Sequencing for Sepsis

Early sepsis diagnosis has the potential to save millions of lives. The life-threatening condition is estimated to contribute to nearly 20 percent of all global deaths each year – highlighting the massive need for a faster, more accurate prospective diagnostic process.

With no specific pathogen identified in over 30 percent of sepsis cases, treatment can be tricky. Some drugs, especially broad-spectrum antibiotics, see frequent overuse due to an abundance of caution and the need for rapid intervention. But this overuse can spur resistance, meaning that those drugs will have less power down the road. In light of this, fast and accurate sepsis diagnosis can not only save lives, but also mitigate the growing threat of antimicrobial resistance. To that end, researchers are now investigating the use of transcriptional profiling to help identify pathogens and select appropriate treatments for patients with sepsis.

A recent study used RNA sequencing on blood specimens to see the transcriptional differences between adult intensive care patients with clinically confirmed sepsis and those with no evidence of infection. There were also differences between sepsis originating in the bloodstream and sepsis originating in nearby tissue. Analysis revealed that patients with sepsis exhibit upregulation of genes related to neutrophil degranulation and innate immune signaling alongside concomitant downregulation of pathways related to translation and ribosomal RNA processing.

Next, to better define a comprehensive classification for sepsis diagnosis, the researchers examined the whole-blood gene expression of patients with confirmed sepsis (both blood and non-bloodstream varieties). This allowed them to identify genes that were most distinguishable between patients with and without sepsis. The findings indicate that sepsis has a unique host transcriptional signature characterized by expression of interferon and other signaling pathways. The team also found biologically relevant host transcripts in plasma, which could see clinical application in light of the increased use of plasma metagenomic next-generation sequencing (mNGS) in hospitals.

Pathogen detection alone was not always enough to secure a sepsis diagnosis; sensitivity varies by organism for both culture-based and plasma mNGS methods. Combining pathogen detection with a patient’s transcriptional profile, however, showed promise as a tool to rule sepsis in or out and to help identify the right treatment for each patient – fast.