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000178091 005__ 20211215112321.0
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000178091 041__ $$aEnglish
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000178091 1001_ $$aAschenbrenner, Anna C$$b0
000178091 245__ $$aDisease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.
000178091 260__ $$aLondon$$bBioMed Central$$c2021
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000178091 520__ $$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.
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000178091 650_7 $$2Other$$aBlood transcriptomics
000178091 650_7 $$2Other$$aCOVID-19
000178091 650_7 $$2Other$$aCo-expression analysis
000178091 650_7 $$2Other$$aDrug repurposing
000178091 650_7 $$2Other$$aGranulocytes
000178091 650_7 $$2Other$$aMolecular disease phenotypes
000178091 650_7 $$2Other$$aNeutrophils
000178091 650_7 $$2Other$$aStratification
000178091 650_7 $$2Other$$aTranscriptome
000178091 650_7 $$2NLM Chemicals$$aAntiviral Agents
000178091 650_7 $$063231-63-0$$2NLM Chemicals$$aRNA
000178091 650_2 $$2MeSH$$aAntiviral Agents: therapeutic use
000178091 650_2 $$2MeSH$$aCOVID-19: drug therapy
000178091 650_2 $$2MeSH$$aCOVID-19: pathology
000178091 650_2 $$2MeSH$$aCOVID-19: virology
000178091 650_2 $$2MeSH$$aCase-Control Studies
000178091 650_2 $$2MeSH$$aDown-Regulation
000178091 650_2 $$2MeSH$$aDrug Repositioning
000178091 650_2 $$2MeSH$$aHumans
000178091 650_2 $$2MeSH$$aNeutrophils: cytology
000178091 650_2 $$2MeSH$$aNeutrophils: immunology
000178091 650_2 $$2MeSH$$aNeutrophils: metabolism
000178091 650_2 $$2MeSH$$aPhenotype
000178091 650_2 $$2MeSH$$aPrincipal Component Analysis
000178091 650_2 $$2MeSH$$aRNA: blood
000178091 650_2 $$2MeSH$$aRNA: chemistry
000178091 650_2 $$2MeSH$$aRNA: metabolism
000178091 650_2 $$2MeSH$$aSequence Analysis, RNA
000178091 650_2 $$2MeSH$$aSeverity of Illness Index
000178091 650_2 $$2MeSH$$aTranscriptome
000178091 650_2 $$2MeSH$$aUp-Regulation
000178091 7001_ $$aMouktaroudi, Maria$$b1
000178091 7001_ $$aKrämer, Benjamin$$b2
000178091 7001_ $$aOestreich, Marie$$b3
000178091 7001_ $$aAntonakos, Nikolaos$$b4
000178091 7001_ $$aNuesch-Germano, Melanie$$b5
000178091 7001_ $$aGkizeli, Konstantina$$b6
000178091 7001_ $$aBonaguro, Lorenzo$$b7
000178091 7001_ $$aReusch, Nico$$b8
000178091 7001_ $$aBaßler, Kevin$$b9
000178091 7001_ $$aSaridaki, Maria$$b10
000178091 7001_ $$aKnoll, Rainer$$b11
000178091 7001_ $$aPecht, Tal$$b12
000178091 7001_ $$aKapellos, Theodore S$$b13
000178091 7001_ $$aDoulou, Sarandia$$b14
000178091 7001_ $$aKröger, Charlotte$$b15
000178091 7001_ $$aHerbert, Miriam$$b16
000178091 7001_ $$aHolsten, Lisa$$b17
000178091 7001_ $$aHorne, Arik$$b18
000178091 7001_ $$aGemünd, Ioanna D$$b19
000178091 7001_ $$aRovina, Nikoletta$$b20
000178091 7001_ $$aAgrawal, Shobhit$$b21
000178091 7001_ $$aDahm, Kilian$$b22
000178091 7001_ $$avan Uelft, Martina$$b23
000178091 7001_ $$aDrews, Anna$$b24
000178091 7001_ $$aLenkeit, Lena$$b25
000178091 7001_ $$aBruse, Niklas$$b26
000178091 7001_ $$aGerretsen, Jelle$$b27
000178091 7001_ $$aGierlich, Jannik$$b28
000178091 7001_ $$aBecker, Matthias$$b29
000178091 7001_ $$aHändler, Kristian$$b30
000178091 7001_ $$aKraut, Michael$$b31
000178091 7001_ $$aTheis, Heidi$$b32
000178091 7001_ $$aMengiste, Simachew$$b33
000178091 7001_ $$aDe Domenico, Elena$$b34
000178091 7001_ $$aSchulte-Schrepping, Jonas$$b35
000178091 7001_ $$aSeep, Lea$$b36
000178091 7001_ $$aRaabe, Jan$$b37
000178091 7001_ $$aHoffmeister, Christoph$$b38
000178091 7001_ $$aToVinh, Michael$$b39
000178091 7001_ $$aKeitel, Verena$$b40
000178091 7001_ $$aRieke, Gereon$$b41
000178091 7001_ $$aTalevi, Valentina$$b42
000178091 7001_ $$aSkowasch, Dirk$$b43
000178091 7001_ $$aAziz, N Ahmad$$b44
000178091 7001_ $$aPickkers, Peter$$b45
000178091 7001_ $$avan de Veerdonk, Frank L$$b46
000178091 7001_ $$aNetea, Mihai G$$b47
000178091 7001_ $$aSchultze, Joachim L$$b48
000178091 7001_ $$aKox, Matthijs$$b49
000178091 7001_ $$aBreteler, Monique M B$$b50
000178091 7001_ $$aNattermann, Jacob$$b51
000178091 7001_ $$aKoutsoukou, Antonia$$b52
000178091 7001_ $$aGiamarellos-Bourboulis, Evangelos J$$b53
000178091 7001_ $$00000-0002-9785-4197$$aUlas, Thomas$$b54
000178091 7001_ $$aInitiative, German COVID-19 Omics$$b55$$eCollaboration Author
000178091 7001_ $$aAltmüller, Janine$$b56
000178091 7001_ $$aAngelov, Angel$$b57
000178091 7001_ $$aBals, Robert$$b58
000178091 7001_ $$aBartholomäus, Alexander$$b59
000178091 7001_ $$aBecker, Anke$$b60
000178091 7001_ $$aBitzer, Michael$$b61
000178091 7001_ $$aBonifacio, Ezio$$b62
000178091 7001_ $$aBork, Peer$$b63
000178091 7001_ $$aCasadei, Nicolas$$b64
000178091 7001_ $$aClavel, Thomas$$b65
000178091 7001_ $$aColome-Tatche, Maria$$b66
000178091 7001_ $$aDiefenbach, Andreas$$b67
000178091 7001_ $$aDilthey, Alexander$$b68
000178091 7001_ $$aFischer, Nicole$$b69
000178091 7001_ $$aFörstner, Konrad$$b70
000178091 7001_ $$aFranzenburg, Sören$$b71
000178091 7001_ $$aFrick, Julia-Stefanie$$b72
000178091 7001_ $$aGabernet, Gisela$$b73
000178091 7001_ $$aGagneur, Julien$$b74
000178091 7001_ $$aGanzenmüller, Tina$$b75
000178091 7001_ $$aGöpel, Siri$$b76
000178091 7001_ $$aGoesmann, Alexander$$b77
000178091 7001_ $$aHain, Torsten$$b78
000178091 7001_ $$aHeimbach, André$$b79
000178091 7001_ $$aHummel, Michael$$b80
000178091 7001_ $$aIftner, Angelika$$b81
000178091 7001_ $$aIftner, Thomas$$b82
000178091 7001_ $$aJanssen, Stefan$$b83
000178091 7001_ $$aKalinowski, Jörn$$b84
000178091 7001_ $$aKallies, René$$b85
000178091 7001_ $$aKehr, Birte$$b86
000178091 7001_ $$aKeller, Andreas$$b87
000178091 7001_ $$aKim-Hellmuth, Sarah$$b88
000178091 7001_ $$aKlein, Christoph$$b89
000178091 7001_ $$aKohlbacher, Oliver$$b90
000178091 7001_ $$aKöhrer, Karl$$b91
000178091 7001_ $$aKorbel, Jan$$b92
000178091 7001_ $$aKühnert, Denise$$b93
000178091 7001_ $$aKurth, Ingo$$b94
000178091 7001_ $$aLandthaler, Markus$$b95
000178091 7001_ $$aLi, Yang$$b96
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000178091 7001_ $$aPühler, Alfred$$b109
000178091 7001_ $$aRajewsky, Nikolaus$$b110
000178091 7001_ $$aRalser, Markus$$b111
000178091 7001_ $$aRieß, Olaf$$b112
000178091 7001_ $$aRipke, Stephan$$b113
000178091 7001_ $$aNunes da Rocha, Ulisses$$b114
000178091 7001_ $$aRosenstiel, Philip$$b115
000178091 7001_ $$aSaliba, Antoine-Emmanuel$$b116
000178091 7001_ $$aSander, Leif Erik$$b117
000178091 7001_ $$aSawitzki, Birgit$$b118
000178091 7001_ $$aSchiffer, Philipp$$b119
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000178091 7001_ $$aSchulte, Eva-Christina$$b121
000178091 7001_ $$aSchultze, Joachim L$$b122
000178091 7001_ $$aSczyrba, Alexander$$b123
000178091 7001_ $$aSingh, Yogesh$$b124
000178091 7001_ $$aSonnabend, Michael$$b125
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000178091 7001_ $$aWieczorek, Dagmar$$b134
000178091 7001_ $$aWinkler, Sylke$$b135
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