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Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

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Updated August 30, 2022

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, the authors performed a longitudinal multi-omics study using a two-center cohort of 14 patients. They analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients.

Philip RosenstielInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holsteinp.rosenstiel@mucosa.de
Joana P Bernardes1
Neha Mishra1
Florian Tran1
Thomas Bahmer2
Lena Best3
Johanna I Blase1
Dora Bordoni1
Jeanette Franzenburg1
Ulf Geisen4
Jonathan Josephs-Spaulding3
Philipp Köhler5
Axel Künstner6
Elisa Rosati1
Anna C Aschenbrenner7
Petra Bacher1
Nathan Baran1
Teide Boysen1
Burkhard Brandt8
Niklas Bruse9
Jonathan Dörr4
Andreas Dräger10
Gunnar Elke11
David Ellinghaus1
Julia Fischer5
Michael Forster1
Andre Franke1
Sören Franzenburg1
Norbert Frey12
Anette Friedrichs2
Janina Fuß1
Andreas Glück2
Jacob Hamm1
Finn Hinrichsen1
Marc P Hoeppner1
Simon Imm1
Ralf Junker8
Sina Kaiser4
Ying H Kan1
Rainer Knoll13
Christoph Lange14
Georg Laue1
Clemens Lier8
Matthias Lindner11
Georgios Marinos3
Robert Markewitz8
Jacob Nattermann15
Rainer Noth16
Peter Pickkers17
Klaus F Rabe2
Alina Renz10
Christoph Röcken18
Jan Rupp19
Annika Schaffarzyk4
Alexander Scheffold20
Jonas Schulte-Schrepping7
Domagoj Schunk21
Dirk Skowasch22
Thomas Ulas23
Klaus-Peter Wandinger24
Michael Wittig1
Johannes Zimmermann25
Hauke Busch26
Bimba F Hoyer27
Christoph Kaleta25
Jan Heyckendorf28
Matthijs Kox7
Jan Rybniker5
Stefan Schreiber1
Joachim L Schultze7
Philip Rosenstiel1
1Institute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein
2Department of Internal Medicine I, University Medical Center Schleswig-Holstein
3Institute for Experimental Medicine, Kiel University and University Medical Center Schleswig-Holstein
4Section for Rheumatology, Department of Internal Medicine I, University Medical Center Schleswig-Holstein
5Department I of Internal Medicine, University of Cologne and University Hospital Cologne
6Center for Molecular Medicine Cologne (CMMC), University of Cologne
7Genomics & Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn
8Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein
9Departments of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center
10Department of Computer Science, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen
11Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein
12Department of Internal Medicine III, University Medical Center Schleswig-Holstein
13Systems Medicine, German Center for Neurodegenerative Diseases (DZNE)
14Division of Clinical Infectious Diseases, Research Center Borstel and German Center for Infection Research (DZIF)
15Department of Internal Medicine I and German Center for Infection Research (DZIF), University of Bonn, 53217 Bonn, Germany.
16Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
17Departments of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
18Department of Pathology, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
19Department of Infectious Diseases and Microbiology, University of Lübeck
20Institute of Immunology, University Medical Center Schleswig-Holstein
21Department for Emergency Medicine, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
22Section of Pneumology, Department of Internal Medicine II, University Hospital Bonn, , 53127 Bonn, Germany.
23Genomics & Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany; Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, 53127 Bonn, Germany.
24Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein, 24105 Kiel and 23562 Lübeck, Germany.
25Institute for Experimental Medicine, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
26Lübeck Institute of Experimental Dermatology, University of Lübeck
27Section for Rheumatology, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
28Department of Internal Medicine III, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Ami Day

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/ec6476ee-2949-41f3-947b-8eef41d6d3ac

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://beta.fastgenomics.org/p/565003
INSDC Project Accessions:GEO Series Accessions:INSDC Study Accessions:

Atlas

None

Analysis Portals

None

Project Label

LongitudinalMultiomicsCovid19

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

blood

Organ Part

Unspecified

Selected Cell Types

Unspecified

Disease Status (Specimen)

23 disease statuses

Disease Status (Donor)

23 disease statuses

Development Stage

human adult stage

Library Construction Method

3 library construction methods

Nucleic Acid Source

2 nucleic acid sources

Paired End

false, true

Analysis Protocol

analysis _protocol_bulk_BCR, analysis _protocol_bulk_RNA, cell_type_analysis_protocol, gene_expression_quantification_protocol

File Format

5 file formats

Cell Count Estimate

358.9k

Donor Count

28
csv3 file(s)fastq.gz290 file(s)h5ad4 file(s)txt.gz147 file(s)xlsx1 file(s)