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Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19
Immunity (Cambridge, Mass.), 2020-12, Vol.53 (6), p.1296-1314.e9
2020

Details

Autor(en) / Beteiligte
Titel
Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19
Ist Teil von
  • Immunity (Cambridge, Mass.), 2020-12, Vol.53 (6), p.1296-1314.e9
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2020
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • 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. [Display omitted] •SARS-CoV2 infection elicits dynamic changes of circulating cells in the blood•Severe COVID-19 is characterized by increased metabolically active plasmablasts•Elevation of IFN-activated megakaryocytes and erythroid cells in severe COVID-19•Cell-type-specific expression signatures are associated with a fatal COVID-19 outcome Bernardes et al. explore COVID-19 disease trajectories by performing longitudinal multi-omics analyses in peripheral blood samples from hospitalized patients. The analyses identify increased numbers of plasmablasts, interferon-activated megakaryocytes, and erythroid cells as hallmarks of severe disease and define molecular signatures linked to a fatal COVID-19 disease outcome.
Sprache
Englisch
Identifikatoren
ISSN: 1074-7613
eISSN: 1097-4180
DOI: 10.1016/j.immuni.2020.11.017
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7689306
Format
–
Schlagworte
acute respiratory distress, Adult, Aged, Aged, 80 and over, Biomarkers, blood, Blood Circulation, Cells, Cultured, Cohort Studies, Coronaviruses, COVID-19, COVID-19 - immunology, COVID-19 - metabolism, Cytokines, Datasets, Deoxyribonucleic acid, Disease Progression, disease trajectory, DNA, DNA methylation, Erythroid cells, Erythroid Cells - pathology, Erythropoiesis, Female, Flow cytometry, Gene expression, Gene Expression Profiling, Genomics, Hospitalization, Humans, Hypoxia, Immune response, Immune system, infectious disease, Interferon, Male, Megakaryocytes, Megakaryocytes - physiology, methylation, Middle Aged, Neutrophils, Patients, Peripheral blood, Plasma Cells - physiology, Principal components analysis, Proteomics, RNA-seq, SARS-CoV-2 - physiology, scRNA-seq, Sequence Analysis, RNA, Severe acute respiratory syndrome coronavirus 2, Severity of Illness Index, Single-Cell Analysis, Temporal resolution, Transcription factors, Tumor necrosis factor-TNF, Viral diseases, virus

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