Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission
- Creators
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Karthikeyan, Smruthi
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Levy, Joshua I.
- De Hoff, Peter
- Humphrey, Greg
- Birmingham, Amanda
- Jepsen, Kristen
- Farmer, Sawyer
- Tubb, Helena M.
- Valles, Tommy
- Tribelhorn, Caitlin E.
- Tsai, Rebecca
- Aigner, Stefan
- Sathe, Shashank
- Moshiri, Niema
- Henson, Benjamin
- Mark, Adam M.
- Hakim, Abbas
- Baer, Nathan A.
- Barber, Tom
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Belda-Ferre, Pedro
- Chacón, Marisol
- Cheung, Willi
- Cresini, Evelyn S.
- Eisner, Emily R.
- Lastrella, Alma L.
- Lawrence, Elijah S.
- Marotz, Clarisse A.
- Ngo, Toan T.
- Ostrander, Tyler
- Plascencia, Ashley
- Salido, Rodolfo A.
- Seaver, Phoebe
- Smoot, Elizabeth W.
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McDonald, Daniel
- Neuhard, Robert M.
- Scioscia, Angela L.
- Satterlund, Alysson M.
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Simmons, Elizabeth H.
- Abelman, Dismas B.
- Brenner, David
- Bruner, Judith C.
- Buckley, Anne
- Ellison, Michael
- Gattas, Jeffrey
- Gonias, Steven L.
- Hale, Matt
- Hawkins, Faith
- Ikeda, Lydia
- Jhaveri, Hemlata
- Johnson, Ted
- Kellen, Vince
- Kremer, Brendan
- Matthews, Gary
- McLawhon, Ronald W.
- Ouillet, Pierre
- Park, Daniel
- Pradenas, Allorah
- Reed, Sharon
- Riggs, Lindsay
- Sanders, Alison
- Sollenberger, Bradley
- Song, Angela
- White, Benjamin
- Winbush, Terri
- Aceves, Christine M.
- Anderson, Catelyn
- Gangavarapu, Karthik
- Hufbauer, Emory
- Kurzban, Ezra
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Lee, Justin
- Matteson, Nathaniel L.
- Parker, Edyth
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Perkins, Sarah A.
- Ramesh, Karthik S.
- Robles-Sikisaka, Refugio
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Schwab, Madison A.
- Spencer, Emily
- Wohl, Shirlee
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Nicholson, Laura
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Mchardy, Ian H.
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Dimmock, David P.
- Hobbs, Charlotte A.
- Bakhtar, Omid
- Harding, Aaron
- Mendoza, Art
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Bolze, Alexandre
- Becker, David
- Cirulli, Elizabeth T.
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Isaksson, Magnus
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Schiabor Barrett, Kelly M.
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Washington, Nicole L.
- Malone, John D.
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Murphy Schafer, Ashleigh
- Gurfield, Nikos
- Stous, Sarah
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Fielding-Miller, Rebecca
- Garfein, Richard S.
- Gaines, Tommi
- Anderson, Cheryl
- Martin, Natasha K.
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Schooley, Robert
- Austin, Brett
- MacCannell, Duncan R.
- Kingsmore, Stephen F.
- Lee, William
- Shah, Seema
- McDonald, Eric
- Yu, Alexander T.
- Zeller, Mark
- Fisch, Kathleen M.
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Longhurst, Christopher A.
- Maysent, Patty
- Pride, David
- Khosla, Pradeep K.
- Laurent, Louise C.
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Yeo, Gene W.
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Andersen, Kristian G.
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Knight, Rob
Abstract
As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.
Additional Information
Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv. This work has been funded by CDC BAA contracts 75D30121P10258 (Helix) and 75D30120C09795 (G.W.Y., R.K., L.C.L., and K.G.A.), NIH NIAID 3U19AI135995-03S2 (K.G.A.), U19AI135995 (K.G.A.), U01AI151812 (K.G.A.), NIH NCATS UL1TR002550 (K.G.A.), the Conrad Prebys Foundation (K.G.A.), NIH 5T32AI007244-38 (J.I.L.), NIH Pioneer Grant 1DP1AT010885 (R.K), NSF RAPID 2029069 (R.K.), San Diego County Health and Human Services Agency (R.F.M), NIH S10OD026929 (K.J.). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention.Additional details
- PMCID
- PMC8996633
- Eprint ID
- 118345
- Resolver ID
- CaltechAUTHORS:20221215-540121000.6
- Centers for Disease Control and Prevention
- 75D30121P10258
- Centers for Disease Control and Prevention
- 75D30120C09795
- NIH
- 3U19AI135995-03S2
- NIH
- U19AI135995
- NIH
- U01AI151812
- NIH
- UL1TR002550
- Conrad Prebys Foundation
- NIH Predoctoral Fellowship
- 5T32AI007244
- NIH
- 1DP1AT010885
- NSF
- AGS-2029069
- San Diego County
- NIH
- S10OD026929
- Created
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2022-12-17Created from EPrint's datestamp field
- Updated
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2022-12-17Created from EPrint's last_modified field
- Caltech groups
- COVID-19