TY  - JOUR
AU  - Aschenbrenner, Anna C
AU  - Mouktaroudi, Maria
AU  - Krämer, Benjamin
AU  - Oestreich, Marie
AU  - Antonakos, Nikolaos
AU  - Nuesch-Germano, Melanie
AU  - Gkizeli, Konstantina
AU  - Bonaguro, Lorenzo
AU  - Reusch, Nico
AU  - Baßler, Kevin
AU  - Saridaki, Maria
AU  - Knoll, Rainer
AU  - Pecht, Tal
AU  - Kapellos, Theodore S
AU  - Doulou, Sarandia
AU  - Kröger, Charlotte
AU  - Herbert, Miriam
AU  - Holsten, Lisa
AU  - Horne, Arik
AU  - Gemünd, Ioanna D
AU  - Rovina, Nikoletta
AU  - Agrawal, Shobhit
AU  - Dahm, Kilian
AU  - van Uelft, Martina
AU  - Drews, Anna
AU  - Lenkeit, Lena
AU  - Bruse, Niklas
AU  - Gerretsen, Jelle
AU  - Gierlich, Jannik
AU  - Becker, Matthias
AU  - Händler, Kristian
AU  - Kraut, Michael
AU  - Theis, Heidi
AU  - Mengiste, Simachew
AU  - De Domenico, Elena
AU  - Schulte-Schrepping, Jonas
AU  - Seep, Lea
AU  - Raabe, Jan
AU  - Hoffmeister, Christoph
AU  - ToVinh, Michael
AU  - Keitel, Verena
AU  - Rieke, Gereon
AU  - Talevi, Valentina
AU  - Skowasch, Dirk
AU  - Aziz, N Ahmad
AU  - Pickkers, Peter
AU  - van de Veerdonk, Frank L
AU  - Netea, Mihai G
AU  - Schultze, Joachim L
AU  - Kox, Matthijs
AU  - Breteler, Monique M B
AU  - Nattermann, Jacob
AU  - Koutsoukou, Antonia
AU  - Giamarellos-Bourboulis, Evangelos J
AU  - Ulas, Thomas
AU  - Altmüller, Janine
AU  - Angelov, Angel
AU  - Bals, Robert
AU  - Bartholomäus, Alexander
AU  - Becker, Anke
AU  - Bitzer, Michael
AU  - Bonifacio, Ezio
AU  - Bork, Peer
AU  - Casadei, Nicolas
AU  - Clavel, Thomas
AU  - Colome-Tatche, Maria
AU  - Diefenbach, Andreas
AU  - Dilthey, Alexander
AU  - Fischer, Nicole
AU  - Förstner, Konrad
AU  - Franzenburg, Sören
AU  - Frick, Julia-Stefanie
AU  - Gabernet, Gisela
AU  - Gagneur, Julien
AU  - Ganzenmüller, Tina
AU  - Göpel, Siri
AU  - Goesmann, Alexander
AU  - Hain, Torsten
AU  - Heimbach, André
AU  - Hummel, Michael
AU  - Iftner, Angelika
AU  - Iftner, Thomas
AU  - Janssen, Stefan
AU  - Kalinowski, Jörn
AU  - Kallies, René
AU  - Kehr, Birte
AU  - Keller, Andreas
AU  - Kim-Hellmuth, Sarah
AU  - Klein, Christoph
AU  - Kohlbacher, Oliver
AU  - Köhrer, Karl
AU  - Korbel, Jan
AU  - Kühnert, Denise
AU  - Kurth, Ingo
AU  - Landthaler, Markus
AU  - Li, Yang
AU  - Ludwig, Kerstin
AU  - Makarewicz, Oliwia
AU  - Marz, Manja
AU  - McHardy, Alice
AU  - Mertes, Christian
AU  - Nöthen, Markus
AU  - Nürnberg, Peter
AU  - Ohler, Uwe
AU  - Ossowski, Stephan
AU  - Overmann, Jörg
AU  - Pfeffer, Klaus
AU  - Poetsch, Anna R
AU  - Pühler, Alfred
AU  - Rajewsky, Nikolaus
AU  - Ralser, Markus
AU  - Rieß, Olaf
AU  - Ripke, Stephan
AU  - Nunes da Rocha, Ulisses
AU  - Rosenstiel, Philip
AU  - Saliba, Antoine-Emmanuel
AU  - Sander, Leif Erik
AU  - Sawitzki, Birgit
AU  - Schiffer, Philipp
AU  - Schneider, Wulf
AU  - Schulte, Eva-Christina
AU  - Schultze, Joachim L
AU  - Sczyrba, Alexander
AU  - Singh, Yogesh
AU  - Sonnabend, Michael
AU  - Stegle, Oliver
AU  - Stoye, Jens
AU  - Theis, Fabian
AU  - Vehreschild, Janne
AU  - Vogel, Jörg
AU  - von Kleist, Max
AU  - Walker, Andreas
AU  - Walter, Jörn
AU  - Wieczorek, Dagmar
AU  - Winkler, Sylke
AU  - Ziebuhr, John
TI  - Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.
JO  - Genome medicine
VL  - 13
IS  - 1
SN  - 1756-994X
CY  - London
PB  - BioMed Central
M1  - DKFZ-2021-03098
SP  - 7
PY  - 2021
AB  - 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.
KW  - Antiviral Agents: therapeutic use
KW  - COVID-19: drug therapy
KW  - COVID-19: pathology
KW  - COVID-19: virology
KW  - Case-Control Studies
KW  - Down-Regulation
KW  - Drug Repositioning
KW  - Humans
KW  - Neutrophils: cytology
KW  - Neutrophils: immunology
KW  - Neutrophils: metabolism
KW  - Phenotype
KW  - Principal Component Analysis
KW  - RNA: blood
KW  - RNA: chemistry
KW  - RNA: metabolism
KW  - Sequence Analysis, RNA
KW  - Severity of Illness Index
KW  - Transcriptome
KW  - Up-Regulation
KW  - Blood transcriptomics (Other)
KW  - COVID-19 (Other)
KW  - Co-expression analysis (Other)
KW  - Drug repurposing (Other)
KW  - Granulocytes (Other)
KW  - Molecular disease phenotypes (Other)
KW  - Neutrophils (Other)
KW  - Stratification (Other)
KW  - Transcriptome (Other)
KW  - Antiviral Agents (NLM Chemicals)
KW  - RNA (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:33441124
C2  - pmc:PMC7805430
DO  - DOI:10.1186/s13073-020-00823-5
UR  - https://inrepo02.dkfz.de/record/178091
ER  -