癌症合并新型冠状病毒肺炎患者的FLARE评分与循环中性粒细胞

The FLARE Score and Circulating Neutrophils in Patients with Cancer and COVID-19 Disease.

作者信息

Seguí Elia, Torres Juan Manuel, Auclin Edouard, Casadevall David, Peiro Carmona Sara, Aguilar-Company Juan, García de Herreros Marta, Gorría Teresa, Laguna Juan Carlos, Rodríguez Marta, González Azucena, Epaillard Nicolas, Gavira Javier, Bolaño Victor, Tapia Jose C, Tagliamento Marco, Teixidó Cristina, Arasanz Hugo, Pilotto Sara, Lopez-Castro Rafael, Mielgo-Rubio Xabier, Urbano Cristina, Recondo Gonzalo, Diaz Pavon Mar, Bluthgen Maria Virginia, Minatta José Nicolas, Lupinacci Lorena, Brasó-Maristany Fara, Prat Aleix, Vlagea Alexandru, Mezquita Laura

机构信息

Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.

Department of Medical Oncology, Hospital Clinic of Barcelona, 08036 Barcelona, Spain.

出版信息

Cancers (Basel). 2024 Aug 26;16(17):2974. doi: 10.3390/cancers16172974.

DOI:10.3390/cancers16172974

PMID:39272832

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11393969/

Abstract

PURPOSE

Inflammation and neutrophils play a central role in both COVID-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on COVID-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations.

METHODS

We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during COVID-19 infection. Additionally, a single-center prospective cohort study provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and the severity of COVID-19 disease.

RESULTS

Prior to COVID-19, 25% of patients with cancer exhibited elevated dNLR, which increased to 55% at the time of COVID-19 diagnosis. We developed the FLARE score, incorporating both tumor- and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group ( < 0.0001). This score proved to be an independent predictor of early mortality. This prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe COVID-19 infection.

CONCLUSIONS

A pre-existing tumor-induced pro-inflammatory state significantly impacts COVID-19 outcomes in patients with cancer. The FLARE score, derived from circulating inflammatory markers, emerges as an easy-to-use, globally accessible, effective tool for clinicians to identify patients with cancer at heightened risk of severe COVID-19 complications and early mortality who might benefit most from immediate and intensive treatment strategies. Furthermore, our findings underscore the significance of immature neutrophils in the progression of COVID-19 in patients with cancer, advocating for further investigation into how these cells contribute to both cancer and COVID-19 disease.

摘要

目的

炎症和中性粒细胞在新冠病毒疾病（COVID-19）和癌症中均起着核心作用。我们旨在评估癌症患者中预先存在的肿瘤相关炎症对COVID-19预后的影响，并阐明循环中性粒细胞亚群的作用。

方法

我们对524例癌症合并严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染患者进行了多中心回顾性分析，评估临床结局与COVID-19感染前及感染期间收集的循环炎症生物标志物之间的关系。此外，一项单中心前瞻性队列研究提供了探索性分析数据，评估循环中性粒细胞的免疫表型和炎症细胞因子。主要终点为30天死亡率和COVID-19疾病的严重程度。

结果

在COVID-19之前，25%的癌症患者表现出dNLR升高，在COVID-19诊断时这一比例增加到55%。我们制定了FLARE评分，纳入肿瘤和感染诱导的炎症，将患者分为四个预后组。预后不良组的30天死亡率为68%，显著高于预后良好组的23%（P<0.0001）。该评分被证明是早期死亡率的独立预测因素。这项前瞻性分析显示，癌症合并严重COVID-19感染患者的中性粒细胞向未成熟形式转变，且白细胞介素-6水平更高。

结论

预先存在的肿瘤诱导的促炎状态显著影响癌症患者的COVID-19预后。基于循环炎症标志物得出的FLARE评分，成为临床医生易于使用、全球通用且有效的工具，可用于识别癌症患者中发生严重COVID-19并发症和早期死亡风险较高的患者，这些患者可能从即刻强化治疗策略中获益最大。此外，我们的研究结果强调了未成熟中性粒细胞在癌症患者COVID-19进展中的重要性，提倡进一步研究这些细胞如何在癌症和COVID-19疾病中发挥作用。