Abstract

Early detection of novel pathogens can prevent or substantially mitigate biological incidents, including pandemics. Metagenomic next-generation sequencing (mNGS) of symptomatic clinical samples may enable detection early enough to contain outbreaks, limit international spread, and expedite countermeasure development. In this article, we propose a clinical mNGS architecture we call "Threat Net," which focuses on the hospital emergency department as a high-yield surveillance location. We develop a susceptible-exposed-infected-removed (SEIR) simulation model to estimate the effectiveness of Threat Net in detecting novel respiratory pathogen outbreaks. Our analysis serves to quantify the value of routine clinical mNGS for respiratory pandemic detection by estimating the cost and epidemiological effectiveness at differing degrees of hospital coverage across the United States. We estimate that a biological threat detection network such as Threat Net could be deployed across hospitals covering 30% of the population in the United States. Threat Net would cost between $400 million and $800 million annually and have a 95% chance of detecting a novel respiratory pathogen with traits of SARS-CoV-2 after 10 emergency department presentations and 79 infections across the United States. Our analyses suggest that implementing Threat Net could help prevent or substantially mitigate the spread of a respiratory pandemic pathogen in the United States.

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