Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission

Smruthi Karthikeyan, Joshua I. Levy, Peter Hoff, Greg Humphrey, Amanda Birmingham, Kristen Jepsen, Sawyer Farmer, Helena M. Tubb, Tommy Valles, Caitlin E. Tribelhorn, Rebecca Tsai, Stefan Aigner, Shashank Sathe, Niema Moshiri, Benjamin Henson, Adam M. Mark, Abbas Hakim, Nathan A. Baer, Tom Barber, Pedro Belda-Ferre, Marisol Chacón, Willi Cheung, Evelyn S. Cresini, Emily R. Eisner, Alma L. Lastrella, Elijah S. Lawrence, Clarisse A. Marotz, Toan T. Ngo, Tyler Ostrander, Ashley Plascencia, Rodolfo A. Salido, Phoebe Seaver, Elizabeth W. Smoot, Daniel McDonald, Robert M. Neuhard, Angela L. Scioscia, Alysson M. Satterlund, Elizabeth H. Simmons, Dismas B. Abelman, David Brenner, Judith C. Bruner, Anne Buckley, Michael Ellison, Jeffrey Gattas, Steven L. Gonias, Matt Hale, Faith Hawkins, Lydia Ikeda, Hemlata Jhaveri, Ted Johnson, Vince Kellen, Brendan Kremer, Gary Matthews, Ronald W. McLawhon, Pierre Ouillet, Daniel Park, Allorah Pradenas, Sharon Reed, Lindsay Riggs, Alison Sanders, Bradley Sollenberger, Angela Song, Benjamin White, Terri Winbush, Christine M. Aceves, Catelyn Anderson, Karthik Gangavarapu, Emory Hufbauer, Ezra Kurzban, Justin Lee, Nathaniel L. Matteson, Edyth Parker, Sarah A. Perkins, Karthik S. Ramesh, Refugio Robles-Sikisaka, Madison A. Schwab, Emily Spencer, Shirlee Wohl, Laura Nicholson, Ian H. McHardy, David P. Dimmock, Charlotte A. Hobbs, Omid Bakhtar, Aaron Harding, Art Mendoza, Alexandre Bolze, David Becker, Elizabeth T. Cirulli, Magnus Isaksson, Kelly M. Schiabor Barrett, Nicole L. Washington, John D. Malone, Ashleigh Murphy Schafer, Nikos Gurfield, Sarah Stous, Rebecca Fielding-Miller, Richard S. Garfein, Tommi Gaines, Cheryl Anderson, Natasha K. Martin, Robert Schooley, Brett Austin, Duncan R. MacCannell, Stephen F. Kingsmore, William Lee, Seema Shah, Eric McDonald, Alexander T. Yu, Mark Zeller, Kathleen M. Fisch, Christopher Longhurst, Patty Maysent, David Pride, Pradeep K. Khosla, Louise C. Laurent, Gene W. Yeo, Kristian G. Andersen and Rob Knight ()
Additional contact information
Smruthi Karthikeyan: University of California San Diego
Joshua I. Levy: The Scripps Research Institute
Peter Hoff: University of California San Diego
Greg Humphrey: University of California San Diego
Amanda Birmingham: University of California San Diego
Kristen Jepsen: University of California San Diego
Sawyer Farmer: University of California San Diego
Helena M. Tubb: University of California San Diego
Tommy Valles: University of California San Diego
Caitlin E. Tribelhorn: University of California San Diego
Rebecca Tsai: University of California San Diego
Stefan Aigner: University of California San Diego
Shashank Sathe: University of California San Diego
Niema Moshiri: University of California San Diego
Benjamin Henson: University of California San Diego
Adam M. Mark: University of California San Diego
Abbas Hakim: University of California San Diego
Nathan A. Baer: University of California San Diego
Tom Barber: University of California San Diego
Pedro Belda-Ferre: University of California San Diego
Marisol Chacón: University of California San Diego
Willi Cheung: University of California San Diego
Evelyn S. Cresini: University of California San Diego
Emily R. Eisner: University of California San Diego
Alma L. Lastrella: University of California San Diego
Elijah S. Lawrence: University of California San Diego
Clarisse A. Marotz: University of California San Diego
Toan T. Ngo: University of California San Diego
Tyler Ostrander: University of California San Diego
Ashley Plascencia: University of California San Diego
Rodolfo A. Salido: University of California San Diego
Phoebe Seaver: University of California San Diego
Elizabeth W. Smoot: University of California San Diego
Daniel McDonald: University of California San Diego
Robert M. Neuhard: University of California San Diego
Angela L. Scioscia: University of California San Diego
Alysson M. Satterlund: University of California San Diego
Elizabeth H. Simmons: University of California San Diego
Dismas B. Abelman: University of California San Diego
David Brenner: University of California San Diego
Judith C. Bruner: University of California San Diego
Anne Buckley: University of California San Diego
Michael Ellison: University of California San Diego
Jeffrey Gattas: University of California San Diego
Steven L. Gonias: University of California San Diego
Matt Hale: University of California San Diego
Faith Hawkins: University of California San Diego
Lydia Ikeda: University of California San Diego
Hemlata Jhaveri: University of California San Diego
Ted Johnson: University of California San Diego
Vince Kellen: University of California San Diego
Brendan Kremer: University of California San Diego
Gary Matthews: University of California San Diego
Ronald W. McLawhon: University of California San Diego
Pierre Ouillet: University of California San Diego
Daniel Park: University of California San Diego
Allorah Pradenas: University of California San Diego
Sharon Reed: University of California San Diego
Lindsay Riggs: University of California San Diego
Alison Sanders: University of California San Diego
Bradley Sollenberger: University of California San Diego
Angela Song: University of California San Diego
Benjamin White: University of California San Diego
Terri Winbush: University of California San Diego
Christine M. Aceves: The Scripps Research Institute
Catelyn Anderson: The Scripps Research Institute
Karthik Gangavarapu: The Scripps Research Institute
Emory Hufbauer: The Scripps Research Institute
Ezra Kurzban: The Scripps Research Institute
Justin Lee: The Scripps Research Institute
Nathaniel L. Matteson: The Scripps Research Institute
Edyth Parker: The Scripps Research Institute
Sarah A. Perkins: The Scripps Research Institute
Karthik S. Ramesh: The Scripps Research Institute
Refugio Robles-Sikisaka: The Scripps Research Institute
Madison A. Schwab: The Scripps Research Institute
Emily Spencer: The Scripps Research Institute
Shirlee Wohl: The Scripps Research Institute
Laura Nicholson: Scripps Health, San Diego
Ian H. McHardy: Scripps Health, San Diego
David P. Dimmock: Rady Children’s Institute for Genomic Medicine
Charlotte A. Hobbs: Rady Children’s Institute for Genomic Medicine
Omid Bakhtar: Sharp Healthcare
Aaron Harding: Sharp Healthcare
Art Mendoza: Sharp Healthcare
Alexandre Bolze: Helix
David Becker: Helix
Elizabeth T. Cirulli: Helix
Magnus Isaksson: Helix
Kelly M. Schiabor Barrett: Helix
Nicole L. Washington: Helix
John D. Malone: County of San Diego Health and Human Services Agency
Ashleigh Murphy Schafer: County of San Diego Health and Human Services Agency
Nikos Gurfield: County of San Diego Health and Human Services Agency
Sarah Stous: County of San Diego Health and Human Services Agency
Rebecca Fielding-Miller: University of California San Diego
Richard S. Garfein: University of California San Diego
Tommi Gaines: University of California San Diego
Cheryl Anderson: University of California San Diego
Natasha K. Martin: University of California San Diego
Robert Schooley: University of California San Diego
Brett Austin: Sharp Healthcare
Duncan R. MacCannell: Office of Advanced Molecular Detection, Centers for Disease Control and Prevention
Stephen F. Kingsmore: Rady Children’s Institute for Genomic Medicine
William Lee: Helix
Seema Shah: County of San Diego Health and Human Services Agency
Eric McDonald: County of San Diego Health and Human Services Agency
Alexander T. Yu: COVID-19 Detection, Investigation, Surveillance, Clinical, and Outbreak Response, California Department of Public Health
Mark Zeller: The Scripps Research Institute
Kathleen M. Fisch: University of California San Diego
Christopher Longhurst: University of California San Diego
Patty Maysent: University of California San Diego
David Pride: University of California San Diego
Pradeep K. Khosla: University of California San Diego
Louise C. Laurent: University of California San Diego
Gene W. Yeo: University of California San Diego
Kristian G. Andersen: The Scripps Research Institute
Rob Knight: University of California San Diego

Nature, 2022, vol. 609, issue 7925, 101-108

Abstract: 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 and/or sequencing capacity, which can also introduce biases1–3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. 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 developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified 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.

Date: 2022
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Citations: View citations in EconPapers (6)

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DOI: 10.1038/s41586-022-05049-6

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