Time-resolved Systems Immunology Reveals a Late Juncture Linked to Fatal COVID-19
Can Liu, Andrew J. Martins, William W. Lau, Nicholas Rachmaninoff, Jinguo Chen, Luisa Imberti, Darius Mostaghimi, Danielle L. Fink, Peter D. Burbelo, Kerry Dobbs, Ottavia M. Delmonte, Neha Bansal, Laura Failla, Alessandra Sottini, Eugenia Quiros-Roldan, Kyu Lee Han, Brian A. Sellers, Foo Cheung, Rachel Sparks, Tae-Wook Chun, Susan Moir, Michail S. Lionakis, NIAID COVID Consortium, COVID Clinicians, Camillo Rossi, Helen C. Su, Douglas B. Kuhns, Jeffrey I. Cohen, Luigi D. Notarangelo, John S. Tsang
Abstract
COVID-19 exhibits extensive patient-to-patient heterogeneity. To link immune response variation to disease severity and outcome over time, we longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T cell receptor sequence simultaneously in single peripheral immune cells from COVID-19 patients. Conditional-independence network analysis revealed primary correlates of disease severity, including gene expression signatures of apoptosis in plasmacytoid dendritic cells and attenuated inflammation but increased fatty acid metabolism in CD56dimCD16hi NK cells linked positively to circulating interleukin (IL)-15. CD8+ T cell activation was apparent without signs of exhaustion. Although cellular inflammation was depressed in severe patients early after hospitalization, it became elevated by days 17–23 post symptom onset, suggestive of a late wave of inflammatory responses. Furthermore, circulating protein trajectories at this time were divergent between and predictive of recovery versus fatal outcomes. Our findings stress the importance of timing in the analysis, clinical monitoring, and therapeutic intervention of COVID-19.
Datasets
1. Time-resolved Systems Immunology Reveals a Late Juncture Linked to Fatal COVID-19: Adaptive Cells
Metadata
tissue_ontology_term_id
author_cell_type
disease_ontology_term_id
days_since_hospitalized
donor_id
severity
ever_admitted_to_icu
days_since_onset
timepoint
dsm_severity_score_group
outcome
material_type
development_stage_ontology_term_id
cell_type_ontology_term_id
self_reported_ethnicity_ontology_term_id
assay_ontology_term_id
sex_ontology_term_id
organism_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
UBERON:0000178246964 cells CD4-positive, alpha-beta memory T cell94519 cells CD8-positive, alpha-beta memory T cell42346 cells naive CD4+ T cell31734 cells naive CD8+ T cell13910 cells mucosal invariant T cell (MAIT)6305 cells gamma-delta T cell5693 cells double negative T cell (DNT)5164 cells regulatory T cell3041 cells double-positive T cell (DPT)174 cells MONDO:0100096178805 cells HsapDv:000014827474 cells HsapDv:000014724897 cells HsapDv:000016719051 cells HsapDv:000014916663 cells HsapDv:000013916066 cells HsapDv:000015215826 cells HsapDv:000017313004 cells HsapDv:000014611854 cells HsapDv:000021010570 cells HANCESTRO:0005150976 cells NCBITaxon:9606246964 cells CD4-positive, alpha-beta memory T cell94519 cells CD8-positive, alpha-beta memory T cell42346 cells naive thymus-derived CD4-positive, alpha-beta T cell31734 cells naive thymus-derived CD8-positive, alpha-beta T cell13910 cells mucosal invariant T cell6305 cells gamma-delta T cell5693 cells double negative thymocyte5164 cells regulatory T cell3041 cells double-positive, alpha-beta thymocyte174 cells 54-year-old human stage27474 cells 53-year-old human stage24897 cells 73-year-old human stage19051 cells 55-year-old human stage16663 cells 45-year-old human stage16066 cells 58-year-old human stage15826 cells 79-year-old human stage13004 cells 52-year-old human stage11854 cells 84-year-old human stage10570 cells 77-year-old human stage9646 cells 50-year-old human stage9420 cells 59-year-old human stage9121 cells 30-year-old human stage7724 cells 51-year-old human stage7444 cells 63-year-old human stage6869 cells 24-year-old human stage6807 cells 74-year-old human stage6674 cells 66-year-old human stage6329 cells 61-year-old human stage5241 cells 49-year-old human stage5078 cells 37-year-old human stage1740 cells 60-year-old human stage1276 cells 47-year-old human stage1086 cells 40-year-old human stage1046 cells 57-year-old human stage1000 cells 32-year-old human stage974 cells 67-year-old human stage958 cells 70-year-old human stage955 cells 71-year-old human stage884 cells 35-year-old human stage870 cells 78-year-old human stage229 cells 76-year-old human stage188 cells 2. Time-resolved Systems Immunology Reveals a Late Juncture Linked to Fatal COVID-19: Innate Cells
Metadata
dsm_severity_score_group
disease_ontology_term_id
severity
tissue_ontology_term_id
timepoint
outcome
days_since_hospitalized
donor_id
days_since_onset
author_cell_type
ever_admitted_to_icu
material_type
development_stage_ontology_term_id
cell_type_ontology_term_id
self_reported_ethnicity_ontology_term_id
assay_ontology_term_id
sex_ontology_term_id
organism_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
UBERON:0000178125117 cells classical monocyte78908 cells non-classical monocyte6160 cells NK_CD56loCD16lo3825 cells NK_CD56hiCD16lo1237 cells conventional dendritic cell991 cells plasmacytoid dendritic cell787 cells intermediate monocyte358 cells HsapDv:000014811624 cells HsapDv:000014711095 cells HsapDv:000014910881 cells HANCESTRO:000586864 cells NCBITaxon:9606125117 cells classical monocyte78908 cells CD16-positive, CD56-dim natural killer cell, human28705 cells non-classical monocyte6160 cells natural killer cell3825 cells CD16-negative, CD56-bright natural killer cell, human1237 cells conventional dendritic cell991 cells plasmacytoid dendritic cell787 cells intermediate monocyte358 cells 54-year-old human stage11624 cells 53-year-old human stage11095 cells 55-year-old human stage10881 cells 58-year-old human stage9456 cells 73-year-old human stage9051 cells 79-year-old human stage8313 cells 45-year-old human stage6924 cells 59-year-old human stage6292 cells 52-year-old human stage5104 cells 77-year-old human stage4684 cells 50-year-old human stage4227 cells 63-year-old human stage3006 cells 84-year-old human stage2988 cells 37-year-old human stage2856 cells 66-year-old human stage2676 cells 30-year-old human stage2573 cells 49-year-old human stage2510 cells 74-year-old human stage2220 cells 78-year-old human stage2208 cells 51-year-old human stage1728 cells 70-year-old human stage1685 cells 61-year-old human stage1660 cells 67-year-old human stage1635 cells 76-year-old human stage1572 cells 71-year-old human stage1547 cells 60-year-old human stage1209 cells 24-year-old human stage1062 cells 57-year-old human stage908 cells 40-year-old human stage903 cells 47-year-old human stage875 cells 35-year-old human stage860 cells 32-year-old human stage785 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/ed9185e3-5b82-40c7-9824-b2141590c7f0
Alias names
GSE161918, PMID33713619, PMC7874909
Cite this study
Liu, C., Martins, A.J., Lau, W.W., Rachmaninoff, N., Chen, J., Imberti, L., Mostaghimi, D., Fink, D.L., Burbelo, P.D., Dobbs, K. and Delmonte, O.M., 2021. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19. Cell, 184(7), pp.1836-1857. https://doi.org/10.1016/j.cell.2021.02.018
