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Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.
Vanderbeke, L; Van Mol, P; Van Herck, Y; De Smet, F; Humblet-Baron, S; Martinod, K; Antoranz, A; Arijs, I; Boeckx, B; Bosisio, F M; Casaer, M; Dauwe, D; De Wever, W; Dooms, C; Dreesen, E; Emmaneel, A; Filtjens, J; Gouwy, M; Gunst, J; Hermans, G; Jansen, S; Lagrou, K; Liston, A; Lorent, N; Meersseman, P; Mercier, T; Neyts, J; Odent, J; Panovska, D; Penttila, P A; Pollet, E; Proost, P; Qian, J; Quintelier, K; Raes, J; Rex, S; Saeys, Y; Sprooten, J; Tejpar, S; Testelmans, D; Thevissen, K; Van Buyten, T; Vandenhaute, J; Van Gassen, S; Velásquez Pereira, L C; Vos, R; Weynand, B; Wilmer, A; Yserbyt, J; Garg, A D.
  • Vanderbeke L; Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • Van Mol P; Laboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.
  • Van Herck Y; Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.
  • De Smet F; Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
  • Humblet-Baron S; Adaptive Immunology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • Martinod K; Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
  • Antoranz A; Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
  • Arijs I; Laboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.
  • Boeckx B; Laboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.
  • Bosisio FM; Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
  • Casaer M; Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
  • Dauwe D; Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
  • De Wever W; Radiology, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
  • Dooms C; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
  • Dreesen E; Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
  • Emmaneel A; Department of Applied Mathematics, Computer Science and Statistics, VIB-UGent Center for Inflammation Research, VIB-UGent, Gent, Belgium.
  • Filtjens J; Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.
  • Gouwy M; Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.
  • Gunst J; Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
  • Hermans G; Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
  • Jansen S; Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, B Leuven, Belgium.
  • Lagrou K; Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • Liston A; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
  • Lorent N; Department of Pneumology, University Hospitals Leuven, Leuven, Belgium.
  • Meersseman P; Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • Mercier T; Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • Neyts J; Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, B Leuven, Belgium.
  • Odent J; Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
  • Panovska D; Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
  • Penttila PA; KU Leuven Flow & Mass Cytometry Facility, KU Leuven, Leuven, Belgium.
  • Pollet E; Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
  • Proost P; Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.
  • Qian J; Laboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.
  • Quintelier K; Department of Applied Mathematics, Computer Science and Statistics, VIB-UGent Center for Inflammation Research, VIB-UGent, Gent, Belgium.
  • Raes J; Laboratory of Molecular Bacteriology (Rega Institute), Department of Microbiology, Immunology and Transplantation, KU Leuven, and VIB Center for Microbiology, Leuven, Belgium.
  • Rex S; Anesthesiology and Algology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
  • Saeys Y; Department of Applied Mathematics, Computer Science and Statistics, VIB-UGent Center for Inflammation Research, VIB-UGent, Gent, Belgium.
  • Sprooten J; Laboratory for Cell Stress & Immunity (CSI), Department of Cellular and Molecular Medicine (CMM), KU Leuven, Leuven, Belgium.
  • Tejpar S; Molecular Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.
  • Testelmans D; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
  • Thevissen K; Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems (M2S), KU Leuven, Leuven, Belgium.
  • Van Buyten T; Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, B Leuven, Belgium.
  • Vandenhaute J; Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.
  • Van Gassen S; Department of Applied Mathematics, Computer Science and Statistics, VIB-UGent Center for Inflammation Research, VIB-UGent, Gent, Belgium.
  • Velásquez Pereira LC; Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
  • Vos R; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
  • Weynand B; Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
  • Wilmer A; Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • Yserbyt J; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
  • Garg AD; Laboratory for Cell Stress & Immunity (CSI), Department of Cellular and Molecular Medicine (CMM), KU Leuven, Leuven, Belgium.
Nat Commun ; 12(1): 4117, 2021 07 05.
Article in English | MEDLINE | ID: covidwho-1297301
ABSTRACT
Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Monocytes / Neutrophil Activation / Cytokine Release Syndrome / COVID-19 Type of study: Observational study / Prognostic study Topics: Long Covid Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-24360-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Monocytes / Neutrophil Activation / Cytokine Release Syndrome / COVID-19 Type of study: Observational study / Prognostic study Topics: Long Covid Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-24360-w