Dataset Information

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

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 biases^1-3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing^4,5. 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.

SUBMITTER: Karthikeyan S

PROVIDER: S-EPMC9433318 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Karthikeyan Smruthi S Levy Joshua I JI De Hoff Peter P Humphrey Greg G Birmingham Amanda A Jepsen Kristen K Farmer Sawyer S Tubb Helena M HM Valles Tommy T Tribelhorn Caitlin E CE Tsai Rebecca R Aigner Stefan S Sathe Shashank S Moshiri Niema N Henson Benjamin B Mark Adam M AM Hakim Abbas A Baer Nathan A NA Barber Tom T Belda-Ferre Pedro P Chacón Marisol M Cheung Willi W Cresini Evelyn S ES Eisner Emily R ER Lastrella Alma L AL Lawrence Elijah S ES Marotz Clarisse A CA Ngo Toan T TT Ostrander Tyler T Plascencia Ashley A Salido Rodolfo A RA Seaver Phoebe P Smoot Elizabeth W EW McDonald Daniel D Neuhard Robert M RM Scioscia Angela L AL Satterlund Alysson M AM Simmons Elizabeth H EH Abelman Dismas B DB Brenner David D Bruner Judith C JC Buckley Anne A Ellison Michael M Gattas Jeffrey J Gonias Steven L SL Hale Matt M Hawkins Faith F Ikeda Lydia L Jhaveri Hemlata H Johnson Ted T Kellen Vince V Kremer Brendan B Matthews Gary G McLawhon Ronald W RW Ouillet Pierre P Park Daniel D Pradenas Allorah A Reed Sharon S Riggs Lindsay L Sanders Alison A Sollenberger Bradley B Song Angela A White Benjamin B Winbush Terri T Aceves Christine M CM Anderson Catelyn C Gangavarapu Karthik K Hufbauer Emory E Kurzban Ezra E Lee Justin J Matteson Nathaniel L NL Parker Edyth E Perkins Sarah A SA Ramesh Karthik S KS Robles-Sikisaka Refugio R Schwab Madison A MA Spencer Emily E Wohl Shirlee S Nicholson Laura L McHardy Ian H IH Dimmock David P DP Hobbs Charlotte A CA Bakhtar Omid O Harding Aaron A Mendoza Art A Bolze Alexandre A Becker David D Cirulli Elizabeth T ET Isaksson Magnus M Schiabor Barrett Kelly M KM Washington Nicole L NL Malone John D JD Schafer Ashleigh Murphy AM Gurfield Nikos N Stous Sarah S Fielding-Miller Rebecca R Garfein Richard S RS Gaines Tommi T Anderson Cheryl C Martin Natasha K NK Schooley Robert R Austin Brett B MacCannell Duncan R DR Kingsmore Stephen F SF Lee William W Shah Seema S McDonald Eric E Yu Alexander T AT Zeller Mark M Fisch Kathleen M KM Longhurst Christopher C Maysent Patty P Pride David D Khosla Pradeep K PK Laurent Louise C LC Yeo Gene W GW Andersen Kristian G KG Knight Rob R

Nature 20220707 7925

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 biases<sup>1-3</sup>. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing ...[more]

PMID: 35798029

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Project description:Wastewater-based epidemiology (WBE) is an effective way of tracking the appearance and spread of SARS-COV-2 lineages through communities. Beginning in early 2021, we implemented a targeted approach to amplify and sequence the receptor binding domain (RBD) of SARS-COV-2 to characterize viral lineages present in sewersheds. Over the course of 2021, we reproducibly detected multiple SARS-COV-2 RBD lineages that have never been observed in patient samples in 9 sewersheds located in 3 states in the USA. These cryptic lineages contained between 4 to 24 amino acid substitutions in the RBD and were observed intermittently in the sewersheds in which they were found for as long as 14 months. Many of the amino acid substitutions in these lineages occurred at residues also mutated in the Omicron variant of concern (VOC), often with the same substitution. One of the sewersheds contained a lineage that appeared to be derived from the Alpha VOC, but the majority of the lineages appeared to be derived from pre-VOC SARS-COV-2 lineages. Specifically, several of the cryptic lineages from New York City appeared to be derived from a common ancestor that most likely diverged in early 2020. While the source of these cryptic lineages has not been resolved, it seems increasingly likely that they were derived from immunocompromised patients or animal reservoirs. Our findings demonstrate that SARS-COV-2 genetic diversity is greater than what is commonly observed through routine SARS-CoV-2 surveillance. Wastewater sampling may more fully capture SARS-CoV-2 genetic diversity than patient sampling and could reveal new VOCs before they emerge in the wider human population.Author summaryDuring the COVID-19 pandemic, wastewater-based epidemiology has become an effective public health tool. Because many infected individuals shed SARS-CoV-2 in feces, wastewater has been monitored to reveal infection trends in the sewersheds from which the samples were derived. Here we report novel SARS-CoV-2 lineages in wastewater samples obtained from 3 different states in the USA. These lineages appeared in specific sewersheds intermittently over periods of up to 14 months, but generally have not been detected beyond the sewersheds in which they were initially found. Many of these lineages may have diverged in early 2020. Although these lineages share considerable overlap with each other, they have never been observed in patients anywhere in the world. While the wastewater lineages have similarities with lineages observed in long-term infections of immunocompromised patients, animal reservoirs cannot be ruled out as a potential source.

Dataset Information

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

Publications

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

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