VB10, a new blood biomarker for differential diagnosis and recovery monitoring of acute viral and bacterial infections.

ABSTRACT

BACKGROUND: Precise differential diagnosis between acute viral and bacterial infections is important to enable appropriate therapy, avoid unnecessary antibiotic prescriptions and optimize the use of hospital resources. A systems view of host response to infections provides opportunities for discovering sensitive and robust molecular diagnostics. METHODS: We combine blood transcriptomes from six independent datasets (n = 756) with a knowledge-based human protein-protein interaction network, identifies subnetworks capturing host response to each infection class, and derives common response cores separately for viral and bacterial infections. We subject the subnetworks to a series of computational filters to identify a parsimonious gene panel and a standalone diagnostic score that can be applied to individual samples. We rigorously validate the panel and the diagnostic score in a wide range of publicly available datasets and in a newly developed Bangalore-Viral Bacterial (BL-VB) cohort. FINDING: We discover a 10-gene blood-based biomarker panel (Panel-VB) that demonstrates high predictive performance to distinguish viral from bacterial infections, with a weighted mean AUROC of 0.97 (95% CI 0.96-0.99) in eleven independent datasets (n = 898). We devise a new stand-alone patient-wise score (VB10) based on the panel, which shows high diagnostic accuracy with a weighted mean AUROC of 0.94 (95% CI 0.91-0.98) in 2996 patient samples from 56 public datasets from 19 different countries. Further, we evaluate VB10 in a newly generated South Indian (BL-VB, n = 56) cohort and find 97% accuracy in the confirmed cases of viral and bacterial infections. We find that VB10 is (a) capable of accurately identifying the infection class in culture-negative indeterminate cases, (b) reflects recovery status, and (c) is applicable across different age groups, covering a wide spectrum of acute bacterial and viral infections, including uncharacterized pathogens. We tested our VB10 score on publicly available COVID-19 data and find that our score detected viral infection in patient samples. INTERPRETATION: Our results point to the promise of VB10 as a diagnostic test for precise diagnosis of acute infections and monitoring recovery status. We expect that it will provide clinical decision support for antibiotic prescriptions and thereby aid in antibiotic stewardship efforts. FUNDING: Grand Challenges India, Biotechnology Industry Research Assistance Council (BIRAC), Department of Biotechnology, Govt. of India.