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

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 percent 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.