Background

The pathogenesis of coronavirus disease 2019 (COVID-19) is still incompletely understood, but it seems to involve immune activation and immune dysregulation.

Objective

We examined the parameters of activation of different leukocyte subsets in COVID-19–infected patients in relation to disease severity.

Methods

We analyzed plasma levels of myeloperoxidase (a marker of neutrophil activation), soluble (s) CD25 (sCD25) and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) (markers of T-cell activation and exhaustion), and sCD14 and sCD163 (markers of monocyte/macrophage activation) in 39 COVID-19–infected patients at hospital admission and 2 additional times during the first 10 days in relation to their need for intensive care unit (ICU) treatment.

Results

Our major findings were as follows: (1) severe clinical outcome (ICU treatment) was associated with high plasma levels of sTIM-3 and myeloperoxidase, suggesting activated and potentially exhausted T cells and activated neutrophils, respectively; (2) in contrast, sCD14 and sCD163 showed no association with need for ICU treatment; and (3) levels of sCD25, sTIM-3, and myeloperoxidase were inversely correlated with degree of respiratory failure, as assessed by the ratio of Pao₂ to fraction of inspired oxygen, and were positively correlated with the cardiac marker N-terminal pro-B–type natriuretic peptide.

Conclusion

Our findings suggest that neutrophil activation and, in particular, activated T cells may play an important role in the pathogenesis of COVID-19 infection, suggesting that T-cell–targeted treatment options and downregulation of neutrophil activation could be of importance in this disorder.

中文翻译：

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严重COVID-19患者的血浆sTIM-3水平升高

背景

冠状病毒疾病2019（COVID-19）的发病机理仍未完全了解，但似乎涉及免疫激活和免疫失调。

目的

我们检查了感染COVID-19的患者中不同白细胞亚群的激活参数与疾病严重程度的关系。

方法

我们分析了血浆髓过氧化物酶（中性粒细胞活化的标志物），可溶性CD25（sCD25）和可溶性T细胞免疫球蛋白粘蛋白结构域3（sTIM-3）（T细胞活化和衰竭的标志物）和sCD14的水平在入院时感染39例受COVID-19感染的患者中的sCD163和sCD163（单核细胞/巨噬细胞激活的标志物），以及在前10天中因需要加护病房（ICU）治疗而另外2次的情况。

结果

我们的主要发现如下：（1）严重的临床结果（ICU治疗）与sTIM-3和髓过氧化物酶的血浆水平高相关，分别提示活化的T细胞和可能耗尽的T细胞以及活化的中性粒细胞。（2）相反，sCD14和sCD163与ICU治疗的需求无关。（3）sCD25，sTIM-3和髓过氧化物酶的水平与呼吸衰竭的程度呈负相关，如通过Pa o ₂与吸氧分数的比率所评估，并且与心脏标记物N端脯氨酸呈正相关。 -B型利钠肽。

结论

我们的发现表明，嗜中性粒细胞活化，特别是活化的T细胞可能在COVID-19感染的发病机理中起重要作用，这表明针对T细胞的治疗选择和嗜中性粒细胞活化的下调在这种疾病中可能很重要。