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We developed a novel indexing method, Melvin\u2019s Index, that provides a normalized and standardized metric of wastewater pathogen load for qPCR assays that is resilient to surveillance site variation. To demonstrate the utility of Melvin\u2019s Index, we used qRT-PCR to measure SARS-CoV-2 genomic RNA levels in influent wastewater from 19 municipal wastewater treatment facilities (WWTF\u2019s) of varying sizes and served populations across the state of Minnesota during the Summer of 2020. SARS-CoV-2 RNA was detected at each WWTF during the 20-week sampling period at a mean concentration of 8.5\u2009\u00d7\u200910<jats:sup>4<\/jats:sup> genome copies\/L (range 3.2\u2009\u00d7\u200910<jats:sup>2<\/jats:sup>\u20131.2\u2009\u00d7\u200910<jats:sup>9<\/jats:sup> genome copies\/L). Lag analysis of trends in Melvin\u2019s Index values and clinical COVID-19 cases showed that increases in indexed wastewater SARS-CoV-2 levels precede new clinical cases by 15\u201317\u00a0days at the statewide level and by up to 25\u00a0days at the regional\/county level. Melvin\u2019s Index is a reliable WBE method and can be applied to both WWTFs that serve a wide range of population sizes and to large regions that are served by multiple WWTFs.<\/jats:p>","DOI":"10.1038\/s41598-021-00853-y","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T11:04:13Z","timestamp":1635764653000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["A novel wastewater-based epidemiology indexing method predicts SARS-CoV-2 disease prevalence across treatment facilities in metropolitan and regional populations"],"prefix":"10.1038","volume":"11","author":[{"given":"Richard G.","family":"Melvin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily N.","family":"Hendrickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabiha","family":"Chaudhry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onimitein","family":"Georgewill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Freese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Schacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Glenn E.","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"853_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S095026881000316X","volume":"140","author":"T Hovi","year":"2012","unstructured":"Hovi, T. et al. 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