LOX-1+ immature neutrophils predict severe COVID-19 patients at risk of thrombotic complications

Combadiere, Béhazine; Adam, Lucille; 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

Rational Lymphopenia and neutrophil/lymphocyte ratio may have prognostic value in coronavirus disease 2019 (COVID-19) severity. Objective We sought to investigate the representation of neutrophil subsets in severe and critical COVID-19 patients based on Intensive Care Units (ICU) and non-ICU admission. Methods We developed a multi-parametric neutrophil profiling strategy based on known neutrophil markers to distinguish COVID-19 phenotypes in critical and severe patients. Results Our results showed that 80% of ICU patients develop strong myelemia with CD10−CD64+ immature neutrophils. Cellular profiling revealed two distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) or the Interleukin-3 receptor alpha (CD123), both significantly overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1-expressing immature neutrophils positively correlated with clinical severity, with the cytokine storm (IL-1β, IL-6, IL-8, TNFα), and with intravascular coagulation. Importantly, high proportions of LOX-1+-immature neutrophils are associated with high risks of severe thrombosis. Conclusions Together these data suggest that point of care enumeration of LOX-1-immature neutrophils might help distinguish patients at risk of thrombosis complication and most likely to benefit from intensified anticoagulant therapy.