) and Survivors (211)	Lymphocyte count (×10^9/L)	0.9 (0.6–1.2)	0.6 (0.4–0.7)	1.0 (0.8–1.4)	<0.001	Continuous variables were expressed as medians and interquartile ranges and Mann-Whitney test was used to test for significance.	Lymphocytopenia occurred in almost 70% of patients and was predominantly found in non-survivors.
Zhou et al.	191	29 December 2019–31 January 2020	Non-survivors (54) and Survivors (137)	Lymphocyte count (×10^9/L)	1.0 (0.6–1.3)	0.6 (0.5–0.8)	1.1 (0.8–1.5)	<0.0001	Continuous and categorical variables were presented as median (IQR) and n (%), respectively. We used the Mann-Whitney U test , χ² test, or Fisher’s exact test to compare differences between survivors and non-survivors where appropriate.	Lymphopenia was associated with death and baseline lymphocyte count was significantly higher in survivors than non-survivors; in survivors, lymphocyte count was lowest on day 7 after illness onset and improved during hospitalization, whereas severe lymphopenia was observed until death in non-survivors (p <0.0001).
				<0.8	77 (40%)	41 (76%)	36 (26%)	<0.0001
					All patients	Non-ICU	ICU
Chen et al.	249	20 January 2020–6 February 2020	Non-ICU (227) and ICU (22)	Lymphocyte count (×10^9/L)	1.12 (0.79–1.49)				Continuous variables were described with mean, median, and interquartile range (IQR) values.	On admission, lymphopenia was observed in 47.4% of the patients.
Cheng et al.	701	28 January 2020–11 February 2020	All positive COVID-19 patients	Lymphocyte count (×10^9/L)	0.9 ± 0.5				Continuous variables were expressed as the mean ± standard deviation.	On average, patients had lymphopenia upon admission.

*Two-sided p values of less than 0.05 were considered statistically significant. ^†Severe and critical patient groups were combined for the purposes of this table.

Table 4. Changes in platelet parameters for seven cohort studies in COVID-19 patients.

Study	Cohort size	Study period	Patient groups	Parameter results					Statistical analysis	Relevant findings
				Platetets and PLR	All patients	Non-severe	Severe	p value*
Guan et al.	1099	11 December 2019–31 January 2020	Non-severe (926) and Severe (173)	Platelet count (×10^9/L)	168(132–207)	172 (139–212)	137.5 (99–179.5)		Continuous variables were expressed as medians and interquartile ranges.	On admission, thrombocytopenia was present in 36.2% of patients and was more prevalent in severe patients.
				<150	315/869 (36.2%)	225/713 (31.6%)	90/156 (57.7%)
Hu et al.	323	8 January 2020–20 February 2020	Non-severe (151) and Severe (171)^†	Platelet count, <100 (×10^9/L)	16/323(5%)	4/138(2.9%)	12/165 (7.2%)	0.095	For continuous variables, student T-test or Mann-Whitney test was used.	The most critical cases in the severe group more frequently had thrombocytopenia.
Zhang et al.	221	2 January 2020–10 February 2020	Non-severe (166) and Severe (55)	Platelet count (×10^9/L)	175 (127–209)	175 (136–213)	169 (111–202)	0.050	All the continuous variables were determined the normality of the distribution by Kolmogorov-Smirnov test, the normally distributed variables were described as the means ± standard deviation (SD) and the skewed distributed variables were expressed as the median and interquartile range (IQR). Normally distributed continuous variables were compared using the Student t-test and skewed distributed variables by using the Mann- Whitney U test.	Platelet count in the severe group was only slightly lower than the other groups (p = 0.05).
Gong et al.	189	20 January 2020–2 March 2020	Non-severe (161) and Severe (28)	Platelet count (×10^9/L)		180.0 (147.0, 221.0)	167.0 (139.5, 200.0)	0.09	Continuous variables were expressed as mean (standard deviation [SD]), or median (interquartile range [IQR]), as appropriate. Parametric test (t-test) and non-parametric test (Mann-Whitney U) were used for continuous variables with or without normal distribution, respectively.	PLR was increased in severe patients compared to non-severe (p = 0.05).
				PLR		131.0 (96.6, 177.4)	174.8 (117.7, 210.0)	0.05
					All patients	Non-survivors	Survivors	p Value
Zhou et al.	191	29 December 2019–31 January 2020	Non-survivors (54) and Survivors (137)	Platelet count (×10^9/L)	206.0 (155.0–262.0)	165.5 (107.0–229.0)	220.0 (168.0–271.0)	<0.0001	Continuous and categorical variables were presented as median (IQR) and n (%), respectively. We used the Mann-Whitney U test, χ² test, or Fisher’s exact test to compare differences between survivors and non-survivors where appropriate.	Survivors had a higher a platelet count than the non-survivors (p <0.0001).
Y. Wang et al.	344	25 January 2020–25 February 2020	Non-survivors (133) and Survivors (211)	Platelet count (×10^9/L)	189 (142–257)	159 (112–218)	211 (161–290)	<0.001	Continuous variables were expressed as medians and interquartile ranges and Mann-Whitney test was used to test for significance.	Survivors had a higher platelet count compared to non-survivors.
					All patients
Cheng et al.	701	28 January 2020–11 February 2020	All positive COVID-19 patients	Platelet count (×10^9/L)	213 ± 94				Continuous variables were expressed as the mean ± standard deviation.	On average, patients had a platelet count within normal range upon admission.

*Two-sided p values of less than 0.05 were considered statistically significant. ^†Severe and critical patient groups were combined for the purposes of this table. PLR: platelet-to-lymphocyte ratio.