CD177, a specific marker of neutrophil activation, is associated with coronavirus disease 2019 severity and death

Yves Lévy; Aurélie Wiedemann; Boris P Hejblum; Mélany Durand; Cécile Lefebvre; Mathieu Surénaud; Christine Lacabaratz; Matthieu Perreau; Emile Foucat; Marie Déchenaud; Pascaline Tisserand; Fabiola Blengio; Benjamin Hivert; Marine Gauthier; Minerva Cervantes-Gonzalez; Delphine Bachelet; Cédric Laouénan; Lila Bouadma; Jean-François Timsit; Yazdan Yazdanpanah; Giuseppe Pantaleo; Hakim Hocini; Rodolphe Thiébaut; French COVID cohort study group

doi:10.1016/j.isci.2021.102711

CD177, a specific marker of neutrophil activation, is associated with coronavirus disease 2019 severity and death

iScience. 2021 Jul 23;24(7):102711. doi: 10.1016/j.isci.2021.102711. Epub 2021 Jun 10.

Authors

Yves Lévy^{1

2}, Aurélie Wiedemann¹, Boris P Hejblum^{1

3}, Mélany Durand^{1

3}, Cécile Lefebvre¹, Mathieu Surénaud¹, Christine Lacabaratz¹, Matthieu Perreau⁴, Emile Foucat¹, Marie Déchenaud¹, Pascaline Tisserand¹, Fabiola Blengio¹, Benjamin Hivert³, Marine Gauthier³, Minerva Cervantes-Gonzalez^{5

6

7}, Delphine Bachelet^{5

7}, Cédric Laouénan^{5

7}, Lila Bouadma⁸, Jean-François Timsit⁸, Yazdan Yazdanpanah^{6

7}, Giuseppe Pantaleo^{1

4

9}, Hakim Hocini¹, Rodolphe Thiébaut^{1

3

10}; French COVID cohort study group

Affiliations

¹ Vaccine Research Institute, Université Paris-Est Créteil, Faculté de Médecine, INSERM U955, Team 16, Hopital Henri Mondor, 51 Av Marechal de Lattre de Tassigny, 94010 Créteil, France.
² Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, Service Immunologie Clinique, Créteil, France.
³ Univ. Bordeaux, Department of Public Health, INSERM U1219 Bordeaux Population Health Research Centre, Inria SISTM, UMR 1219, 146 Rue Leo Saignat, 33076 Bordeaux, France.
⁴ Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
⁵ AP-HP, Hôpital Bichat, Département Épidémiologie Biostatistiques et Recherche Clinique, INSERM, Centre d'Investigation clinique-Epidémiologie Clinique 1425, F-75018 Paris, France.
⁶ AP-HP, Hôpital Bichat, Service de Maladies Infectieuses et Tropicales, F-75018 Paris, France.
⁷ Université de Paris, INSERM, IAME UMR 1137, F-75018 Paris, France.
⁸ APHP- Hôpital Bichat - Médecine Intensive et Réanimation des Maladies Infectieuses, Paris, France.
⁹ Immunology and Allergy Service, Department of Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
¹⁰ CHU de Bordeaux, Pôle de Santé Publique, Service d'Information Médicale, Bordeaux, France.

Abstract

The 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 of CD177, 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.

Keywords: immunology; virology.