Loading...
Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.
Bernardes, Joana P Mishra, Neha Tran, Florian Bahmer, Thomas Best, Lena Blase, Johanna I Bordoni, Dora Franzenburg, Jeanette Geisen, Ulf Josephs-Spaulding, Jonathan
Bernardes, Joana P
Mishra, Neha
Tran, Florian
Bahmer, Thomas
Best, Lena
Blase, Johanna I
Bordoni, Dora
Franzenburg, Jeanette
Geisen, Ulf
Josephs-Spaulding, Jonathan
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2020-11-26
Submitted date
Files
Other Titles
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.
Citation
mmunity. 2020 Dec 15;53(6):1296-1314.e9. doi: 10.1016/j.immuni.2020.11.017. Epub 2020 Nov 26.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
1097-4180
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International