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

Combadiere, B.; Adam, L.; Quentric, P.; Rosenbaum, P.; Dorgham, K.; Bonduelle, O.; Parizot, C.; Sauce, D.; Mayaux, J.; Luyt, C.-E.; Boissonnas, A.; Amoura, Z.; Pourcher, V.; Miyara, M.; Gorochov, G.; Guihot, A.; Combadiere, C.

doi:10.1101/2020.09.15.293100

bioRxiv · 10.1101/2020.09.15.293100

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

Combadiere, B.·Adam, L.·Quentric, P.·Rosenbaum, P.·Dorgham, K.·Bonduelle, O.·Parizot, C.·Sauce, D.·Mayaux, J.·Luyt, C.-E.·Boissonnas, A.·Amoura, Z.·Pourcher, V.·Miyara, M.·Gorochov, G.·Guihot, A.·Combadiere, C.

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Abstract

RationalLymphopenia and neutrophil/lymphocyte ratio may have prognostic value in coronavirus disease 2019 (COVID-19) severity. ObjectiveWe 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. MethodsWe developed a multi-parametric neutrophil profiling strategy based on known neutrophil markers to distinguish COVID-19 phenotypes in critical and severe patients. ResultsOur 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-1{beta}, IL-6, IL-8, TNF), and with intravascular coagulation. Importantly, high proportions of LOX-1+-immature neutrophils are associated with high risks of severe thrombosis. ConclusionsTogether 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.

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Combadiere, B., Adam, L., Quentric, P., Rosenbaum, P., Dorgham, K., Bonduelle, O., Parizot, C., Sauce, D., Mayaux, J., Luyt, C.-E., Boissonnas, A., Amoura, Z., Pourcher, V., Miyara, M., Gorochov, G., Guihot, A., Combadiere, C.. 2020-09-15. LOX-1+ immature neutrophils predict severe COVID-19 patients at risk of thrombotic complications. https://doi.org/10.1101/2020.09.15.293100

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