Evidence map›Paper›PMID 33441124›Full record

ArticleGenome medicine2021

Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.

Anna C Aschenbrenner, Maria Mouktaroudi, Benjamin Krämer, Marie Oestreich, Nikolaos Antonakos, Melanie Nuesch-Germano, Konstantina Gkizeli, Lorenzo Bonaguro, Nico Reusch, Kevin Baßler and 46 more

Abstract read
In one paragraph

Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

180 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. Early Fc-effector antibody signatures impact COVID-19 disease trajectory.medRxiv : the preprint server for health sciences · 2026
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  18. NETosis: A key player in autoimmunity, COVID-19, and long COVID.Journal of translational autoimmunity · 2025
    Review
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  20. Article

120 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

56 authors.

Anna C AschenbrennerSystems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Maria Mouktaroudi4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Benjamin KrämerDepartment I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
Marie OestreichGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Nikolaos Antonakos4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Melanie Nuesch-GermanoGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Konstantina Gkizeli4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Lorenzo BonaguroGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Nico ReuschGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Kevin BaßlerGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Maria Saridaki4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Rainer KnollGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Tal PechtGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Theodore S KapellosGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Sarandia DoulouGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Charlotte KrögerGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Miriam HerbertGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Lisa HolstenGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Arik HorneGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Ioanna D GemündGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Nikoletta Rovina1st Department of Pulmonary Medicine and Intensive Care Unit, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Shobhit AgrawalWest German Genome Center (WGGC), University of Bonn, Bonn, Germany.
Kilian DahmGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Martina van UelftGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Anna DrewsPRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
Lena LenkeitGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Niklas BruseDepartment of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Jelle GerretsenDepartment of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Jannik GierlichGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Matthias BeckerPRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
Kristian HändlerPRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
Michael KrautPRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
Heidi TheisPRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
Simachew MengisteGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Elena De DomenicoPRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
Jonas Schulte-SchreppingGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Lea SeepGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Jan RaabeDepartment I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
Christoph HoffmeisterDepartment I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
Michael ToVinhDepartment I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
Verena KeitelDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Gereon RiekeDepartment I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
Valentina TaleviPopulation Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Dirk SkowaschDepartment of Internal Medicine II, Section of Pneumology, University Hospital of Bonn (UKB), Bonn, Germany.
N Ahmad AzizPopulation Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Peter PickkersDepartment of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Frank L van de VeerdonkDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Mihai G NeteaDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Joachim L SchultzeSystems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Matthijs KoxDepartment of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Monique M B BretelerPopulation Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Jacob NattermannDepartment I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
Antonia Koutsoukou1st Department of Pulmonary Medicine and Intensive Care Unit, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Evangelos J Giamarellos-Bourboulis4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Thomas UlasSystems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. t.ulas@uni-bonn.de.ORCID 0000-0002-9785-4197
German COVID-19 Omics Initiative (DeCOI)

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system.

methodsIn order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings.

resultsHere, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.

conclusionsOur study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

Indexed as

TranscriptomeAntiviral AgentsCase-Control StudiesCOVID-19COVID-19 Drug TreatmentDown-RegulationDrug RepositioningHumansNeutrophilsPhenotypePrincipal Component AnalysisRNASequence Analysis, RNASeverity of Illness IndexUp-RegulationAntiviral AgentsRNABlood transcriptomicsCo-expression analysisCOVID-19Drug repurposingGranulocytesMolecular disease phenotypesNeutrophilsStratificationTranscriptome

Identifiers

PMID33441124
PMCPMC7805430

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.