新型冠状病毒肺炎淋巴细胞亚群与严重程度的相关分析

doi:10.19723/j.issn.1671-167X.2020.06.014

摘要/Abstract

摘要：

目的:了解不同临床亚型新型冠状病毒肺炎(corona virus disease 19, COVID-19)患者淋巴细胞亚群的差异。方法:选取2020年2月8日至3月28日在华中科技大学同济医学院附属同济医院中法新城院区由三家援鄂医疗队负责的隔离病房收治的81例COVID-19患者为研究对象。根据相关诊断标准,将患者的疾病状态分为普通型(35例)、重型(39例)、危重型(7例)。检测血常规、淋巴细胞亚群等指标,比较不同临床亚型组患者间各指标是否存在差异。结果:三组患者淋巴细胞、T淋巴细胞、CD4⁺T淋巴细胞、CD8⁺T淋巴细胞、自然杀伤(natural killer,NK)细胞绝对数等指标差异均有统计学意义(P<0.05),危重型患者上述指标均明显低于普通型及重型患者,且随疾病严重程度加重呈递减趋势。22例患者首次检测时T淋巴细胞、B淋巴细胞、CD4⁺T淋巴细胞、CD8⁺T淋巴细胞及NK细胞绝对数、CD4⁺/CD8⁺六项指标均在正常参考值范围内,59例患者上述指标存在异常,以NK细胞和CD8⁺T淋巴细胞绝对数减少最为常见(61%,56%)。将NK、CD8⁺T淋巴细胞绝对数均低于正常参考值范围患者作为一组,其余指标异常患者作为一组,前者危重型患者较多(普通型:重型:危重型分别为4:8:7 vs. 19:21:0,P=0.001),且死亡病例均在此组(6例 vs. 0例,P=0.001)。15例患者B淋巴细胞绝对数低于正常参考值范围,余64例均在正常参考值范围内,减低组与正常组普通型:重型:危重型分别为4:7:4和30:31:3,减低组危重型患者比例多于正常组,两组间差异有统计学意义(P=0.043)。结论:COVID-19患者临床亚型越危重淋巴细胞各亚群绝对数越低。

关键词: 冠状病毒感染, 肺炎, 病毒性, 淋巴细胞亚群

Abstract:

Objective: To understand the differences in lymphocyte subsets in patients with different clinical classifications of corona virus disease 19 (COVID-19). Methods: Eighty-one patients with COVID-19 who were admitted to the isolation ward under the responsibility of three medical aid teams in the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from February 8, 2020 to March 28, 2020, were selected to collect clinical data. According to the relevant diagnostic criteria, the disease status of the patients was classified into moderate cases (n=35), severe cases (n=39) and critical cases (n=7) when lymphocyte subset testing was performed. Their blood routine tests, lymphocyte subsets and other indicators were tested to compare whether there were differences in each indicator between the patients of different clinical classification groups. Results: The differences in the absolute count of total lymphocytes, T-lymphocytes, CD4⁺T-lymphocytes, CD8⁺T-lymphocytes and natural killer (NK) cells among the three groups of patients were all statistically significant (P<0.05), and the critical cases were significantly lower than the moderate and severe cases in the above indicators, and the indicators showed a decreasing trend with the severity of the disease. In 22 patients, the six indicators of the absolute count of T-lymphocytes, B-lymphocytes, CD4⁺T-lymphocytes, CD8⁺T-lymphocytes and NK cells, CD4⁺/CD8⁺ ratio were all within the normal reference range in the first test, and 59 patients had abnormalities of the above indicators, with the absolute count of NK cells and CD8⁺ T lymphocytes decreasing most frequently (61%, 56%). The patients with the absolute count of NK cells and CD8⁺ T lymphocytes below the normal reference range were one group, and the remaining abnormal patients were the other group. There were more critical cases in the former group (moderate:severe:critical cases were 4:8:7 vs. 19:21:0, respectively, P=0.001), and all the deaths were in this group (6 cases vs. 0 case, P=0.001). The absolute B lymphocyte count was below the normal reference range in 15 patients, and the remaining 64 cases were within the normal range. The ratio of moderate, severe and critical cases in the reduced group was 4:7:4, and the ratio of critical cases was more in normal group which was 30:31:3, and the difference between the two groups was statistically significant (P=0.043). Conclusion: The more critical the clinical subtype of patients with COVID-19, the lower the absolute count of each subset of lymphocytes.

Key words: Coronavirus infections, Pneumonia, viral, Lymphocyte subsets

中图分类号:

R563.12

包芳,史尉利,胡静,张娣,高东晗,夏云霞,景红梅,克晓燕,葛庆岗,沈宁. 新型冠状病毒肺炎淋巴细胞亚群与严重程度的相关分析[J]. 北京大学学报（医学版）, 2020, 52(6): 1075-1081.

Fang BAO,Wei-li SHI,Jing HU,Di ZHANG,Dong-han GAO,Yun-xia XIA,Hong-mei JING,Xiao-yan KE,Qing-gang GE,Ning SHEN. Analysis of the correlation between lymphocyte subsets and severity of corona virus disease 19[J]. Journal of Peking University (Health Sciences), 2020, 52(6): 1075-1081.

图/表 8

表1

不同临床亚型患者基本资料"

Characteristic	Moderate (n=35)	Severe (n=39)	Critical (n=7)	P value
Male:Female	18:17	17:22	4:3	0.856
Age/years, M (P₂₅, P₇₅)	58 (44, 63)	68 (58, 73)^*	62 (59, 75)	0.001
Diabetes, n	7	20	4	0.010
Hypertension, n	10	22	2	0.038
Diabetes + Hypertension, n	3	10	0	0.039
Time from onset to test/d, $x -$ ±s	36.3±10.0	31.6±8.3	34.3±19.1	0.136

表1

表2

表3

首次检测淋巴细胞亚群正常组及异常组基本资料"

Characteristic	Normal (n=22)	Abnormal (n=59)	P
Male:Female	12:10	27:32	0.618
Age/years, $x -$ ±s	52.3±13.3	62.7±12.6	0.002
Clinical classifications (Moderate:Severe:Critical)	12:10:0	23:29:7	0.069
Time from onset to test/d, $x -$ ±s	35.1±9.7	33.4±10.7	0.431
Deaths, n	0	6	0.271

表3

表4

首次检测时淋巴细胞亚群计数处于正常范围患者基本资料"

Characteristic	Moderate (n=12)	Severe (n=10)	P
Male:Female	8:4	4:6	0.412
Age/years, $x -$ ±s	49.0±12.1	56.2±14.3	0.107
Time from onset to test/d, $x -$ ±s	37.8±10.8	31.8±7.5	0.228

表4

表5

表6

NK细胞、CD8+ T淋巴细胞低于正常参考值范围组与其他指标异常组患者比较"

Items	NK & CD8⁺ T cell both decrease (n=19)	Other index anomaly (n=40)	P
Males:Females	8:11	19:21	0.698
Age/years, $x -$ ±s	67.1±11.1	60.6±13.0	0.063
Clinical classifications (Moderate:Severe:Critical)	4:8:7	19:21:0	0.001
Time from onset to test/d, $x -$ ±s	32.6±13.5	33.8±9.2	0.526
Deaths, n	6	0	0.001

表6

表7

B淋巴细胞计数减低组与正常组比较"

Items	B-lymphocyte decrease (n=15)	B-lymphocyte normal (n=64)	P
Males:Females	8:7	30:34	0.652
Age/years, $x -$ ±s	63.5±10.9	59.5±13.7	0.381
Clinical classifications (Moderate:Severe:Critical)	4:7:4	30:31:3	0.043

表7

表8

参考文献 14

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Characteristic	Moderate (n=35)	Severe (n=39)	Critical (n=7)	P
Leukocyte/(×10⁹/L)	5.69±1.51	5.75±1.53	12.18±2.76	<0.001
Neutrophil/%	54.56±7.07	60.22±8.38	90.73±4.19	<0.001
Neutrophil/(×10⁹/L)	2.95 (2.35, 3.51)	3.36 (2.91, 3.66)	11.49 (9.67, 12.72)	<0.001
Lymphocyte/%	32.51±6.64	27.04±7.65	4.74±3.09	<0.001
Lymphocyte/(×10⁹/L)	1.82±0.51	1.52±0.50	0.52±0.19	<0.001
Monocyte/%	9.38±2.14	9.35±2.06	3.87±1.32	<0.001
Monocyte/(×10⁹/L)	0.53±0.16	0.54±0.20	0.46±0.17	0.693
Eosinophil/%	2.8 (1.9, 3.9)	2.1 (1.5, 3.2)	0.1 (0.05, 0.75)	<0.001
Eosinophil/(×10⁹/L)	0.17±0.11	0.17±0.17	0.05±0.06	0.010
Basophil/%	0.51±0.25	0.52±0.36	0.21±0.23	0.018
Basophil/(×10⁹/L)	0.03 (0.02, 0.04)	0.03 (0.01, 0.04)	0.01 (0.01, 0.02)	0.173
CD3⁺CD19^-T-cell/%	74.00±7.03	73.72±10.14	64.84±14.87	0.125
CD3⁺CD19^-T-cell/(cells/μL)	1 292±395	1 094±408	295±156	<0.001
CD3^-CD19⁺B-cell/%	12.27±4.96	12.64±7.05	23.77±18.78	0.055
CD3^-CD19⁺B-cell/(cells/μL)	225±126	180±101	110±91	0.033
CD4⁺T-cell/%	47.61±7.89	45.56±7.70	44.66±16.01	0.501
CD4⁺T-cell/(cells/μL)	838±304	675±260	212±145	<0.001
CD8⁺T-cell/%	23.08±6.06	25.73±9.69	18.86±11.80	0.216
CD8⁺T-cell/(cells/μL)	410±135	383±198	77±39	<0.001
CD3^-/CD16⁺CD56⁺NK cell/%	12.99±6.85	12.95±6.24	10.13±8.54	0.584
CD3^-/CD16⁺CD56⁺NK cell/(cells/μL)	212±106	185±101	39±28	<0.001
T⁺B⁺NK cell/%	99.25±0.52	99.33±0.51	98.74±0.95	0.054
T⁺B⁺NK cell/(cells/μL)	1 729±464	1 435±505	444±182	<0.001
CD4⁺/CD8⁺	2.14±0.76	2.08±1.07	3.35±1.97	0.242

Items	Below normal range	In normal range	Above normal range
CD3⁺CD19^-T-cell	27 (46)	32 (54)	0
CD3^-CD19⁺B-cell	15 (25)	42 (71)	2 (3)
CD3^-/CD16⁺CD56⁺NK cell	36 (61)	23 (39)	0
CD4⁺T-cell	24 (41)	34 (58)	1 (2)
CD8⁺T-cell	33 (56)	26 (44)	0
CD4⁺/CD8⁺	1 (2)	41 (69)	17 (29)

Items	B-lymphocyte decrease (n=5)	B-lymphocyte normal (n=33)	P
Time from onset to test/d, M(P₂₅, P₇₅)	45.0 (28.5, 51.0)	39.0 (32.0, 43.0)	0.585
IgM/(AU/mL), M(P₂₅, P₇₅)	59.47 (42.79, 76.05)	39.42 (14.29, 106.21)	0.449
IgG/(AU/mL), M(P₂₅, P₇₅)	209.03 (92.91, 329.47)	173.70 (149.15, 207.09)	0.645