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@ARTICLE{Aschenbrenner:154641,
author = {Aschenbrenner, Anna C and Mouktaroudi, Maria and Krämer,
Benjamin and Oestreich, Marie and Antonakos, Nikolaos and
Nuesch-Germano, Melanie and Gkizeli, Konstantina and
Bonaguro, Lorenzo and Reusch, Nico and Baßler, Kevin and
Saridaki, Maria and Knoll, Rainer and Pecht, Tal and
Kapellos, Theodore S and Doulou, Sarandia and Kröger,
Charlotte and Herbert, Miriam and Holsten, Lisa and Horne,
Arik and Gemünd, Ioanna D and Rovina, Nikoletta and
Agrawal, Shobhit and Dahm, Kilian and van Uelft, Martina and
Drews, Anna and Lenkeit, Lena and Bruse, Niklas and
Gerretsen, Jelle and Gierlich, Jannik and Becker, Matthias
and Händler, Kristian and Kraut, Michael and Theis, Heidi
and Mengiste, Simachew and De Domenico, Elena and
Schulte-Schrepping, Jonas and Seep, Lea and Raabe, Jan and
Hoffmeister, Christoph and ToVinh, Michael and Keitel,
Verena and Rieke, Gereon and Talevi, Valentina and Skowasch,
Dirk and Aziz, N. Ahmad and Pickkers, Peter and van de
Veerdonk, Frank L and Netea, Mihai G and Schultze, Joachim L
and Kox, Matthijs and Breteler, Monique M B and Nattermann,
Jacob and Koutsoukou, Antonia and Giamarellos-Bourboulis,
Evangelos J and Ulas, Thomas and Altmüller, Janine and
Angelov, Angel and Bals, Robert and Bartholomäus, Alexander
and Becker, Anke and Bitzer, Michael and Bonifacio, Ezio and
Bork, Peer and Casadei, Nicolas and Clavel, Thomas and
Colome-Tatche, Maria and Diefenbach, Andreas and Dilthey,
Alexander and Fischer, Nicole and Förstner, Konrad and
Franzenburg, Sören and Frick, Julia-Stefanie and Gabernet,
Gisela and Gagneur, Julien and Ganzenmüller, Tina and
Göpel, Siri and Goesmann, Alexander and Hain, Torsten and
Heimbach, André and Hummel, Michael and Iftner, Angelika
and Iftner, Thomas and Janssen, Stefan and Kalinowski, Jörn
and Kallies, René and Kehr, Birte and Keller, Andreas and
Kim-Hellmuth, Sarah and Klein, Christoph and Kohlbacher,
Oliver and Köhrer, Karl and Korbel, Jan and Kühnert,
Denise and Kurth, Ingo and Landthaler, Markus and Li, Yang
and Ludwig, Kerstin and Makarewicz, Oliwia and Marz, Manja
and McHardy, Alice and Mertes, Christian and Nöthen, Markus
and Nürnberg, Peter and Ohler, Uwe and Ossowski, Stephan
and Overmann, Jörg and Pfeffer, Klaus and Poetsch, Anna R
and Pühler, Alfred and Rajewsky, Nikolaus and Ralser,
Markus and Rieß, Olaf and Ripke, Stephan and Nunes da
Rocha, Ulisses and Rosenstiel, Philip and Saliba,
Antoine-Emmanuel and Sander, Leif Erik and Sawitzki, Birgit
and Schiffer, Philipp and Schneider, Wulf and Schulte,
Eva-Christina and Schultze, Joachim L and Sczyrba, Alexander
and Singh, Yogesh and Sonnabend, Michael and Stegle, Oliver
and Stoye, Jens and Theis, Fabian and Vehreschild, Janne and
Vogel, Jörg and von Kleist, Max and Walker, Andreas and
Walter, Jörn and Wieczorek, Dagmar and Winkler, Sylke and
Ziebuhr, John},
collaboration = {Initiative, German COVID-19 Omics},
title = {{D}isease severity-specific neutrophil signatures in blood
transcriptomes stratify {COVID}-19 patients.},
journal = {Genome medicine},
volume = {13},
number = {1},
issn = {1756-994X},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2021-00289},
pages = {7},
year = {2021},
abstract = {The 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.In 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.Here, 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.Our 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.},
keywords = {Antiviral Agents: therapeutic use / COVID-19: drug therapy
/ COVID-19: pathology / COVID-19: virology / Case-Control
Studies / Down-Regulation / Drug Repositioning / Humans /
Neutrophils: cytology / Neutrophils: immunology /
Neutrophils: metabolism / Phenotype / Principal Component
Analysis / RNA: blood / RNA: chemistry / RNA: metabolism /
Sequence Analysis, RNA / Severity of Illness Index /
Transcriptome / Up-Regulation / Blood transcriptomics
(Other) / COVID-19 (Other) / Co-expression analysis (Other)
/ Drug repurposing (Other) / Granulocytes (Other) /
Molecular disease phenotypes (Other) / Neutrophils (Other) /
Stratification (Other) / Transcriptome (Other) / Antiviral
Agents (NLM Chemicals) / RNA (NLM Chemicals)},
cin = {Schultze - PRECISE / AG Schultze / AG Breteler / AG Aziz},
ddc = {610},
cid = {I:(DE-2719)1013031 / I:(DE-2719)1013038 /
I:(DE-2719)1012001 / I:(DE-2719)5000071},
pnm = {352 - Disease Mechanisms (POF4-352) / 354 - Disease
Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-354},
experiment = {EXP:(DE-2719)PRECISE-20190321 / EXP:(DE-2719)Rhineland
Study-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33441124},
pmc = {pmc:PMC7805430},
doi = {10.1186/s13073-020-00823-5},
url = {https://pub.dzne.de/record/154641},
}
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