Your browser doesn't support javascript.
Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.
Aschenbrenner, Anna C; Mouktaroudi, Maria; Krämer, Benjamin; Oestreich, Marie; Antonakos, Nikolaos; Nuesch-Germano, Melanie; Gkizeli, Konstantina; Bonaguro, Lorenzo; Reusch, Nico; Baßler, Kevin; Saridaki, Maria; Knoll, Rainer; Pecht, Tal; Kapellos, Theodore S; Doulou, Sarandia; Kröger, Charlotte; Herbert, Miriam; Holsten, Lisa; Horne, Arik; Gemünd, Ioanna D; Rovina, Nikoletta; Agrawal, Shobhit; Dahm, Kilian; van Uelft, Martina; Drews, Anna; Lenkeit, Lena; Bruse, Niklas; Gerretsen, Jelle; Gierlich, Jannik; Becker, Matthias; Händler, Kristian; Kraut, Michael; Theis, Heidi; Mengiste, Simachew; De Domenico, Elena; Schulte-Schrepping, Jonas; Seep, Lea; Raabe, Jan; Hoffmeister, Christoph; ToVinh, Michael; Keitel, Verena; Rieke, Gereon; Talevi, Valentina; Skowasch, Dirk; Aziz, N Ahmad; Pickkers, Peter; van de Veerdonk, Frank L; Netea, Mihai G; Schultze, Joachim L; Kox, Matthijs.
  • Aschenbrenner AC; Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Mouktaroudi M; PRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
  • Krämer B; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Oestreich M; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
  • Antonakos N; 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
  • Nuesch-Germano M; Department I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
  • Gkizeli K; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Bonaguro L; 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
  • Reusch N; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Baßler K; 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
  • Saridaki M; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Knoll R; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Pecht T; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Kapellos TS; 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
  • Doulou S; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Kröger C; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Herbert M; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Holsten L; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Horne A; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Gemünd ID; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Rovina N; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Agrawal S; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Dahm K; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • van Uelft M; 1st Department of Pulmonary Medicine and Intensive Care Unit, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
  • Drews A; West German Genome Center (WGGC), University of Bonn, Bonn, Germany.
  • Lenkeit L; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Bruse N; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Gerretsen J; PRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
  • Gierlich J; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Becker M; Department of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
  • Händler K; Department of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
  • Kraut M; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Theis H; PRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
  • Mengiste S; PRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
  • De Domenico E; PRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
  • Schulte-Schrepping J; PRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
  • Seep L; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Raabe J; PRECISE Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
  • Hoffmeister C; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • ToVinh M; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Keitel V; Department I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
  • Rieke G; Department I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
  • Talevi V; Department I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
  • Skowasch D; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • Aziz NA; Department I of Internal Medicine, University Hospital of Bonn (UKB), Bonn, Germany.
  • Pickkers P; Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • van de Veerdonk FL; Department of Internal Medicine II, Section of Pneumology, University Hospital of Bonn (UKB), Bonn, Germany.
  • Netea MG; Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Schultze JL; Department of Neurology, Faculty of Medicine, University of Bonn, Bonn, Germany.
  • Kox M; Department of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Genome Med ; 13(1): 7, 2021 01 13.
Article in English | MEDLINE | ID: covidwho-1027902
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Transcriptome / COVID-19 / Neutrophils Type of study: Observational study / Prognostic study / Randomized controlled trials / Risk factors Limits: Humans Language: English Journal: Genome Med Year: 2021 Document Type: Article Affiliation country: S13073-020-00823-5

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Transcriptome / COVID-19 / Neutrophils Type of study: Observational study / Prognostic study / Randomized controlled trials / Risk factors Limits: Humans Language: English Journal: Genome Med Year: 2021 Document Type: Article Affiliation country: S13073-020-00823-5