Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19.
Cell
; 184(7): 1836-1857.e22, 2021 04 01.
Article
in English
| MEDLINE | ID: covidwho-1077815
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Severity of Illness Index
/
Dendritic Cells
/
Killer Cells, Natural
/
Gene Expression
/
Cytokines
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
/
Young adult
Language:
English
Journal:
Cell
Year:
2021
Document Type:
Article
Affiliation country:
J.cell.2021.02.018
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