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Observational Study
. 2021 Aug 1;49(8):e751-e760.
doi: 10.1097/CCM.0000000000005027.

Gene Expression-Based Diagnosis of Infections in Critically Ill Patients-Prospective Validation of the SepsisMetaScore in a Longitudinal Severe Trauma Cohort

Simone Thair  1 , Caspar Mewes  2   3 , José Hinz  3 , Ingo Bergmann  2 , Benedikt Büttner  2 , Stephan Sehmisch  4 , Konrad Meissner  2 , Michael Quintel  2 , Timothy E Sweeney  1   5 , Purvesh Khatri  1   5 , Ashham Mansur  2   6
Affiliations
Observational Study

Gene Expression-Based Diagnosis of Infections in Critically Ill Patients-Prospective Validation of the SepsisMetaScore in a Longitudinal Severe Trauma Cohort

Simone Thair et al. Crit Care Med. .

Abstract

Objectives: Early diagnosis of infections is pivotal in critically ill patients. Innovative gene expression-based approaches promise to deliver precise, fast, and clinically practicable diagnostic tools to bedside. This study aimed to validate the SepsisMetaScore, an 11-gene signature previously reported by our study group, in a representative longitudinal cohort of trauma patients.

Design: Prospective observational cohort study.

Setting: Surgical ICUs of the University Medical Center Goettingen, Germany.

Patients: Critically ill patients with severe traumatic injuries.

Interventions: None.

Measurements and main results: Paired box gene (PAXgene) RNA blood tubes were drawn at predefined time points over the course of disease. The performance of the SepsisMetaScore was tested using targeted polymerase chain reaction and compared with Procalcitonin using area under the receiver operating characteristics analyses. The SepsisMetaScore showed significant differences between infected and noninfected patients (n = 52). It was able to accurately discriminate infectious from noninfectious acute inflammation with an area under the receiver operating characteristics of 0.92 (95% CI, 0.85-0.99) and significantly outperformed Procalcitonin (area under the receiver operating characteristics curve = 0.53; 95% CI, 0.42-0.64) early in the course of infection (p = 0.014).

Conclusions: We demonstrated the clinical utility for diagnosis of infections with higher accuracy using the SepsisMetaScore compared with Procalcitonin in a prospective cohort of severe trauma patients. Future studies should assess whether the SepsisMetaScore may substantially improve clinical practice by accurate differentiation of infections from sterile inflammation and identification of patients at risk for sepsis. Our results support further investigation of the SepsisMetaScore for the development of tailored precision treatment of critically ill patients.

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Conflict of interest statement

Drs. Thair and Sweeney are employees of, and shareholders in, Inflammatix, Inc. Drs. Thair, Sweeney, and Khatri received funding from Inflammatix, Inc, Burlingame, CA. Inflammatix is developing the SepsisMetaScore as part of a broader test for commercial use (HostDx-Sepsis; Inflammatix). Dr. Quintel also received funding from Xenies/Fresenius, B.Braun, and Baxter. Dr. Khatri is a shareholder in and a consultant to Inflammatix; he is funded, in part, by the Bill and Melinda Gates Foundation (OPP1113682); the National Institute of Allergy and Infectious Diseases grants 1U19AI109662, U19AI057229, and 5R01AI125197; Department of Defense contracts W81XWH-18-1-0253 and W81XWH1910235; and the Ralph & Marian Falk Medical Research Trust. The remaining authors have disclosed that they do not have any potential conflicts of interest.

References

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