Dynamic changes in human single-cell transcriptional signatures during fatal sepsis.
J Leukoc Biol
; 110(6): 1253-1268, 2021 12.
Article
in English
| MEDLINE | ID: covidwho-1437055
ABSTRACT
Systemic infections, especially in patients with chronic diseases, may result in sepsis an explosive, uncoordinated immune response that can lead to multisystem organ failure with a high mortality rate. Patients with similar clinical phenotypes or sepsis biomarker expression upon diagnosis may have different outcomes, suggesting that the dynamics of sepsis is critical in disease progression. A within-subject study of patients with Gram-negative bacterial sepsis with surviving and fatal outcomes was designed and single-cell transcriptomic analyses of peripheral blood mononuclear cells (PBMC) collected during the critical period between sepsis diagnosis and 6 h were performed. The single-cell observations in the study are consistent with trends from public datasets but also identify dynamic effects in individual cell subsets that change within hours. It is shown that platelet and erythroid precursor responses are drivers of fatal sepsis, with transcriptional signatures that are shared with severe COVID-19 disease. It is also shown that hypoxic stress is a driving factor in immune and metabolic dysfunction of monocytes and erythroid precursors. Last, the data support CD52 as a prognostic biomarker and therapeutic target for sepsis as its expression dynamically increases in lymphocytes and correlates with improved sepsis outcomes. In conclusion, this study describes the first single-cell study that analyzed short-term temporal changes in the immune cell populations and their characteristics in surviving or fatal sepsis. Tracking temporal expression changes in specific cell types could lead to more accurate predictions of sepsis outcomes and identify molecular biomarkers and pathways that could be therapeutically controlled to improve the sepsis trajectory toward better outcomes.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Gram-Negative Bacterial Infections
/
Sepsis
/
Transcriptome
/
COVID-19
/
Leukocytes
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
J Leukoc Biol
Year:
2021
Document Type:
Article
Affiliation country:
JLB.5MA0721-825R
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