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Covid Sepsis Gene Expression Subphenotypes Manifest Differential Plasma Protein Signatures
Critical Care Medicine ; 51(1 Supplement):594, 2023.
Article in English | EMBASE | ID: covidwho-2190679
ABSTRACT

INTRODUCTION:

Transcriptome-derived sepsis subphenotypes, termed 'adaptive', 'inflammopathic' and 'coagulopathic', have been reliably identified in sepsis cohorts, however plasma proteomics in these groups have not been well characterized. We hypothesized that inflammatory and vascular injury markers would be elevated in the inflammopathic and coagulopathic groups compared to the adaptive group. METHOD(S) We prospectively enrolled and obtained blood from 130 inpatients with COVID19-related sepsis. Severity was classified by NIH ordinal scale. Gene expression analysis was performed by Nanostring nCounter (Inflammatix). Inflammatory proteins interleukin (IL)-6, IL8, IL10, IL1RA, IL1RL1, and IFNg and vascular markers ANGPT2, sICAM, vWF, ADAMTS13, and protein C were measured with OLINK proximity extension assay. Clinical variables were compared by chi-square and protein levels were compared using ANOVA with Bonferroni adjustment. RESULT(S) The transcriptomic classifier identified 32% (41) inflammopathic, 50% (65) adaptive and 18% (24) coagulopathic subjects. The inflammopathic group had more patients requiring mechanical ventilation (39% vs 9% vs 21%;p < 0.001) and higher 90-day mortality (32% vs 8% vs 13%, p = 0.016). Inflammatory cytokines IL8 and IL10 were significantly higher in inflammopathic compared to adaptive (p=0.038 and p=0.017 respectively), but not compared to coagulopathic (p>0.99 and p=0.24, respectively). Both the inflammopathic and coagulopathic groups expressed higher IL1RL1 and interferon-gamma compared to adaptive (IL1RL1;p< 0.001, p=0.002, IFNg;p=0.007, p=0.001). Plasma IL6 and IL1RA did not differ between groups, nor did many vascular proteins. The inflammopathic group expressed higher sICAM (p=0.049 vs adaptive) and lower ADAMTS13 compared to the adaptive group, and the coagulopathic group did not differ in its vascular protein expression. CONCLUSION(S) Transcriptomic subphenotypes are present in COVID-19 sepsis at similar proportions to non-COVID-19 sepsis. Inflammopathic subjects manifested higher severity of illness at admission, higher expression of inflammatory proteins and higher mortality. Markers of vascular injury did not distinguish the coagulopathic group. Integrating RNA and protein expression may offer new insights to host immune dysregulation during COVID sepsis.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Critical Care Medicine Year: 2023 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Critical Care Medicine Year: 2023 Document Type: Article