ArticleNature communications2021
Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.
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In one paragraph
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 6 pooled it
15.8field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
160 citing papers in PubMed, 6 syntheses or guidelines pooled it, 258 citations in OpenAlex.
- Systemic cytokines drive conserved severity-associated myeloid responses across bacterial and viral infections.Communications biology · 2025Pooled it
- Automated and reproducible cell identification in mass cytometry using neural networks.Briefings in bioinformatics · 2023Pooled it
- Biomarkers in long COVID-19: A systematic review.Frontiers in medicine · 2023Pooled it
- Identifying novel host-based diagnostic biomarker panels for COVID-19: a whole-blood/nasopharyngeal transcriptome meta-analysis.Molecular medicine (Cambridge, Mass.) · 2022Pooled it
- A composite ranking of risk factors for COVID-19 time-to-event data from a Turkish cohort.Computational biology and chemistry · 2022Pooled it
- Use of steroids in COVID-19 patients: A meta-analysis.European journal of pharmacology · 2022Pooled it
- Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19.Science advances · 2023Trial
- Complement blockade with eculizumab for treatment of severe Coronavirus Disease 2019 in pregnancy: A case series.American journal of reproductive immunology (New York, N.Y. : 1989) · 2022Trial
- Monocytes in pneumonia: Functional plasticity and innate memory (Review).International journal of molecular medicine · 2026Review
- Deconformer: efficient cell-type composition profiling of cfRNA across diverse cell types.Briefings in bioinformatics · 2026Article
- Neutrophil Extracellular Traps in Patients with Intracerebral Hemorrhage.Neurocritical care · 2026Article
- Complete Response of Merkel Cell Carcinoma to Immunotherapy and Single-Fraction Radiotherapy Following Severe COVID-19 Infection: A Case Report and Review of Immune Mechanism.The American surgeon · 2026Article
- Machine Learning Identification of Cell-Type-Specific Molecular Signatures Distinguishing COVID-19 from Other Lower Respiratory Tract Diseases.Life (Basel, Switzerland) · 2026Article
- STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation.JHEP reports : innovation in hepatology · 2026Article
- Transcriptome changes in circulating immune cells of critical COVID-19 patients predict a specific metabolic and epigenetic imprint.Journal of translational medicine · 2026Article
- scSurv: a deep generative model for single-cell survival analysis.Bioinformatics (Oxford, England) · 2026Article
- Comparative systemic pathogenicity and host tropism of ancestral SARS-CoV-2, Delta, and Omicron EG.5 variants in K18-hACE2 mice.Frontiers in immunology · 2026Article
- Biological Plausibility Between Long-COVID and Periodontal Disease Development or Progression.Biomedicines · 2025Review
- DNA methylation-based epigenetic clocks highlight immune-driven aging acceleration in COVID-19 across diverse populations.Biogerontology · 2025Article
- Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Patients With Subarachnoid Hemorrhage.Journal of the American Heart Association · 2025Article
100 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
55 authors at 4 institutions in 2 countries.
L Vanderbeke *Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-3364-1213
P Van Mol *Laboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.
Y Van Herck *Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-4604-8010
F De Smet *Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-6669-3335
S Humblet-Baron *Adaptive Immunology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
K Martinod *Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-1026-6107
A AntoranzLaboratory for Precision Cancer Medicine, Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
I ArijsLaboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-9415-083X
B BoeckxLaboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.
F M BosisioTranslational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
M CasaerLaboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
D DauweLaboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-9771-2543
W De WeverRadiology, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
C DoomsLaboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
E DreesenClinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-0785-2930
A EmmaneelDepartment of Applied Mathematics, Computer Science and Statistics, VIB-UGent Center for Inflammation Research, VIB-UGent, Gent, Belgium.ORCID http://orcid.org/0000-0003-4569-2330
J FiltjensLaboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.
M GouwyLaboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.
J GunstLaboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-2470-6393
G HermansLaboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
S JansenLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, B Leuven, Belgium.ORCID http://orcid.org/0000-0002-9344-131X
K LagrouLaboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
A ListonLaboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-6272-4085
N LorentDepartment of Pneumology, University Hospitals Leuven, Leuven, Belgium.
P MeerssemanLaboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
T MercierLaboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-1517-6426
J NeytsLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, B Leuven, Belgium.ORCID http://orcid.org/0000-0002-0033-7514
J OdentDepartment of Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
D PanovskaLaboratory for Precision Cancer Medicine, Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-0906-3860
P A PenttilaKU Leuven Flow & Mass Cytometry Facility, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-5861-4430
E PolletDepartment of Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
P ProostLaboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-0133-5545
J QianLaboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0001-6145-045X
K QuintelierDepartment of Applied Mathematics, Computer Science and Statistics, VIB-UGent Center for Inflammation Research, VIB-UGent, Gent, Belgium.ORCID http://orcid.org/0000-0001-5306-5615
J RaesLaboratory of Molecular Bacteriology (Rega Institute), Department of Microbiology, Immunology and Transplantation, KU Leuven, and VIB Center for Microbiology, Leuven, Belgium.ORCID http://orcid.org/0000-0002-1337-041X
S RexAnesthesiology and Algology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
Y SaeysDepartment of Applied Mathematics, Computer Science and Statistics, VIB-UGent Center for Inflammation Research, VIB-UGent, Gent, Belgium.ORCID http://orcid.org/0000-0002-0415-1506
J SprootenLaboratory for Cell Stress & Immunity (CSI), Department of Cellular and Molecular Medicine (CMM), KU Leuven, Leuven, Belgium.
S TejparMolecular Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.
D TestelmansLaboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
K ThevissenCentre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems (M2S), KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-0275-9072
T Van BuytenLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, B Leuven, Belgium.
J VandenhauteLaboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0001-9485-8806
S Van GassenDepartment of Applied Mathematics, Computer Science and Statistics, VIB-UGent Center for Inflammation Research, VIB-UGent, Gent, Belgium.ORCID http://orcid.org/0000-0002-7119-5330
L C Velásquez PereiraCentre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
R VosLaboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-3468-9251
B WeynandTranslational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
A WilmerLaboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
J YserbytLaboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
A D GargLaboratory for Cell Stress & Immunity (CSI), Department of Cellular and Molecular Medicine (CMM), KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-9976-9922
P MatthysLaboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-9685-6836
C WoutersAdaptive Immunology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
D LambrechtsLaboratory of Translational Genetics, Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-3429-302X
E WautersLaboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium. els.wauters@kuleuven.be.ORCID http://orcid.org/0000-0002-0115-0030
J WautersLaboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
KU Leuven · BERega Institute for Medical Research · BEVIB-UGent Center for Inflammation Research · BEBabraham Institute · GB
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
Neutrophil ActivationAgedAntigen-Presenting CellsCase-Control StudiesCOVID-19Cytokine Release SyndromeCytokinesExtracellular TrapsFemaleHistocompatibility Antigens Class IIHumansImmunophenotypingMaleMiddle AgedMonocytesSARS-CoV-2CytokinesHistocompatibility Antigens Class II
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