Y. Lévy, A. Wiedemann, B. Hejblum, M. Durand, C. Lefebvre, M. Surenaud, C. Lacabaratz, M. Perreau, E. Foucat, M. Déchenaud, P. Tisserand, F. Blengio, B. Hivert, M. Gautier, M. Cervantes, D. Bachelet, C. Laouénan, L. Bouadma, J. Timsit, Y. Yazdanpanah, G. Pantaleo, H. Hocini, R. Thiébaut, F. C. Study Group
medRxiv, 2020
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.
Cited by 1 publication.
Field of study: Medicine