Harnessing the host response for precision infectious disease diagnosis

SUMMARY Detection of the presence of infection and its etiology must be accurate and timely to facilitate appropriate antimicrobial use. Diagnostic strategies that rely solely on pathogen detection often are insufficient due to poor test characteristics, inability to differentiate colonization from infection, or protracted delay to result. Understanding the human response across different pathogens on a clinical and molecular level can provide more accurate, timely, and useful answers, especially in critical illness and diagnostic uncertainty. Improvements in understanding the human immune response including genomics, protein analysis, gene expression, and cellular morphology have led to rapid innovation of new host response-based diagnostic tests. This review describes the limitations of pathogen-focused technology and the benefits of examining the breadth of immune response to diagnose infection. It then explores biomarkers that have been studied for this purpose and scrutinizes the performance of host-based multianalyte testing. Currently cleared diagnostics and those in late-stage development are described in depth, with a focus on the purpose of testing and its utility for clinicians. Finally, it concludes by examining opportunities for further host response-derived diagnostic innovation.