CD177, a specific marker of neutrophil activation, is a hallmark of COVID-19 severity and death

Abstract

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 cohort 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.

ScRNA-Seq study of neutrophils reveals vast heterogeneity and breadth of inflammatory responses in severe COVID-19 patients

“…2B). Remarkably, expression of these genes is attenuated in PMNs from the severe patients, whose neutrophils displayed increased activation markers including GBP5 (activator of NLRP3 inflammasome assembly) (27) and CD177, previously associated with COVID-19 severity and death (28), as well as stress-related genes such as IRAK3, FKBP5, IL1R2 (Fig. 2B).…”

Neutrophil subsets in noncancer liver diseases: Cellular crosstalk and therapeutic targets

“…Destabilizing the CD177:mPR3 complex decreases ANCA-induced neutrophil activation and autoimmune diseases [42]. Another study indicated that CD177 serves as a specific neutrophil activation marker to predict the severity and mortality of COVID-19 [43].…”

Exploring the potential common denominator pathogenesis of system lupus erythematosus with COVID-19 based on comprehensive bioinformatics analysis

“…We used and normalized the data by implementing the R 3.6.1 software package "Limma", and to explore the expression of differential genes (DEGs) in GSE171110 and GSE22098 between disease groups and the healthy controls samples, respectively (14,15). Genes with adjusted P-value less than 0.05 and |log2-fold change (log2FC)| more than 1.0 were defined as statistically DEGs.…”