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LOX-1-Expressing Immature Neutrophils Identify Critically-Ill COVID-19 Patients at Risk of Thrombotic Complications.
Combadière, Behazine; Adam, Lucille; Guillou, Noëlline; Quentric, Paul; Rosenbaum, Pierre; Dorgham, Karim; Bonduelle, Olivia; Parizot, Christophe; Sauce, Delphine; Mayaux, Julien; Luyt, Charles-Edouard; Boissonnas, Alexandre; Amoura, Zahir; Pourcher, Valérie; Miyara, Makoto; Gorochov, Guy; Guihot, Amélie; Combadière, Christophe.
  • Combadière B; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Adam L; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Guillou N; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Quentric P; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Rosenbaum P; Assistance Publique - Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
  • Dorgham K; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Bonduelle O; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Parizot C; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Sauce D; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Mayaux J; Assistance Publique - Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
  • Luyt CE; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Boissonnas A; Assistance Publique - Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Service de Pneumologie, Médecine Intensive et Réanimation, Paris, France.
  • Amoura Z; Service de Médecine Intensive Réanimation, Institut de Cardiologie, Assistance Publique - Hôpitaux de Paris (AP-HP), Sorbonne Université, Hôpital Pitié - Salpêtrière, Paris, France.
  • Pourcher V; Sorbonne Université, Inserm, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
  • Miyara M; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
  • Gorochov G; Service de Médecine Interne 2, Institut E3M, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, France.
  • Guihot A; Assistance Publique - Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Service de Maladies infectieuses et Tropicales, Paris, France.
  • Combadière C; Sorbonne Université, Institut national de santé et de recherche medicale (Inserm), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
Front Immunol ; 12: 752612, 2021.
Article in English | MEDLINE | ID: covidwho-1456293
ABSTRACT

Background:

Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity.

Objective:

We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients' clinical characteristics.

Methods:

We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients.

Results:

The Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10-CD64+ immature neutrophils (ImNs). Cellular profiling revealed three distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the interleukin-3 receptor alpha (CD123), or programmed death-ligand 1 (PD-L1) overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1- or CD123-expressing ImNs is positively correlated with clinical severity, cytokine storm (IL-1ß, IL-6, IL-8, TNFα), acute respiratory distress syndrome (ARDS), and thrombosis. BALs of patients with ARDS were highly enriched in LOX-1-expressing ImN subsets and in antimicrobial neutrophil factors. A validation study (118 patients, second pandemic wave) confirmed and strengthened the association of the proportion of ImN subsets with disease severity, invasive ventilation, and death. Only high proportions of LOX-1-expressing ImNs remained strongly associated with a high risk of severe thrombosis independently of the plasma antimicrobial neutrophil factors, suggesting an independent association of ImN markers with their functions.

Conclusion:

LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Scavenger Receptors, Class E / COVID-19 / Neutrophils Type of study: Etiology study / Prognostic study / Risk factors Topics: Long Covid Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.752612

Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Scavenger Receptors, Class E / COVID-19 / Neutrophils Type of study: Etiology study / Prognostic study / Risk factors Topics: Long Covid Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.752612