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

Abstract Emerging infectious diseases often circulate undetected until they cause clinical illness, creating serious risks for public health and biosecurity. The U.S. blood supply, with millions of routinely collected and quality-controlled donations, offers an untapped national resource for proactive pathogen surveillance. We propose integrating metagenomic sequencing (MGS) into existing blood and plasma collection workflows to detect novel or unexpected viruses in deidentified residual samples. This approach complements environmental sampling from wastewater and air by enabling detection of blood-borne and vector-borne pathogens that cause asymptomatic viremia, threats that may be poorly captured by other systems. Our modeling analysis suggests that this system is highly cost-effective: an estimated annual investment of approximately $5.8 million could detect a novel HIV-like pathogen before it infects 0.01% of the population. Building on existing blood donor testing infrastructure, privacy frameworks, and an analogous national serosurveillance network established during COVID-19, MGS blood monitoring represents a deployment-ready, cost-effective addition to national biosecurity infrastructure, transforming the blood supply from a safety measure into an early warning system for emerging viral threats.