000154641 001__ 154641
000154641 005__ 20240612120602.0
000154641 0247_ $$2doi$$a10.1186/s13073-020-00823-5
000154641 0247_ $$2pmid$$apmid:33441124
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000154641 037__ $$aDZNE-2021-00289
000154641 041__ $$aEnglish
000154641 082__ $$a610
000154641 1001_ $$0P:(DE-2719)2812913$$aAschenbrenner, Anna C$$b0$$eFirst author
000154641 245__ $$aDisease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.
000154641 260__ $$aLondon$$bBioMed Central$$c2021
000154641 3367_ $$2DRIVER$$aarticle
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000154641 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1718105474_5894
000154641 3367_ $$2BibTeX$$aARTICLE
000154641 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000154641 3367_ $$00$$2EndNote$$aJournal Article
000154641 520__ $$aThe 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.
000154641 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000154641 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x1
000154641 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000154641 650_7 $$2Other$$aBlood transcriptomics
000154641 650_7 $$2Other$$aCOVID-19
000154641 650_7 $$2Other$$aCo-expression analysis
000154641 650_7 $$2Other$$aDrug repurposing
000154641 650_7 $$2Other$$aGranulocytes
000154641 650_7 $$2Other$$aMolecular disease phenotypes
000154641 650_7 $$2Other$$aNeutrophils
000154641 650_7 $$2Other$$aStratification
000154641 650_7 $$2Other$$aTranscriptome
000154641 650_7 $$2NLM Chemicals$$aAntiviral Agents
000154641 650_7 $$063231-63-0$$2NLM Chemicals$$aRNA
000154641 650_2 $$2MeSH$$aAntiviral Agents: therapeutic use
000154641 650_2 $$2MeSH$$aCOVID-19: drug therapy
000154641 650_2 $$2MeSH$$aCOVID-19: pathology
000154641 650_2 $$2MeSH$$aCOVID-19: virology
000154641 650_2 $$2MeSH$$aCase-Control Studies
000154641 650_2 $$2MeSH$$aDown-Regulation
000154641 650_2 $$2MeSH$$aDrug Repositioning
000154641 650_2 $$2MeSH$$aHumans
000154641 650_2 $$2MeSH$$aNeutrophils: cytology
000154641 650_2 $$2MeSH$$aNeutrophils: immunology
000154641 650_2 $$2MeSH$$aNeutrophils: metabolism
000154641 650_2 $$2MeSH$$aPhenotype
000154641 650_2 $$2MeSH$$aPrincipal Component Analysis
000154641 650_2 $$2MeSH$$aRNA: blood
000154641 650_2 $$2MeSH$$aRNA: chemistry
000154641 650_2 $$2MeSH$$aRNA: metabolism
000154641 650_2 $$2MeSH$$aSequence Analysis, RNA
000154641 650_2 $$2MeSH$$aSeverity of Illness Index
000154641 650_2 $$2MeSH$$aTranscriptome
000154641 650_2 $$2MeSH$$aUp-Regulation
000154641 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
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000154641 7001_ $$0P:(DE-HGF)0$$aMouktaroudi, Maria$$b1
000154641 7001_ $$0P:(DE-HGF)0$$aKrämer, Benjamin$$b2
000154641 7001_ $$0P:(DE-HGF)0$$aOestreich, Marie$$b3
000154641 7001_ $$0P:(DE-HGF)0$$aAntonakos, Nikolaos$$b4
000154641 7001_ $$0P:(DE-HGF)0$$aNuesch-Germano, Melanie$$b5
000154641 7001_ $$0P:(DE-HGF)0$$aGkizeli, Konstantina$$b6
000154641 7001_ $$0P:(DE-HGF)0$$aBonaguro, Lorenzo$$b7
000154641 7001_ $$0P:(DE-HGF)0$$aReusch, Nico$$b8
000154641 7001_ $$0P:(DE-HGF)0$$aBaßler, Kevin$$b9
000154641 7001_ $$0P:(DE-HGF)0$$aSaridaki, Maria$$b10
000154641 7001_ $$0P:(DE-HGF)0$$aKnoll, Rainer$$b11
000154641 7001_ $$0P:(DE-HGF)0$$aPecht, Tal$$b12
000154641 7001_ $$0P:(DE-HGF)0$$aKapellos, Theodore S$$b13
000154641 7001_ $$0P:(DE-HGF)0$$aDoulou, Sarandia$$b14
000154641 7001_ $$0P:(DE-HGF)0$$aKröger, Charlotte$$b15
000154641 7001_ $$0P:(DE-HGF)0$$aHerbert, Miriam$$b16
000154641 7001_ $$0P:(DE-HGF)0$$aHolsten, Lisa$$b17
000154641 7001_ $$0P:(DE-HGF)0$$aHorne, Arik$$b18
000154641 7001_ $$0P:(DE-HGF)0$$aGemünd, Ioanna D$$b19
000154641 7001_ $$0P:(DE-HGF)0$$aRovina, Nikoletta$$b20
000154641 7001_ $$0P:(DE-HGF)0$$aAgrawal, Shobhit$$b21
000154641 7001_ $$0P:(DE-HGF)0$$aDahm, Kilian$$b22
000154641 7001_ $$0P:(DE-HGF)0$$avan Uelft, Martina$$b23
000154641 7001_ $$0P:(DE-2719)2812302$$aDrews, Anna$$b24
000154641 7001_ $$0P:(DE-HGF)0$$aLenkeit, Lena$$b25
000154641 7001_ $$0P:(DE-HGF)0$$aBruse, Niklas$$b26
000154641 7001_ $$0P:(DE-HGF)0$$aGerretsen, Jelle$$b27
000154641 7001_ $$0P:(DE-HGF)0$$aGierlich, Jannik$$b28
000154641 7001_ $$0P:(DE-2719)2812750$$aBecker, Matthias$$b29
000154641 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b30
000154641 7001_ $$0P:(DE-2719)9000840$$aKraut, Michael$$b31
000154641 7001_ $$0P:(DE-2719)2812165$$aTheis, Heidi$$b32
000154641 7001_ $$0P:(DE-HGF)0$$aMengiste, Simachew$$b33
000154641 7001_ $$0P:(DE-2719)9000846$$aDe Domenico, Elena$$b34
000154641 7001_ $$0P:(DE-HGF)0$$aSchulte-Schrepping, Jonas$$b35
000154641 7001_ $$0P:(DE-HGF)0$$aSeep, Lea$$b36
000154641 7001_ $$0P:(DE-HGF)0$$aRaabe, Jan$$b37
000154641 7001_ $$0P:(DE-HGF)0$$aHoffmeister, Christoph$$b38
000154641 7001_ $$0P:(DE-HGF)0$$aToVinh, Michael$$b39
000154641 7001_ $$0P:(DE-HGF)0$$aKeitel, Verena$$b40
000154641 7001_ $$0P:(DE-HGF)0$$aRieke, Gereon$$b41
000154641 7001_ $$0P:(DE-2719)9001002$$aTalevi, Valentina$$b42
000154641 7001_ $$0P:(DE-HGF)0$$aSkowasch, Dirk$$b43
000154641 7001_ $$0P:(DE-2719)2812578$$aAziz, N. Ahmad$$b44$$udzne
000154641 7001_ $$0P:(DE-HGF)0$$aPickkers, Peter$$b45
000154641 7001_ $$0P:(DE-HGF)0$$avan de Veerdonk, Frank L$$b46
000154641 7001_ $$0P:(DE-HGF)0$$aNetea, Mihai G$$b47
000154641 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b48
000154641 7001_ $$0P:(DE-HGF)0$$aKox, Matthijs$$b49
000154641 7001_ $$0P:(DE-2719)2810403$$aBreteler, Monique M B$$b50
000154641 7001_ $$0P:(DE-HGF)0$$aNattermann, Jacob$$b51
000154641 7001_ $$0P:(DE-HGF)0$$aKoutsoukou, Antonia$$b52
000154641 7001_ $$0P:(DE-HGF)0$$aGiamarellos-Bourboulis, Evangelos J$$b53
000154641 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b54$$eLast author
000154641 7001_ $$0P:(DE-HGF)0$$aInitiative, German COVID-19 Omics$$b55$$eCollaboration Author
000154641 7001_ $$0P:(DE-HGF)0$$aAltmüller, Janine$$b56
000154641 7001_ $$0P:(DE-HGF)0$$aAngelov, Angel$$b57
000154641 7001_ $$0P:(DE-HGF)0$$aBals, Robert$$b58
000154641 7001_ $$0P:(DE-HGF)0$$aBartholomäus, Alexander$$b59
000154641 7001_ $$0P:(DE-HGF)0$$aBecker, Anke$$b60
000154641 7001_ $$0P:(DE-HGF)0$$aBitzer, Michael$$b61
000154641 7001_ $$0P:(DE-HGF)0$$aBonifacio, Ezio$$b62
000154641 7001_ $$0P:(DE-HGF)0$$aBork, Peer$$b63
000154641 7001_ $$0P:(DE-HGF)0$$aCasadei, Nicolas$$b64
000154641 7001_ $$0P:(DE-HGF)0$$aClavel, Thomas$$b65
000154641 7001_ $$0P:(DE-HGF)0$$aColome-Tatche, Maria$$b66
000154641 7001_ $$0P:(DE-HGF)0$$aDiefenbach, Andreas$$b67
000154641 7001_ $$0P:(DE-HGF)0$$aDilthey, Alexander$$b68
000154641 7001_ $$0P:(DE-HGF)0$$aFischer, Nicole$$b69
000154641 7001_ $$0P:(DE-HGF)0$$aFörstner, Konrad$$b70
000154641 7001_ $$0P:(DE-HGF)0$$aFranzenburg, Sören$$b71
000154641 7001_ $$0P:(DE-HGF)0$$aFrick, Julia-Stefanie$$b72
000154641 7001_ $$0P:(DE-HGF)0$$aGabernet, Gisela$$b73
000154641 7001_ $$0P:(DE-HGF)0$$aGagneur, Julien$$b74
000154641 7001_ $$0P:(DE-HGF)0$$aGanzenmüller, Tina$$b75
000154641 7001_ $$0P:(DE-HGF)0$$aGöpel, Siri$$b76
000154641 7001_ $$0P:(DE-HGF)0$$aGoesmann, Alexander$$b77
000154641 7001_ $$0P:(DE-HGF)0$$aHain, Torsten$$b78
000154641 7001_ $$0P:(DE-HGF)0$$aHeimbach, André$$b79
000154641 7001_ $$0P:(DE-HGF)0$$aHummel, Michael$$b80
000154641 7001_ $$0P:(DE-HGF)0$$aIftner, Angelika$$b81
000154641 7001_ $$0P:(DE-HGF)0$$aIftner, Thomas$$b82
000154641 7001_ $$0P:(DE-HGF)0$$aJanssen, Stefan$$b83
000154641 7001_ $$0P:(DE-HGF)0$$aKalinowski, Jörn$$b84
000154641 7001_ $$0P:(DE-HGF)0$$aKallies, René$$b85
000154641 7001_ $$0P:(DE-HGF)0$$aKehr, Birte$$b86
000154641 7001_ $$0P:(DE-HGF)0$$aKeller, Andreas$$b87
000154641 7001_ $$0P:(DE-HGF)0$$aKim-Hellmuth, Sarah$$b88
000154641 7001_ $$0P:(DE-HGF)0$$aKlein, Christoph$$b89
000154641 7001_ $$0P:(DE-HGF)0$$aKohlbacher, Oliver$$b90
000154641 7001_ $$0P:(DE-HGF)0$$aKöhrer, Karl$$b91
000154641 7001_ $$0P:(DE-HGF)0$$aKorbel, Jan$$b92
000154641 7001_ $$0P:(DE-HGF)0$$aKühnert, Denise$$b93
000154641 7001_ $$0P:(DE-HGF)0$$aKurth, Ingo$$b94
000154641 7001_ $$0P:(DE-HGF)0$$aLandthaler, Markus$$b95
000154641 7001_ $$0P:(DE-HGF)0$$aLi, Yang$$b96
000154641 7001_ $$0P:(DE-HGF)0$$aLudwig, Kerstin$$b97
000154641 7001_ $$0P:(DE-HGF)0$$aMakarewicz, Oliwia$$b98
000154641 7001_ $$0P:(DE-HGF)0$$aMarz, Manja$$b99
000154641 7001_ $$0P:(DE-HGF)0$$aMcHardy, Alice$$b100
000154641 7001_ $$0P:(DE-HGF)0$$aMertes, Christian$$b101
000154641 7001_ $$0P:(DE-HGF)0$$aNöthen, Markus$$b102
000154641 7001_ $$0P:(DE-HGF)0$$aNürnberg, Peter$$b103
000154641 7001_ $$0P:(DE-HGF)0$$aOhler, Uwe$$b104
000154641 7001_ $$0P:(DE-HGF)0$$aOssowski, Stephan$$b105
000154641 7001_ $$0P:(DE-HGF)0$$aOvermann, Jörg$$b106
000154641 7001_ $$0P:(DE-HGF)0$$aPfeffer, Klaus$$b107
000154641 7001_ $$0P:(DE-HGF)0$$aPoetsch, Anna R$$b108
000154641 7001_ $$0P:(DE-HGF)0$$aPühler, Alfred$$b109
000154641 7001_ $$0P:(DE-HGF)0$$aRajewsky, Nikolaus$$b110
000154641 7001_ $$0P:(DE-HGF)0$$aRalser, Markus$$b111
000154641 7001_ $$0P:(DE-HGF)0$$aRieß, Olaf$$b112
000154641 7001_ $$0P:(DE-HGF)0$$aRipke, Stephan$$b113
000154641 7001_ $$0P:(DE-HGF)0$$aNunes da Rocha, Ulisses$$b114
000154641 7001_ $$0P:(DE-HGF)0$$aRosenstiel, Philip$$b115
000154641 7001_ $$0P:(DE-HGF)0$$aSaliba, Antoine-Emmanuel$$b116
000154641 7001_ $$0P:(DE-HGF)0$$aSander, Leif Erik$$b117
000154641 7001_ $$0P:(DE-HGF)0$$aSawitzki, Birgit$$b118
000154641 7001_ $$0P:(DE-HGF)0$$aSchiffer, Philipp$$b119
000154641 7001_ $$0P:(DE-HGF)0$$aSchneider, Wulf$$b120
000154641 7001_ $$0P:(DE-HGF)0$$aSchulte, Eva-Christina$$b121
000154641 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b122
000154641 7001_ $$0P:(DE-HGF)0$$aSczyrba, Alexander$$b123
000154641 7001_ $$0P:(DE-HGF)0$$aSingh, Yogesh$$b124
000154641 7001_ $$0P:(DE-HGF)0$$aSonnabend, Michael$$b125
000154641 7001_ $$0P:(DE-HGF)0$$aStegle, Oliver$$b126
000154641 7001_ $$0P:(DE-HGF)0$$aStoye, Jens$$b127
000154641 7001_ $$0P:(DE-HGF)0$$aTheis, Fabian$$b128
000154641 7001_ $$0P:(DE-HGF)0$$aVehreschild, Janne$$b129
000154641 7001_ $$0P:(DE-HGF)0$$aVogel, Jörg$$b130
000154641 7001_ $$0P:(DE-HGF)0$$avon Kleist, Max$$b131
000154641 7001_ $$0P:(DE-HGF)0$$aWalker, Andreas$$b132
000154641 7001_ $$0P:(DE-HGF)0$$aWalter, Jörn$$b133
000154641 7001_ $$0P:(DE-HGF)0$$aWieczorek, Dagmar$$b134
000154641 7001_ $$0P:(DE-HGF)0$$aWinkler, Sylke$$b135
000154641 7001_ $$0P:(DE-HGF)0$$aZiebuhr, John$$b136
000154641 773__ $$0PERI:(DE-600)2484394-5$$a10.1186/s13073-020-00823-5$$gVol. 13, no. 1, p. 7$$n1$$p7$$tGenome medicine$$v13$$x1756-994X$$y2021
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