Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients
Author:
Aschenbrenner Anna C.ORCID, Mouktaroudi MariaORCID, Krämer BenjaminORCID, Antonakos NikolaosORCID, Oestreich MarieORCID, Gkizeli KonstantinaORCID, Nuesch-Germano MelanieORCID, Saridaki MariaORCID, Bonaguro LorenzoORCID, Reusch NicoORCID, Baßler KevinORCID, Doulou SarandiaORCID, Knoll RainerORCID, Pecht TalORCID, Kapellos Theodore S.ORCID, Rovina NikolettaORCID, Kröger CharlotteORCID, Herbert MiriamORCID, Holsten LisaORCID, Horne ArikORCID, Gemünd Ioanna D.ORCID, Agrawal Shobhit, Dahm KilianORCID, Uelft Martina van, Drews AnnaORCID, Lenkeit LenaORCID, Bruse NiklasORCID, Gerretsen JelleORCID, Gierlich Jannik, Becker MatthiasORCID, Händler Kristian, Kraut Michael, Theis Heidi, Mengiste Simachew, Domenico Elena DeORCID, Schulte-Schrepping JonasORCID, Seep Lea, Raabe JanORCID, Hoffmeister Christoph, ToVinh Michael, Keitel Verena, Rieke GereonORCID, Talevi ValentinaORCID, Aziz N. AhmadORCID, Pickkers PeterORCID, van de Veerdonk Frank, Netea Mihai G.ORCID, Schultze Joachim L.ORCID, Kox MatthijsORCID, Breteler Monique M.B.ORCID, Nattermann JacobORCID, Koutsoukou AntoniaORCID, Giamarellos-Bourboulis Evangelos J.ORCID, Ulas ThomasORCID,
Abstract
SUMMARYThe 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 calls for a better characterization and understanding of the changes in the immune system. 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 11 COVID-19 patients. Comparison of COVID-19 blood transcriptomes with those of a collection of over 2,800 samples derived from 11 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
13 articles.
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