Discovery and validation of transcriptional signatures to distinguish COVID-19 and other viral infections from bacterial sepsis in adults

Novel approaches to discriminate likelihood of bacterial and viral infections are required to support antimicrobial prescribing decisions and infection control practice, and, with the advent of COVID-19 new diagnostic challenges arise. Building on an existing and actively recruiting infection bioresource, we aimed to derive and validate a blood transcriptional signature to differentiate bacterial infections from viral infections including COVID-19.   Blood RNA sequencing was performed on a discovery cohort of emergency department adult patients with confirmed bacterial or viral infection. Differentially expressed host genes were analysed to derive a discriminating signature of genes that could differentiate the groups. We  developed a simple RT-qPCR test for genes in the signature and validated the signature of a new six-month prospective cohort of patients presenting with undifferentiated fever and then on a second case-control cohort of COVID-19 and bacterial infection patients.