摘要:SummaryThe identification of patients with coronavirus disease 2019 and high risk of severe disease is a challenge in routine care. We performed cell phenotypic, serum, and RNA sequencing gene expression analyses in severe hospitalized patients (n = 61). Relative to healthy donors, results showed abnormalities of 27 cell populations and an elevation of 42 cytokines, neutrophil chemo-attractants, and inflammatory components in patients. Supervised and unsupervised analyses revealed a high abundance ofCD177, a specific neutrophil activation marker, contributing to the clustering of severe patients. Gene abundance correlated with high serum levels of CD177 in severe patients. Higher levels were confirmed in a second cohort and in intensive care unit (ICU) than non-ICU patients (P < 0.001). Longitudinal measurements discriminated 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.Graphical abstractDisplay OmittedHighlights•Increase in B cells, activated CD8 T cells, NKT, and γδ T NKG2A + cells in severe COVID-19•Severe COVID-19 is characterized by an increase of neutrophil and inflammatory markers•Serum CD177 protein levels are increased in patients with COVID-19 in ICU•Sustained high levels of CD177 discriminated recovery and death of patients with COVID-19Immunology; Virology