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

Autor: Giuseppe Pantaleo, Delphine Bachelet, Mathieu Surenaud, Boris P. Hejblum, Fabiola Blengio, Rodolphe Thiébaut, Minerva Cervantes, Matthieu Perreau, Christine Lacabaratz, Yves Levy, Aurélie Wiedemann, Pascaline Tisserand, Mélany Durand, Cédric Laouénan, Yazdan Yazdanpanah, Lila Bouadma, Benjamin Hivert, Jean-François Timsit, Marie Dechenaud, Hakim Hocini, Cécile Lefebvre, Marine Gautier, Emile Foucat
Rok vydání: 2020
Předmět:
DOI: 10.1101/2020.12.12.20246934
Popis: 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.
Databáze: OpenAIRE