학술논문

Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission
Document Type
article
Author
Karthikeyan, SmruthiLevy, Joshua IDe Hoff, PeterHumphrey, GregBirmingham, AmandaJepsen, KristenFarmer, SawyerTubb, Helena MValles, TommyTribelhorn, Caitlin ETsai, RebeccaAigner, StefanSathe, ShashankMoshiri, NiemaHenson, BenjaminMark, Adam MHakim, AbbasBaer, Nathan ABarber, TomBelda-Ferre, PedroChacón, MarisolCheung, WilliCresini, Evelyn SEisner, Emily RLastrella, Alma LLawrence, Elijah SMarotz, Clarisse ANgo, Toan TOstrander, TylerPlascencia, AshleySalido, Rodolfo ASeaver, PhoebeSmoot, Elizabeth WMcDonald, DanielNeuhard, Robert MScioscia, Angela LSatterlund, Alysson MSimmons, Elizabeth HAbelman, Dismas BBrenner, DavidBruner, Judith CBuckley, AnneEllison, MichaelGattas, JeffreyGonias, Steven LHale, MattHawkins, FaithIkeda, LydiaJhaveri, HemlataJohnson, TedKellen, VinceKremer, BrendanMatthews, GaryMcLawhon, Ronald WOuillet, PierrePark, DanielPradenas, AllorahReed, SharonRiggs, LindsaySanders, AlisonSollenberger, BradleySong, AngelaWhite, BenjaminWinbush, TerriAceves, Christine MAnderson, CatelynGangavarapu, KarthikHufbauer, EmoryKurzban, EzraLee, JustinMatteson, Nathaniel LParker, EdythPerkins, Sarah ARamesh, Karthik SRobles-Sikisaka, RefugioSchwab, Madison ASpencer, EmilyWohl, ShirleeNicholson, LauraMcHardy, Ian HDimmock, David PHobbs, Charlotte ABakhtar, OmidHarding, AaronMendoza, ArtBolze, AlexandreBecker, DavidCirulli, Elizabeth TIsaksson, MagnusSchiabor Barrett, Kelly MWashington, Nicole LMalone, John DSchafer, Ashleigh MurphyGurfield, NikosStous, SarahFielding-Miller, RebeccaGarfein, Richard SGaines, TommiAnderson, CherylMartin, Natasha K
Source
Nature. 609(7925)
Subject
Biodefense
Human Genome
Lung
Emerging Infectious Diseases
Vaccine Related
Biotechnology
Genetics
Prevention
Infection
Good Health and Well Being
COVID-19
Humans
RNA
Viral
SARS-CoV-2
Sequence Analysis
RNA
Wastewater
Wastewater-Based Epidemiological Monitoring
General Science & Technology
Language
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.