TY - JOUR
T1 - Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019
AU - CONTAGIOUS Consortium
AU - Metzemaekers, Mieke
AU - Cambier, Seppe
AU - Blanter, Marfa
AU - Vandooren, Jennifer
AU - de Carvalho, Ana Carolina
AU - Malengier-Devlies, Bert
AU - Vanderbeke, Lore
AU - Jacobs, Cato
AU - Coenen, Sofie
AU - Martens, Erik
AU - Pörtner, Noëmie
AU - Vanbrabant, Lotte
AU - Van Mol, Pierre
AU - Van Herck, Yannick
AU - Van Aerde, Nathalie
AU - Hermans, Greet
AU - Gunst, Jan
AU - Borin, Alexandre
AU - Toledo N Pereira, Bruna
AU - Dos Sp Gomes, Arilson Bernardo
AU - Primon Muraro, Stéfanie
AU - Fabiano de Souza, Gabriela
AU - S Farias, Alessandro
AU - Proenca-Modena, José Luiz
AU - R Vinolo, Marco Aurélio
AU - Marques, Pedro Elias
AU - Wouters, Carine
AU - Wauters, Els
AU - Struyf, Sofie
AU - Matthys, Patrick
AU - Opdenakker, Ghislain
AU - Marques, Rafael Elias
AU - Wauters, Joost
AU - Gouwy, Mieke
AU - Proost, Paul
N1 - © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
PY - 2021
Y1 - 2021
N2 - OBJECTIVES: Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation.METHODS: Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co-culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) allowed us to investigate viral replication in neutrophils.RESULTS: Upon ICU admission, patients displayed high plasma concentrations of granulocyte-colony-stimulating factor (G-CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10-, immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non-metalloproteinase-derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID-19 neutrophils were hyper-responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS-CoV-2 failed to replicate inside human neutrophils.CONCLUSION: Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID-19 patients, and supports the concept of an increased neutrophil activation state in the circulation.
AB - OBJECTIVES: Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation.METHODS: Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co-culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) allowed us to investigate viral replication in neutrophils.RESULTS: Upon ICU admission, patients displayed high plasma concentrations of granulocyte-colony-stimulating factor (G-CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10-, immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non-metalloproteinase-derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID-19 neutrophils were hyper-responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS-CoV-2 failed to replicate inside human neutrophils.CONCLUSION: Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID-19 patients, and supports the concept of an increased neutrophil activation state in the circulation.
U2 - 10.1002/cti2.1271
DO - 10.1002/cti2.1271
M3 - Article
C2 - 33968405
SN - 2050-0068
VL - 10
SP - e1271
JO - Clinical & translational immunology
JF - Clinical & translational immunology
IS - 4
ER -