Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.
Adult
Aged
Aged, 80 and over
Biomarkers
Blood Circulation
COVID-19
/ immunology
Cells, Cultured
Cohort Studies
Disease Progression
Erythroid Cells
/ pathology
Female
Gene Expression Profiling
Humans
Male
Megakaryocytes
/ physiology
Middle Aged
Plasma Cells
/ physiology
Proteomics
SARS-CoV-2
/ physiology
Sequence Analysis, RNA
Severity of Illness Index
Single-Cell Analysis
COVID-19
RNA-seq
acute respiratory distress
blood
disease trajectory
immune response
infectious disease
methylation
scRNA-seq
virus
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
15 12 2020
15 12 2020
Historique:
received:
25
09
2020
revised:
15
11
2020
accepted:
19
11
2020
pubmed:
10
12
2020
medline:
29
12
2020
entrez:
9
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33296687
pii: S1074-7613(20)30504-5
doi: 10.1016/j.immuni.2020.11.017
pmc: PMC7689306
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1296-1314.e9Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK089503
Pays : United States
Investigateurs
Nicholas E Banovich
(NE)
Tushar Desai
(T)
Oliver Eickelberg
(O)
Muzlifa Haniffa
(M)
Peter Horvath
(P)
Jonathan A Kropski
(JA)
Robert Lafyatis
(R)
Joakim Lundeberg
(J)
Kerstin Meyer
(K)
Martijn C Nawijn
(MC)
Marko Nikolic
(M)
Jose Ordovas Montanes
(J)
Dana Pe'er
(D)
Purushothama Rao Tata
(PR)
Emma Rawlins
(E)
Aviv Regev
(A)
Paul Reyfman
(P)
Christos Samakovlis
(C)
Joachim Schultze
(J)
Alex Shalek
(A)
Douglas Shepherd
(D)
Jason Spence
(J)
Sarah Teichmann
(S)
Fabian Theis
(F)
Alexander Tsankov
(A)
Maarten van den Berge
(M)
Michael von Papen
(M)
Jeffrey Whitsett
(J)
Laure Emmanuelle Zaragosi
(LE)
Angel Angelov
(A)
Robert Bals
(R)
Alexander Bartholomäus
(A)
Anke Becker
(A)
Daniela Bezdan
(D)
Ezio Bonifacio
(E)
Peer Bork
(P)
Thomas Clavel
(T)
Maria Colme-Tatche
(M)
Andreas Diefenbach
(A)
Alexander Dilthey
(A)
Nicole Fischer
(N)
Konrad Förstner
(K)
Julia-Stefanie Frick
(JS)
Julien Gagneur
(J)
Alexander Goesmann
(A)
Torsten Hain
(T)
Michael Hummel
(M)
Stefan Janssen
(S)
Jörn Kalinowski
(J)
René Kallies
(R)
Birte Kehr
(B)
Andreas Keller
(A)
Sarah Kim-Hellmuth
(S)
Christoph Klein
(C)
Oliver Kohlbacher
(O)
Jan O Korbel
(JO)
Ingo Kurth
(I)
Markus Landthaler
(M)
Yang Li
(Y)
Kerstin Ludwig
(K)
Oliwia Makarewicz
(O)
Manja Marz
(M)
Alice McHardy
(A)
Christian Mertes
(C)
Markus Nöthen
(M)
Peter Nürnberg
(P)
Uwe Ohler
(U)
Stephan Ossowski
(S)
Jörg Overmann
(J)
Silke Peter
(S)
Klaus Pfeffer
(K)
Anna R Poetsch
(AR)
Alfred Pühler
(A)
Niklaus Rajewsky
(N)
Markus Ralser
(M)
Olaf Rieß
(O)
Stephan Ripke
(S)
Ulisses Nunes da Rocha
(U)
Philip Rosenstiel
(P)
Antoine-Emmanuel Saliba
(AE)
Leif Erik Sander
(LE)
Birgit Sawitzki
(B)
Philipp Schiffer
(P)
Eva-Christina Schulte
(EC)
Joachim L Schultze
(JL)
Alexander Sczyrba
(A)
Oliver Stegle
(O)
Jens Stoye
(J)
Fabian Theis
(F)
Janne Vehreschild
(J)
Jörg Vogel
(J)
Max von Kleist
(M)
Andreas Walker
(A)
Jörn Walter
(J)
Dagmar Wieczorek
(D)
John Ziebuhr
(J)
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no conflicting interests.
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