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Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission
Smruthi Karthikeyan; Joshua I Levy; Peter De 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; Abbas Hakim; Nathan A Baer; Tom Barber; Pedro Belda-Ferre; Marisol Chacon; Willi Cheung; Evelyn S Crescini; 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 Carbone Bruner; Anne Buckley; Michael Ellison; Jeffrey Gattas; Steven L Gonias; Matt Hale; Faith Kirkham Hawkins; Lydia Ikeda; Hemlata Jhaveri; Ted Johnson; Vince Kellen; Brendan Kremer; Gary C. Matthews; Ronald McLawhon; Pierre Ouillet; Daniel Park; Allorah Pradenas; Sharon Reed; Lindsay Riggs; Alison M. 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; Tommi Gaines; Richard Garfein; Cheryl A. M. Anderson; Natasha K. Martin; Robert T Schooley; Brett Austin; Duncan R. MacCannell; Stephen F Kingsmore; William Lee; Seema Shah; Eric McDonald; Alexander T. Yu; Mark Zeller; Kathleen M Fisch; Christopher A. Longhurst; Patty Maysent; David Pride; Pradeep K. Khosla; Louise C Laurent; Gene W Yeo; Kristian G Andersen; Rob Knight.
Affiliation
  • Smruthi Karthikeyan; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Joshua I Levy; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Peter De Hoff; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Greg Humphrey; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Amanda Birmingham; Center for Computational Biology and Bioinformatics, University of California San Diego, La Jolla, CA, USA
  • Kristen Jepsen; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA
  • Sawyer Farmer; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Helena M. Tubb; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Tommy Valles; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Caitlin E Tribelhorn; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Rebecca Tsai; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Stefan Aigner; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Shashank Sathe; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Niema Moshiri; Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
  • Benjamin Henson; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA
  • Abbas Hakim; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Nathan A Baer; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Tom Barber; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Pedro Belda-Ferre; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Marisol Chacon; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Willi Cheung; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Evelyn S Crescini; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Emily R Eisner; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Alma L Lastrella; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Elijah S Lawrence; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Clarisse A Marotz; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Toan T Ngo; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Tyler Ostrander; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Ashley Plascencia; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Rodolfo A Salido; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Phoebe Seaver; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Elizabeth W Smoot; Expedited COVID Identification Environment (EXCITE) Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Daniel McDonald; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Robert M Neuhard; Operational Strategic Initiatives, University of California San Diego, La Jolla, CA, USA
  • Angela L Scioscia; Student Health and Well-Being, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, CA, USA
  • Alysson M. Satterlund; Student Affairs, University of California San Diego, La Jolla, CA, USA
  • Elizabeth H Simmons; Academic Affairs, University of California San Diego, La Jolla, CA, USA
  • Dismas B. Abelman; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • David Brenner; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Judith Carbone Bruner; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Anne Buckley; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Michael Ellison; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Jeffrey Gattas; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Steven L Gonias; Department of Pathology, University of California San Diego, La Jolla, CA, USA
  • Matt Hale; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Faith Kirkham Hawkins; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Lydia Ikeda; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Hemlata Jhaveri; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Ted Johnson; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Vince Kellen; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Brendan Kremer; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Gary C. Matthews; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Ronald McLawhon; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Pierre Ouillet; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Daniel Park; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Allorah Pradenas; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Sharon Reed; Department of Pathology and Medicine, University of California San Diego, La Jolla, CA, USA
  • Lindsay Riggs; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Alison M. Sanders; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Bradley Sollenberger; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Angela Song; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Benjamin White; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Terri Winbush; Return to Learn, University of California San Diego, La Jolla, CA, USA
  • Christine M Aceves; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Catelyn Anderson; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Karthik Gangavarapu; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Emory Hufbauer; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Ezra Kurzban; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Justin Lee; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Nathaniel L Matteson; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Edyth Parker; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Sarah A Perkins; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Karthik S Ramesh; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Refugio Robles-Sikisaka; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Madison A Schwab; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Emily Spencer; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Shirlee Wohl; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Laura Nicholson; Scripps Health
  • Ian H Mchardy; Scripps Health
  • David P Dimmock; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA
  • Charlotte A Hobbs; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA
  • Omid Bakhtar; Sharp Healthcare, San Diego, CA, USA
  • Aaron Harding; Sharp Healthcare, San Diego, CA, USA
  • Art Mendoza; Sharp Healthcare, San Diego, CA, USA
  • Alexandre Bolze; Helix, San Mateo, CA, USA
  • David Becker; Helix, San Mateo, CA, USA
  • Elizabeth T Cirulli; Helix, San Mateo, CA, USA
  • Magnus Isaksson; Helix, San Mateo, CA, USA
  • Kelly M Schiabor Barrett; Helix, San Mateo, CA, USA
  • Nicole L Washington; Helix, San Mateo, CA, USA
  • John D Malone; County of San Diego Health and Human Services Agency, San Diego, CA, USA
  • Ashleigh Murphy Schafer; County of San Diego Health and Human Services Agency, San Diego, CA, USA
  • Nikos Gurfield; County of San Diego Health and Human Services Agency, San Diego, CA, USA
  • Sarah Stous; County of San Diego Health and Human Services Agency, San Diego, CA, USA
  • Rebecca Fielding-Miller; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA; Division of Infectious Disease and Globa
  • Tommi Gaines; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA
  • Richard Garfein; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA
  • Cheryl A. M. Anderson; Herbert Wertheim School of Public Health and Human Longevity Science , Division of Hypertension and Nephrology, University of California San Diego, La Jolla, CA
  • Natasha K. Martin; Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, USA
  • Robert T Schooley; Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, USA
  • Brett Austin; County of San Diego Health and Human Services Agency, San Diego, CA, USA
  • Duncan R. MacCannell; Office of Advanced Molecular Detection, Centers for Disease Control and Prevention, Atlanta, GA, USA
  • Stephen F Kingsmore; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA
  • William Lee; Helix, San Mateo, CA, USA
  • Seema Shah; County of San Diego Health and Human Services Agency, San Diego, CA, USA
  • Eric McDonald; County of San Diego Health and Human Services Agency, San Diego, CA, USA
  • Alexander T. Yu; COVID-19 Detection, Investigation, Surveillance, Clinical, and Outbreak Response, California Department of Public Health, Richmond, CA, USA
  • Mark Zeller; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
  • Kathleen M Fisch; Center for Computational Biology and Bioinformatics, Department of Obstetrics, Gynecology, and Reproductive Science
  • Christopher A. Longhurst; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA; Department of Biomedical Informatics, University of California, San Diego, La J
  • Patty Maysent; Office of the UC San Diego Health CEO, University of California, San Diego
  • David Pride; Departments of Pathology and Medicine, University of California, San Diego, La Jolla, CA
  • Pradeep K. Khosla; Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
  • Louise C Laurent; Sanford Consortium of Regenerative Medicine, University of California San Diego, La Jolla, CA, Department of Obstetrics, Gynecology, and Reproductive Sciences,
  • Gene W Yeo; Sanford Consortium of Regenerative Medicine, University of California San Diego, La Jolla, CA, Department of Cellular and Molecular Medicine, University of Cali
  • Kristian G Andersen; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA, Scripps Research Translational Institute, La Jolla, CA, USA
  • Rob Knight; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA,
Preprint in English | medRxiv | ID: ppmedrxiv-21268143
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.
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Full text: Available Collection: Preprints Database: medRxiv Type of study: Experimental_studies / Observational study / Prognostic study Language: English Year: 2021 Document type: Preprint
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Full text: Available Collection: Preprints Database: medRxiv Type of study: Experimental_studies / Observational study / Prognostic study Language: English Year: 2021 Document type: Preprint