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Dynamic changes in human single-cell transcriptional signatures during fatal sepsis.
Qiu, Xinru; Li, Jiang; Bonenfant, Jeff; Jaroszewski, Lukasz; Mittal, Aarti; Klein, Walter; Godzik, Adam; Nair, Meera G.
  • Qiu X; Graduate Program in Genetics, Genomics and Bioinformatics, University of California Riverside, Riverside, California, USA.
  • Li J; Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, USA.
  • Bonenfant J; Division of Pulmonary and Critical Care, Riverside University Health System Medical Center, Riverside, California, USA.
  • Jaroszewski L; Department of Internal Medicine, Division of Pulmonary and Critical Care, Loma Linda University, Loma Linda, California, USA.
  • Mittal A; Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, USA.
  • Klein W; Division of Pulmonary and Critical Care, Riverside University Health System Medical Center, Riverside, California, USA.
  • Godzik A; Division of Pulmonary and Critical Care, Riverside University Health System Medical Center, Riverside, California, USA.
  • Nair MG; Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, USA.
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.
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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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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