Evidence map›Paper›PMID 33296687›Full record

ArticleImmunity2020

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

Joana P Bernardes, Neha Mishra, Florian Tran, Thomas Bahmer, Lena Best, Johanna I Blase, Dora Bordoni, Jeanette Franzenburg, Ulf Geisen, Jonathan Josephs-Spaulding and 62 more

Open access · bronzeAbstract read
In one paragraph

Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
253citing papers in PubMed, 4 pooled it
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

253 citing papers in PubMed, 4 syntheses or guidelines pooled it, 404 citations in OpenAlex.

  1. Pooled it
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  4. Resolving SARS-CoV-2 CD4Cell reports. Medicine · 2022
    Pooled it
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  19. Longitudinal omics data analysis: approaches and applications.Computational and structural biotechnology journal · 2026
    Review
  20. Article

193 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

72 authors at 12 institutions in 3 countries.

Joana P BernardesInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Neha MishraInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Florian TranInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Thomas BahmerDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Lena BestInstitute for Experimental Medicine, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Johanna I BlaseInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Dora BordoniInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Jeanette FranzenburgInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany; Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein, 24105 Kiel and 23562 Lübeck, Germany.
Ulf GeisenSection for Rheumatology, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Jonathan Josephs-SpauldingInstitute for Experimental Medicine, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Philipp KöhlerDepartment I of Internal Medicine, University of Cologne and University Hospital Cologne; German Center for Infection Research, Partner Site Bonn-Cologne and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 50937 Cologne, Germany.
Axel KünstnerCenter for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Germany.
Elisa RosatiInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Anna C AschenbrennerGenomics & Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany; Departments of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; 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.
Petra BacherInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany; Institute of Immunology, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Nathan BaranInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Teide BoysenInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Burkhard BrandtInstitute of Clinical Chemistry, University Medical Center Schleswig-Holstein, 24105 Kiel and 23562 Lübeck, Germany.
Niklas BruseDepartments of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Jonathan DörrSection for Rheumatology, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Andreas DrägerDepartment of Computer Science, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen and German Center for Infection Research (DZIF), Partner site Tübingen, 72076 Tübingen, Germany.
Gunnar ElkeDepartment of Anaesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
David EllinghausInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Julia FischerDepartment I of Internal Medicine, University of Cologne and University Hospital Cologne; German Center for Infection Research, Partner Site Bonn-Cologne and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Germany.
Michael ForsterInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Sören FranzenburgInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Norbert FreyDepartment of Internal Medicine III, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Anette FriedrichsDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Janina FußInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Andreas GlückDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Jacob HammInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Finn HinrichsenInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Marc P HoeppnerInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Simon ImmInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Ralf JunkerInstitute of Clinical Chemistry, University Medical Center Schleswig-Holstein, 24105 Kiel and 23562 Lübeck, Germany.
Sina KaiserSection for Rheumatology, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Ying H KanInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Rainer KnollSystems 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.
Christoph LangeDivision of Clinical Infectious Diseases, Research Center Borstel and German Center for Infection Research (DZIF), TTU-TB, 23845 Borstel, Germany.
Georg LaueInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Clemens LierInstitute of Clinical Chemistry, University Medical Center Schleswig-Holstein, 24105 Kiel and 23562 Lübeck, Germany.
Matthias LindnerDepartment of Anaesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Georgios MarinosInstitute for Experimental Medicine, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Robert MarkewitzInstitute of Clinical Chemistry, University Medical Center Schleswig-Holstein, 24105 Kiel and 23562 Lübeck, Germany.
Jacob NattermannDepartment of Internal Medicine I and German Center for Infection Research (DZIF), University of Bonn, 53217 Bonn, Germany.
Rainer NothDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Peter PickkersDepartments of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Klaus F RabeDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany;  LungenClinic Grosshansdorf, Airway Research Centre North, German Centre for Lung Research, 22927 Grosshansdorf, Germany.
Alina RenzDepartment of Computer Science, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen and German Center for Infection Research (DZIF), Partner site Tübingen, 72076 Tübingen, Germany.
Christoph RöckenDepartment of Pathology, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Jan RuppDepartment of Infectious Diseases and Microbiology, University of Lübeck, 23562 Lübeck, Germany.
Annika SchaffarzykSection for Rheumatology, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Alexander ScheffoldInstitute of Immunology, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Jonas Schulte-SchreppingGenomics & Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany; Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany.
Domagoj SchunkDepartment for Emergency Medicine, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Dirk SkowaschSection of Pneumology, Department of Internal Medicine II, University Hospital Bonn, , 53127 Bonn, Germany.
Thomas UlasGenomics & 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.
Klaus-Peter WandingerInstitute of Clinical Chemistry, University Medical Center Schleswig-Holstein, 24105 Kiel and 23562 Lübeck, Germany.
Michael WittigInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Johannes ZimmermannInstitute for Experimental Medicine, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Hauke BuschLübeck Institute of Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany.
Bimba F HoyerSection for Rheumatology, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Christoph KaletaInstitute for Experimental Medicine, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Jan HeyckendorfDepartment of Internal Medicine III, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Matthijs KoxGenomics & Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
Jan RybnikerDepartment I of Internal Medicine, University of Cologne and University Hospital Cologne; German Center for Infection Research, Partner Site Bonn-Cologne and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Germany.
Stefan SchreiberInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Joachim L SchultzeGenomics & 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.
Philip RosenstielInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany. Electronic address: p.rosenstiel@mucosa.de.
HCA Lung Biological Network
Deutsche COVID-19 Omics Initiative (DeCOI)
Christian-Albrechts-Universität zu Kiel · DEUniversity Hospital Schleswig-Holstein · DEUniversity of Bonn · DEBirkbeck, University of London · GBUniversity of Cologne · DEGerman Center for Infection Research · DEGerman Center for Neurodegenerative Diseases · DERadboud University Nijmegen · NLUniversity of Lübeck · DEClinical Research Center Kiel · DEGerman Center for Lung Research · DEUniversity Hospital Bonn · DE

Funding

Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joyce Lee · 2010 to 2026
$20.3M
NIDDK NIH HHS P30 DK089503
6 · The paper itself

Abstract

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, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We 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. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.

Indexed as

AdultAgedAged, 80 and overBiomarkersBlood CirculationCells, CulturedCohort StudiesCOVID-19Disease ProgressionErythroid CellsFemaleGene Expression ProfilingHumansMaleMegakaryocytesMiddle AgedBiomarkersacute respiratory distressbloodCOVID-19disease trajectoryimmune responseinfectious diseasemethylationRNA-seqscRNA-seqvirus

Identifiers

PMID33296687
PMCPMC7689306
OpenAlexW3108714922

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.