A-384 Laboratory Evaluation of the SeptiCyte Rapid Host Response Assay In Differentiating Infection-Positive Versus Infection-Negative Systemic Inflammation Patients Suspected of Sepsis
Authors: Sankari L , Dolin H , Hejal R , Mohammad H , Windau A , Greig C , Savadekar D , Weisenberger C , Remy K , Jacono F , Zhang X S 
Published: September 2023

Abstract

Background
Early diagnosis of sepsis is critical for timely treatment but remains challenging. A rapid host response assay, SeptiCyte, was recently approved by the FDA for aiding early differentiation of infection-positive from infection-negative systemic inflammation in patients suspected of sepsis. This test is a fully automated reverse transcription polymerase chain reaction (RT-qPCR) assay that quantifies changes in the expression of two host immune response genes and results are available in about 1 hour. The present study aimed to evaluate the SeptiCyte assay performance in a clinical setting at a large medical center.

Methods
Eighty-two patients admitted to the University Hospitals Cleveland Medical Center with suspected sepsis from July to September 2022 were included in the study. SeptiCyte samples were obtained at the time of initial evaluation. In addition, healthy donor blood samples and extracted RNA samples were also utilized for assay validation. The SeptiCyte assay was performed according to the manufacturer's instructions using multi-chambered fluidic cartridges and the Idylla Console (Immunexpress, Seattle, WA). The assay result was reported as the SeptiScore (range 0–15), a calculated ratio of the expression of two host immune response genes, and the SeptiCyte band (ranging from 1 to 4, with 1 indicating the lowest risk of sepsis and 4 indicating the highest risk). The assay cutoff values are 5.0, 6.2 and 7.4 respectively for the band 2, 3 and 4.

Results
Intra- and inter-assay precision was 0.2–6.2% and 0–3.2%, respectively. % Recovery at the cutoff for band 3 (SeptiScore 6.0) was 102.4% with a CV of 2.4%. Method comparison with the Immunexpress lab demonstrated equivalent performance, as evidenced by a slope of 0.99 and an intercept of 0.27 by Deming regression. SeptiScore showed a weak positive correlation with CRP (Correlation Coefficient 0.389, P &lt; 0.01) but no association with procalcitonin (n = 76), lactate (n = 78), international normalized ratio (INR), platelet, neutrophil, lymphocyte, or white blood cell (WBC) count (n = 82). CRP (n = 71) median concentration in patients with band 4 (16.8) was significantly higher than in patients who were band 1 (3.6). The SeptiScore of blood culture positive cases (n = 22) was 7.2 ± 2.0 (mean ± SD) and that of pathogen negative non-sepsis (by sepsis retrospective review of event only, n = 10) cases was 5.6 ± 1.6 (P &lt; 0.05). In addition, the median SeptiScore was notably higher in patients with viral infection compared to those without infection (9.2 vs 6.2, P &lt; 0.05). Further analysis showed 92% (11/12) of patients with hematologic cancer were categorized as band 4 including one non-sepsis case per the retrospective review. SeptiScore was similar between patients with non-hematologic cancer and those without malignancy (P &gt; 0.05).

Conclusion
The SeptiCyte RAPID assay showed good analytical performance. SeptiScore represents an independent factor to quantify host response in patients suspected of sepsis. It may add value in aiding differentiation between infection-positive from infection-negative systemic inflammation with promising results in patients with viral infections or those with positive blood cultures. The negative predictive value of low SeptiScore within band 1 or 2 may need further investigation.