This session will cover novel technologies that leverage the host immune response to infection and will discuss how host response tests could change diagnostic and treatment workflows for patients with suspected acute infections and sepsis.

For over two decades, numerous investigative groups and industry partners have pursued the development and implementation of multi-analyte, host response-based, infectious disease diagnostics. Propelled by the recent pandemic of COVID-19 and the ongoing fight against antimicrobial resistance, regulatory agencies, payors, and end-users are gearing up for this revolution in diagnostics. Dr. Woods will review the current landscape and what the future may hold.

Clinical metagenomic next-generation sequencing (mNGS) is an emerging approach to diagnose nearly all potential infections, whether viral, bacterial, fungal, or parasitic, in a single assay. Here we will discuss validation and implementation of these mNGS assays in the clinical laboratory and their clinical impact. We will also discuss concurrent host response analyses performed on metagenomic data to aid in the differential diagnosis of infections.

Immunocompromised patients, including cancer patients, are at increased risk for infections. Several methods are currently available for diagnosis of infectious diseases, each with advantages and limitations. Microbial metagenomics has been evaluated for its potential to provide a more comprehensive, pathogen-agnostic approach to infectious disease diagnostics. In this talk, the utility of microbial metagenomics in an immunocompromised cancer patient population will be examined and opportunity for further optimization discussed.

To address critical areas of diagnostic needs borne out from experiences with COVID-19 diagnostic and surveillance testing, NIH launched the Rapid Acceleration of Diagnostics Radical (RADx-rad) program. Presentation covers ongoing RADx-rad efforts from two specific initiatives that showcase non-traditional ways to identify disease biomarkers: 1) Exosome-based technologies for multi-parametric detection of SARS-CoV-2, and 2) Breath-based platforms for the detection of volatile organic compound (VOC) signatures unique to COVID-19.

Sepsis, a leading cause of death worldwide, involves a dysregulated host response to infection. Existing clinical sepsis diagnostics, however, either detect only microbes or host biomarkers of infection. This presentation will describe a new method for accurate sepsis diagnosis based on integrating host gene expression profiling and metagenomic pathogen detection from plasma nucleic acid.

Infections associated with the respiratory tract account for more than 40% of the antibiotics prescribed. Unfortunately, a substantial portion of these antibiotics may not be warranted. One of the factors driving overuse of antibiotics in this setting is failure to identify the pathogen responsible for the infection. Advances in CLIA-waived and home-use diagnostics can help establish a causative pathogen and decrease unnecessary antibiotic use.

Optimizing outpatient antibiotic use in the outpatient setting often means managing patient expectations. Some inappropriate antibiotic prescribing is a result of it being easier to prescribe an antibiotic for a patient than explain why it may be unnecessary. The patient expectation of an antibiotic may be related to the time and cost necessary to be seen in most healthcare settings. Point-of-care testing in pharmacies or at home has the potential to improve outpatient antibiotic use by lowering the costs and adherence to prescribing guidelines. This session will discuss how diagnostic testing in pharmacy and home settings has been shown to improve outpatient antibiotic use.