W113 - Identification of Conserved Detrimental Host Immune Response Predicts Severity of Bacterial and Viral Infections

Background: Host immune response has been repeatedly shown to diagnose the presence and type of infection. Recently, we described a 42-gene blood-based signature, conserved across viruses, that correlates with and predicts the severity of viral infection, irrespective of age, sex, and host or pathogen genetics. This 42-gene signature is composed of 4 modules (2 protective, 2 detrimental). We hypothesize that these modules are also associated with disease severity in patients with bacterial infection.

Methods: We analyzed 58 publicly available datasets of blood transcriptome profiles from 4989 patients (2300 healthy, 1169 with bacterial infection, 1520 with viral infection), and co-normalized them using COCONUT. Severity was stratified into seven categories ranging from healthy to fatal. We evaluated our four module and composite severe-or-mild “SoM” scores, and applied our previously described 7-gene signature (7GS, distinguishing viral from bacterial infection) to both bacterial and viral samples.

Results: Two detrimental module scores were positively correlated with severity of bacterial infections (module 1: r=0.64, module 2: r=0.53), and one of two protective modules was inversely correlated (module 4: r=-0.59). Module 3, protective in viral infections, was minimally positively correlated with severity of bacterial illness (module 3: r=0.20). SoM score distinguished non-severe bacterial infections from severe bacterial infection (r=0.63, AUROC=0.77, 95% CI:0.73-0.80).

Conclusion: SoM score can distinguish patients with severe infection, irrespective of bacterial or viral etiology. When used with our 7GS, it may help decide whether a patient warrants (1) treatment with an antibiotic or (2) discharge or admission upon presentation to an emergency department.