COVID-19 SARS-CoV-2 infection exhibits wide inter-individual clinical variability, from silent infection to severe disease and death. The identification of high-risk patients is a continuing challenge in routine care. We aimed to identify factors that influence clinical worsening. We analyzed 52 cell populations, 71 analytes, and RNA-seq gene expression in the blood of severe patients from the French COVID-19 study upon hospitalization (n = 61). COVID-19 patients showed severe abnormalities of 27 cell populations relative to healthy donors (HDs). Forty-two cytokines, neutrophil chemo-attractants, and inflammatory components were elevated in COVID-19 patients. Supervised gene expression analyses showed differential expression of genes for neutrophil activation, interferon signaling, T- and B-cell receptors, EIF2 signaling, and ICOS-ICOSL pathways in COVID-19 patients. Unsupervised analysis confirmed the prominent role of neutrophil activation, with a high abundance of CD177, a specific neutrophil activation marker. CD177 was the most highly differentially-expressed gene contributing to the clustering of severe patients and its abundance correlated with CD177 protein serum levels. CD177 levels were higher in COVID-19 patients from both the French and confirmatory Swiss cohort (n = 203) than in HDs (P< 0.01) and in ICU than non-ICU patients (P< 0.001), correlating with the time to symptoms onset (P = 0.002). Longitudinal measurements showed sustained levels of serum CD177 to discriminate between patients with the worst prognosis, leading to death, and those who recovered (P = 0.01). These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.

中文翻译：

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CD177是中性粒细胞活化的特定标志，是COVID-19严重程度和死亡的标志

从无声感染到严重的疾病和死亡，COVID-19 SARS-CoV-2感染表现出广泛的个体间临床差异。在常规护理中，高风险患者的识别是一个持续的挑战。我们旨在确定影响临床恶化的因素。我们对法国COVID-19住院治疗后重症患者血液中的52个细胞群体，71种分析物和RNA-seq基因表达进行了分析（n = 61）。相对于健康捐献者（HD），COVID-19患者显示27个细胞群体的严重异常。在COVID-19患者中，有42种细胞因子，中性粒细胞趋化因子和炎症成分升高。有监督的基因表达分析显示嗜中性粒细胞激活，干扰素信号传导，T细胞和B细胞受体，EIF2信号传导，和COSID-19患者的ICOS-ICOSL通路。无监督的分析证实了嗜中性粒细胞活化的显着作用，其中CD177（一种特定的嗜中性粒细胞活化标记物）含量很高。CD177是表达最重的基因，可导致重症患者聚集，其丰度与CD177蛋白血清水平相关。来自法国和瑞士确诊人群（n = 203）的COVID-19患者的CD177水平高于HDs（P <0.01）和ICU患者，而非ICU患者（P <0.001），与出现症状的时间相关发作（P = 0.002）。纵向测量显示，血清CD177的持续水平可以区分预后最差，导致死亡的患者和康复的患者（P = 0.01）。