Leveraging the U.S. blood supply to detect emerging viral threats

Abstract Emerging infectious diseases often circulate undetected until they cause clinical illness, leaving surveillance systems reactive rather than anticipatory. The U.S. blood supply, with millions of whole-blood and plasma donations annually, offers an underutilized national resource for proactive pathogen surveillance. We propose integrating metagenomic sequencing (MGS) into existing blood collection and testing workflows to detect known and novel viruses in residual samples within days of collection. Unlike current blood screening, which targets a limited set of predefined pathogens, MGS captures a broad range of viral threats, including blood- and vector-borne agents that produce asymptomatic viremia and may be missed by syndromic surveillance. Modeling suggests that an annual investment of $5.5 million could detect a novel HIV-like pathogen before it infects 0.01% of the U.S. population. Building on established donor monitoring, testing, and privacy infrastructure, blood supply sequencing represents a deployment-ready opportunity to strengthen national and global biosecurity.