Clinical & Translational Immunology (Jan 2021)
Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019
- Mieke Metzemaekers,
- Seppe Cambier,
- Marfa Blanter,
- Jennifer Vandooren,
- Ana Carolina deCarvalho,
- Bert Malengier‐Devlies,
- Lore Vanderbeke,
- Cato Jacobs,
- Sofie Coenen,
- Erik Martens,
- Noëmie Pörtner,
- Lotte Vanbrabant,
- Pierre Van Mol,
- Yannick Van Herck,
- Nathalie Van Aerde,
- Greet Hermans,
- Jan Gunst,
- Alexandre Borin,
- Bruna Toledo N Pereira,
- Arilson Bernardo dosSP Gomes,
- Stéfanie Primon Muraro,
- Gabriela Fabiano de Souza,
- Alessandro S Farias,
- José Luiz Proenca‐Modena,
- Marco Aurélio R Vinolo,
- the CONTAGIOUS Consortium,
- Pedro Elias Marques,
- Carine Wouters,
- Els Wauters,
- Sofie Struyf,
- Patrick Matthys,
- Ghislain Opdenakker,
- Rafael Elias Marques,
- Joost Wauters,
- Mieke Gouwy,
- Paul Proost
Affiliations
- Mieke Metzemaekers
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Seppe Cambier
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Marfa Blanter
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Jennifer Vandooren
- Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Ana Carolina deCarvalho
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Bert Malengier‐Devlies
- Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Lore Vanderbeke
- Laboratory of Clinical Bacteriology and Mycology Department of Microbiology, Immunology and Transplantation KU Leuven Leuven Belgium
- Cato Jacobs
- Laboratory for Clinical Infectious and Inflammatory Disorders Department of Microbiology, Immunology and Transplantation KU Leuven Leuven Belgium
- Sofie Coenen
- Division of Pediatrics University Hospitals Leuven Leuven Belgium
- Erik Martens
- Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Noëmie Pörtner
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Lotte Vanbrabant
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Pierre Van Mol
- Laboratory of Translational Genetics Department of Human Genetics VIB‐KU Leuven Leuven Belgium
- Yannick Van Herck
- Laboratory of Experimental Oncology Department of Oncology KU Leuven Leuven Belgium
- Nathalie Van Aerde
- Laboratory of Intensive Care Medicine Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium
- Greet Hermans
- Laboratory of Intensive Care Medicine Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium
- Jan Gunst
- Laboratory of Intensive Care Medicine Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium
- Alexandre Borin
- Brazilian Center for Research in Energy and Materials ‐ CNPEMBrazilian Biosciences National Laboratory Campinas LNBio Brazil
- Bruna Toledo N Pereira
- Laboratory of Immunoinflammation Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil
- Arilson Bernardo dosSP Gomes
- Laboratory of Immunoinflammation Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil
- Stéfanie Primon Muraro
- Laboratory Emerging Viruses Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil
- Gabriela Fabiano de Souza
- Laboratory Emerging Viruses Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil
- Alessandro S Farias
- Experimental Medicine Research Cluster (EMRC) University of Campinas (UNICAMP) Campinas Brazil
- José Luiz Proenca‐Modena
- Laboratory Emerging Viruses Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil
- Marco Aurélio R Vinolo
- Laboratory of Immunoinflammation Department of Genetics, Microbiology and Immunology Institute of Biology University of Campinas (UNICAMP) Campinas Brazil
- the CONTAGIOUS Consortium
- Pedro Elias Marques
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Carine Wouters
- Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Els Wauters
- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE) Department of Chronic Diseases and Metabolism KU Leuven Leuven Belgium
- Sofie Struyf
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Patrick Matthys
- Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Ghislain Opdenakker
- Laboratory of Immunobiology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Rafael Elias Marques
- Brazilian Center for Research in Energy and Materials ‐ CNPEMBrazilian Biosciences National Laboratory Campinas LNBio Brazil
- Joost Wauters
- Laboratory for Clinical Infectious and Inflammatory Disorders Department of Microbiology, Immunology and Transplantation KU Leuven Leuven Belgium
- Mieke Gouwy
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- Paul Proost
- Laboratory of Molecular Immunology Department of Microbiology, Immunology and Transplantation Rega Institute, KU Leuven Leuven Belgium
- DOI
- https://doi.org/10.1002/cti2.1271
- Journal volume & issue
-
Vol. 10,
no. 4
pp. n/a – n/a
Abstract
Abstract 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.
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