A New Era in Host Response Biomarkers to Guide Precision Medicine for Infectious Diseases

The World Health Organization estimates that 10 million lives and 100 trillion USD in economic output yearly will be at risk by 2050 due to antimicrobial resistance [1]. This looming crisis is exacerbated by excessive and inappropriate antibiotic use, driven in part by inadequate diagnostic information. Clinical syndromes, such as pharyngitis, otitis media, and acute respiratory illness, present particular diagnostic challenges since viral and bacterial etiologies present similarly. Additionally, clinicians may struggle to rule out bacterial-viral co-infection when a viral pathogen is identified or have difficulty distinguishing colonization from infection. For example, up to 25% of adolescents and young adults are asymptomatic carriers of pharyngeal Streptococcus pyogenes, making a positive rapid strep test difficult to interpret [2]. Attempts to discriminate bacterial from viral infection have historically utilized a variety of single-analyte biomarkers, such as white blood cell (WBC) count, blood neutrophilia, C-reactive protein (CRP), and procalcitonin (PCT), although their value can be limited by poor sensitivity and specificity [3]. The global COVID-19 pandemic has only magnified the problem, rendering traditional single-analyte biomarkers difficult to interpret in the setting of a pronounced inflammatory response that can mimic the stereotypical bacterial response [4].