新型冠状病毒变异毒株感染的临床特征与预警因素分析

Analysis of clinical characteristics and warning factors in SARS-CoV-2 variants infection

目的探讨不同新型冠状病毒毒株变异感染者的临床特征,为临床尽早发现毒株变异提供预警信号。方法采用病例对照研究,收集2021年01月02日—2021年06月30日105例新型冠状病毒感染者的鼻拭子样本进行病毒基因测序,根据毒株分型分为Delta变异组与非Delta变异组,收集两组研究对象的临床相关数据,比较住院天数、年龄分布、淋巴细胞、中性粒细胞、B淋巴细胞、NK细胞、IL-4、IL-10等指标;根据研究对象病毒阴转天数进行亚组分析,比较免疫学特征的差异,包括淋巴细胞、中性粒细胞、B淋巴细胞、NK细胞、IL-4、IL-10等。结果Delta和非Delta变异组理论住院天数、总淋巴细胞计数、IL-4、IL-10分别为(22.2±8.33)d和(17.60±10.50)d、(1.22±0.86)×10^(9)/L和(1.91±0.70)×10^(9)/L、(0.80±0.30)g/mL和(1.59±0.59)ng/mL、(7.16±7.77)ng/mL和(4.26±3.91)ng/mL,显示Delta变异组住院天数显著延长、总淋巴细胞计数和IL-4降低、IL-10显著增高,差异有统计学意义(t=2.396,4.329,9.072,1.980,P均<0.05),亚组分析显示延迟出院患者中,变异组总淋巴细胞计数和IL-4分别为(1.04±0.60)×10^(9)/L和(0.74±0.25)ng/mL,均较非Delta变异组(1.62±0.56)×10^(9)/L和(1.56±0.52)ng/mL显著降低(P均<0.05)。结论新冠病毒Delta变异株对多种临床特征产生影响,确诊感染者入院12 h内B细胞计数、IL-10浓度增高,IL-2与IL-4浓度下降,提示可能感染新的变异毒株,而发现其总淋巴细胞计数下降,以T细胞减少为主时,强烈提示该类型患者病毒清除受阻,住院时间将延长。

Objective To investigate the influence of the variation of SARS-CoV-2 on the clinical feature,and to provide early warning signs for the variation of SARS-CoV-2 in clinical work.Methods From Jan 2,2021 to Jun 30,2021,a total of105 COVID-19 patients were included in the study using a case-control method.Nasal swab samples were collected from the study subjects,the viral genes were sequenced,and patients were divided into Delta variant group and non-Delta variant group according to their gene sequences.Clinically relevant data were collected from the two groups,and indicators such as days of hospitalization,age distribution,lymphocytes,neutrophils,B lymphocytes,NK cells,IL-4,and IL-10 were compared;subgroup analysis was performed based on the number of days of viral negativity in the study subjects as the basis for grouping,and differences in immunological characteristics were compared,including lymphocytes,neutrophils,B lymphocytes,NK cells,IL-4,IL-10,etc.Results The theoretical hospitalization days of Delta variant group were(22.2±8.33)d,which were significantly longer than(17.6±10.50)d of non-Delta variant group(t=2.396,P<0.05).The total lymphocyte count and IL-4 of Delta variant group were(1.22±0.86)×10^(9)/L and(0.80±0.23)ng/mL,which were significantly lower than corresponding(1.91±0.70)×10^(9)/L and(1.59±0.59)ng/mL of non-Delta variant group(t=4.329,9.072,P<0.05),while IL-10 was(7.16±7.77)ng/mL,which was significantly higher than(4.26±3.91)ng/mL of non-Delta mutation group(t=1.980,P<0.05).Subgroup analysis showed that the total lymphocyte count and IL-4 concentration in Delta variant group were(1.04±0.60)×10^(9)/L and(0.74±0.25)ng/ml,which were significantly lower than corresponding(1.62±0.56)×10^(9)/L and(1.56±0.52)ng/mL in non-Delta variant group,in patients with delayed discharge(P<0.05).Conclutions SARS-CoV-2 variant has an impact on clinical manifestations.The patient’s B cell count and IL-10 concentration increased or IL-2 and IL-4 concentration decreased within12 hours of admission indicated variant virus infection.The decrease of total lymphocyte count,especially T lymphocyte reduction,strongly suggests discharge delay due to viral clearance disorder.