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-1β, 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.
【저자키워드】 COVID-19, Neutrophils, Infectious diseases, thrombosis, Innate immunity, 【초록키워드】 ARDS, Cytokine storm, pandemic, Clinical characteristics, IL-6, severity, disease severity, neutrophil, intensive care unit, COVID-19 severity, invasive ventilation, ICU, CD10, PD-L1, BAL, Patient, Factors, death, IL-8, complications, Alpha, plasma, receptor, Critical, patients, function, Blood, association, acute respiratory distress, marker, Clinical severity, IL-1β, Bronchoalveolar lavage, COVID-19 patient, Cytometry, high risk, Prognostic value, syndrome, severe COVID-19 patients, help, TNFα, validation study, functions, non-ICU patients, CD64, objective, ICU patient, independent, Result, develop, proportion, investigated, remained, expressing, subset, oxidized, CD123, immature neutrophil, patients with ARDS, positively correlated, 【제목키워드】 Complication,