A97-03 Consensus Sepsis Immune Dysregulation Endotyping Scores Are Quantified by the 30-Minute Point-Of-Care Triverity™ Severity Score, Which May Be Associated With Differential Response to Steroids and Anakinra

Abstract Background We performed a large-scale evaluation of existing immune endotypes in sepsis and proposed the Human Immune Dysregulation Evaluation Framework (Hi-DEF), which uses whole blood gene expression to quantify myeloid and lymphoid immune dysregulation in critical illness (Moore et al. Nature Medicine). A major barrier to clinical implementation is the lack of a rapid test to facilitate timely therapeutic decision-making. We hypothesized that the FDA-cleared TriVerity™ Severity score (a 29-mRNA-based gene score of host-immune response with 30-minute turn around time) developed by Inflammatix, Inc. would overlap with existing sepsis endotypes and could identify immune dysregulated patients who benefit from immune modulation. Methods The TriVerity Test produces three scores (Bacterial, Viral, and Severity) to identify presence and type of infection as well as severity of sepsis. The TriVerity Severity score (model IMX-SEV-4) reports a 0-50 score with 40-50 (‘Band 5’) being the highest risk. We calculated TriVerity Severity scores from RNAseq data for 2,387 samples from 7 international cohorts in the SUBSPACE consortium and performed Pearson’s correlation between TriVerity Severity scores and myeloid and lymphoid dysregulation per the Hi-DEF framework. We assessed heterogeneity of treatment effect across high and low TriVerity scores (defined as ≥ Band 3 in non-ICU populations and Band 5 in ICU populations) across two datasets: (1) VICTAS, a randomized controlled trial of steroids, vitamin C, and thiamine in sepsis, and (2) SAVE-MORE, a clinical trial of anakinra in COVID-19. Results TriVerity Severity scores were highly correlated with myeloid and lymphoid dysregulation scores (r = 0.6 and 0.61, respectively, p 2.2e-16) and Hi-DEF subgroup (figure 1A,B). In the VICTAS trial, high TriVerity Severity scores were associated with reduction in 30-day mortality (OR = 0.26, p = 0.04) in critically ill sepsis treated with vitamin C, thiamine, and hydrocortisone (figure 1C). In SAVE-MORE, high TriVerity (Band ≥3) was associated with a reduction in 28-day mortality (OR = 0.28, p = 0.04) in non-critically ill patients with COVID-19 who received anakinra (Figure 1D). Conclusion These results suggest that the TriVerity Severity score identified similar biology as Hi-DEF for sepsis endotypes and identified important heterogeneity of treatment effect in two sepsis trials. This test can be performed in 30 minutes, which with prospective validation could facilitate predictive enrichment in future clinical trials for patients most likely to benefit from immune modulation. This abstract is funded by: K12TR004930