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 (p< 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.
目的：炎症与中性粒细胞在COVID-19疾病和癌症中均发挥核心作用。本研究旨在评估癌症患者中既存的肿瘤相关炎症对COVID-19临床结局的影响，并阐明循环中性粒细胞亚群的作用机制。方法：我们对524例合并SARS-CoV-2感染的癌症患者开展多中心回顾性分析，评估COVID-19感染前后采集的循环炎症生物标志物与临床结局的关联性。同时，通过单中心前瞻性队列研究数据进行探索性分析，评估循环中性粒细胞的免疫表型及炎症细胞因子水平。主要终点为30天死亡率和COVID-19疾病严重程度。结果：在感染COVID-19前，25%的癌症患者表现出dNLR升高，该比例在COVID-19确诊时增至55%。我们开发了整合肿瘤性与感染性炎症指标的FLARE评分系统，将患者分为四个预后组。不良预后组的30天死亡率达68%，显著优于预后良好组的23%（p<0.0001）。该评分被证实是早期死亡率的独立预测因子。前瞻性分析显示，合并重症COVID-19感染的癌症患者存在中性粒细胞向幼稚表型转化及IL-6水平升高的现象。结论：既存的肿瘤诱导促炎状态显著影响癌症患者的COVID-19临床结局。基于循环炎症标志物构建的FLARE评分，可作为临床医生识别COVID-19重症并发症和早期死亡高风险癌症患者的便捷、普适、有效的工具，这类患者可能从及时强化的治疗策略中获益最大。此外，我们的研究结果强调了幼稚中性粒细胞在癌症患者COVID-19病程进展中的重要作用，建议进一步探究这些细胞在癌症与COVID-19疾病中的共同作用机制。
The FLARE Score and Circulating Neutrophils in Patients with Cancer and COVID-19 Disease
肿瘤(癌症)患者之家