Virology Research Center, National Research Institute of Tuberculosis and Lung diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Int Arch Allergy Immunol. 2021;182(3):254-262. doi: 10.1159/000514202. Epub 2021 Jan 26.
Although the pathophysiology of coronavirus disease 2019 (COVID-19) is not clearly defined, among the proposed mechanisms, immune system dysfunction is more likely than others. The aim of this study was to clarify the characteristics and clinical significance of dynamic changes of lymphocyte subsets in the course of COVID-19.
In this prospective study, the levels of peripheral lymphocyte subsets including CD4+, CD8+, CD4+CD25+FOXP3+, CD38+, CD3+HLA-DR+, CD19+, CD20+, and CD16+CD56+ cells were measured by flow cytometry in 52 confirmed hospitalized patients with COVID-19 at the day of admission and after 7 days of care. Clinical response was defined as improvement in symptoms (fever, dyspnea, and cough as well as blood oxygen saturation), and patients who met these criteria after 1 week of admission were classified as early responders; others who survived and finally discharged from the hospital were classified as late responders and patients who died were categorized as nonresponders. Immunophenotyping of studied cell changes on the first day of admission and 7 days after treatment were compared. Besides, the correlation between cellular subset variation and clinical response and outcome were analyzed.
Total counts of white blood cell, T cells, CD4+ T cells, CD8+ T cells, CD38+ lymphocytes, and CD3+HLA-DR+ lymphocytes were significantly increased in both early and late responders. No statistically significant difference was observed in CD4+/CD8+ ratio, B cells, FOXP3+Treg lymphocytes, and FOXP3 median fluorescence intensity among studied groups. According to the multivariate analysis, an increase in CD4+ T cells (p = 0.019), CD8+ T cells (p = 0.001), and administration of interferon (p < 0.001) were independent predictors of clinical response.
We found an increasing trend in total T cells, T helpers, cytotoxic T cells, activated lymphocytes, and natural killer cells among responders. This trend was not statistically significant among nonresponders. The findings of this study may enhance our knowledge about the pathogenesis of COVID-19.
尽管 2019 年冠状病毒病(COVID-19)的发病机制尚不清楚,但在提出的机制中,免疫系统功能障碍的可能性大于其他机制。本研究旨在阐明 COVID-19 病程中淋巴细胞亚群动态变化的特征和临床意义。
在这项前瞻性研究中,通过流式细胞术检测了 52 例确诊的 COVID-19 住院患者入院当天和护理 7 天后外周血淋巴细胞亚群(包括 CD4+、CD8+、CD4+CD25+FOXP3+、CD38+、CD3+HLA-DR+、CD19+、CD20+和 CD16+CD56+细胞)的水平。临床反应定义为症状改善(发热、呼吸困难和咳嗽以及血氧饱和度),入院后 1 周符合这些标准的患者被归类为早期反应者;存活并最终出院的患者被归类为晚期反应者,死亡的患者被归类为无反应者。比较入院第 1 天和治疗后第 7 天的免疫表型研究细胞变化,并分析细胞亚群变化与临床反应和结局的相关性。
早期和晚期反应者的白细胞、T 细胞、CD4+T 细胞、CD8+T 细胞、CD38+淋巴细胞和 CD3+HLA-DR+淋巴细胞总数均显著增加。在研究组之间,CD4+/CD8+比值、B 细胞、FOXP3+Treg 淋巴细胞和 FOXP3 中值荧光强度无统计学差异。根据多变量分析,CD4+T 细胞增加(p=0.019)、CD8+T 细胞增加(p=0.001)和干扰素治疗(p<0.001)是临床反应的独立预测因素。
我们发现反应者中总 T 细胞、辅助性 T 细胞、细胞毒性 T 细胞、活化淋巴细胞和自然杀伤细胞呈增加趋势。非反应者中没有统计学意义。本研究的结果可能会增强我们对 COVID-19 发病机制的认识。