糖皮质激素对新型冠状病毒肺炎患者T淋巴细胞亚群的影响

Effects of corticosteroid on T lymphocyte subsets in patients with coronavirus disease 2019

目的观察新型冠状病毒肺炎(简称新冠肺炎)患者外周血T淋巴细胞亚群改变的特点及糖皮质激素对其影响。方法对武汉市第一医院收治的进行了T淋巴细胞亚群检测的376例新冠肺炎患者进行回顾性分析,按照临床分型分为普通型、重型、危重型及死亡病例,对重型患者根据是否运用糖皮质激素治疗进行分组对比分析。结果根据病情严重程度,包括普通型患者118例(31.4%),重型患者215例(57.2%),危重型患者43例(11.4%)。死亡6例(1.6%),均为危重型。(1)重型患者与普通型患者比较,总淋巴细胞[(1 359.2±597.9)×106比(1 703.7±702.4)×106/L,LSD-t=4.786,P<0.001]、总T淋巴细胞[(949.2±454.0)×106比(1 235.5±555.7)×106/L,LSD-t=5.175,P<0.001]、CD8+T细胞[(336.8±189.8)×106比(461.7±242.8)×106/L,LSD-t=5.332,P<0.001]显著减少,CD4+/CD8+比值(1.81±0.92比1.64±0.74,LSD-t=1.574,P=0.116)增加无显著差异;危重型患者与重型患者比较,CD4+/CD8+比值(2.23±1.24比1.81±0.92,LSD-t=2.627,P=0.009)显著增加,CD8+T细胞[(232.5±159.8)×106比(336.8±189.8)×106/L,LSD-t=2.867,P=0.004]显著减少,总淋巴细胞[(1 161.1±583.7)×106比(1 359.2±597.9)×106/L,LSD-t=1.772,P=0.077]、总T淋巴细胞[(790.5±419.3)×106比(949.2±454.0)×106/L,LSD-t=1.846,P=0.066]减少,无显著差异;死亡患者与危重型患者比较均无显著差异。(2)在215例重型患者中,与未使用糖皮质激素患者比较,使用糖皮质激素治疗3~5 d后患者总T淋巴细胞[(770.6±480.3)×106比(986.3±440.7)×106/L,t=2.666,P=0.008]和CD4+/CD8+比值(1.30±0.73比1.91±0.92,t=3.771,P<0.001)均显著性减少。结论新冠肺炎患者T淋巴细胞亚群变化主要表现为T淋巴细胞数量减少和CD4+/CD8+比值增加,且与病情严重程度正相关;糖皮质激素治疗可缓解CD4+/CD8+比值上升,但加剧了T淋巴细胞减少。

Objective To explore the effects of corticosteroid on peripheral blood T lymphocyte subsets in patients with coronavirus disease 2019(COVID-19). Methods This was a retrospective study and 376 patients were included in the study. The patients were classified into three type: moderate type(118 patients), severe type(215 patients),critical type(43 patients). Six critical patients died. T lymphocyte subsets were analyzed and compared among these patients. In severe patients, T lymphocyte subsets were compared between no corticosteroid therapy patients(178 patients) and patients who were treated with corticosteroid for 3 to 5 days(37 patients). Results(1) In contrast with those in moderate patients, in severe patients total lymphocytes [(1 359.2±597.9)×106 vs.(1 703.7±702.4)×106/L,LSD-t=4.786, P<0.001], total T lymphocytes [(949.2±454.0)×106 vs.(1 235.5±555.7)×106/L, LSD-t=5.175, P<0.001] and CD8+ T cells [(336.8±189.8)×106 vs.(461.7±242.8)×106/L, LSD-t=5.332, P<0.001] decreased significantly, and CD4+/CD8+ratio(1.81±0.92 vs. 1.64±0.74, LSD-t=1.574, P=0.116) was increased. In contrast with those in severe patients, in critical patients CD4+/CD8+ ratio(2.23±1.24 vs. 1.81±0.92, LSD-t=2.627, P=0.009) increased and CD8+ T cells[(232.5±159.8)×106/L vs.(336.8±189.8)×106/L, LSD-t=2.867, P=0.004] decreased significantly, total lymphocytes [(1 161.1±583.7)×106/L vs.(1 359.2±597.9)×106/L, LSD-t=1.772, P=0.077], total T lymphocytes [(790.5±419.3)×106/L vs.(949.2±454.0)×106/L, LSD-t=1.846, P=0.066] also decreased but without significant difference. There was no significant difference between dead and survived critical patients.(2) In severe type, in contrast with no corticosteroid therapy patients, 37 patients were therapy with corticosteroid for 3 to 5 days, and their total T lymphocytes [(770.6±480.3)×106 vs.(986.3±440.7)×106/L, t=2.666, P=0.008] and CD4+/CD8+ ratio(1.30±0.73 vs. 1.91±0.92, t=3.771, P<0.001) were decreased significantly. Conclusions In COVID-19 patients, lymphocytes, T lymphocytes and CD8+ T cells are decreased, but CD4+/CD8+ ratio is increased, and these changes are positively related to the severity of the disease. After corticosteroid therapy, the increase of CD4+/CD8+ ratio is relieved, but T lymphocytes are decreased further.