Immunocytometric analysis of COVID patients: A contribution to personalized therapy?

Immunocytometric analysis of COVID patients: A contribution to personalized therapy?
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DOI:
10.1016/j.lfs.2020.118355
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发表时间:
2020-11-15
期刊:
影响因子:
6.1
通讯作者:
Parrella, Roberto
Parrella, Roberto
中科院分区:
医学2区
文献类型:
--
作者:
Cacciapuoti, Sara;De Rosa, Annunziata;Parrella, Roberto

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目的:本研究旨在阐明COVID-19的免疫细胞计数改变,COVID-19是一种具有异质性临床表达和不完全确定的病理生理学的潜在致命病毒感染。我们研究了35名新冠肺炎患者在入院时通过细胞荧光测定法检测了一大组淋巴细胞亚群和血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6,IL-17 A和IL-17 A可溶性受体(IL-17 RA)。关键发现:在入院时,50-80%的患者中总淋巴细胞和大多数T和B亚群减少,与疾病严重程度密切相关。而活化的辅助性T细胞1(TH 1)和TH 17细胞则正常或升高。所有患者血清IL-6均升高,而TNF-α和IL-17 A在晚期更高。具有低严重性的患者亚组具有非常高的IL-17 RA水平。Tocilizumab治疗导致3/6例患者的IL-17 A增加,3例患者减少,而3例患者的淋巴细胞数量增加,其他患者没有变化。因此,存在有助于损害呼吸道炎症的相关细胞因子产生。一部分病例中TH 17和IL-17的增加以及低严重程度患者中IL-17 RA(阻止IL-17与细胞受体的相互作用)显著增加的证据表明,一些患者可能受益于靶向IL-17通路的单克隆抗体治疗。免疫细胞荧光标记物可能有助于COVID患者的个性化治疗。
Aims: This study aims to cast light on immunocytometric alterations in COVID-19, a potentially fatal viral infection with heterogeneous clinical expression and a not completely defined pathophysiology.Methods: We studied 35 COVID patients at hospital admission testing by cytofluorimetry a large panel of lymphocyte subpopulations and serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-17A and the soluble receptor of IL-17A (IL-17RA).Key findings: At hospital admission, total lymphocytes and most T and B subpopulations were reduced in 50-80% of patients, with close relationship to disease severity. While activated T helper 1 (TH1) and TH17 cells resulted normal or higher. Serum IL-6 was increased in all patients, while TNF-alpha and IL-17A were higher in advanced stages. A patient subset with low severity had very high IL-17RA levels. Tocilizumab treatment caused an increase of IL-17A in 3/6 patients and a reduction in 3 others, while the lymphocyte number increased in 3 patients and did not change in the others.Significance: Cytofluorimetry revealed a functional exhaustion of most lymphocyte populations in COVID patients not involving activated TH1 and TH17. Consequently, there was a relevant cytokines production that contributes to impair the respiratory inflammation. The increase of TH17 and IL-17 in a subset of cases and the evidence of a significant increase of IL-17RA (that prevents the interaction of IL-17 with the cell receptor) in patients with low severity suggest that some patients could benefit from monoclonal antibodies treatment targeting IL-17 pathway. Immunocytofluorimetric markers may contribute to a personalized therapy in COVID patients.