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Hidden SARS-CoV-2 Variants, Spread Found With Wastewater-Based Surveillance

NEW YORK – New research demonstrates the possibility of picking up previously undetected SARS-CoV-2 variants with wastewater sample sequencing on a college campus.

"Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission," co-senior and corresponding author Rob Knight, a pediatrics, computer science and engineering, and bioengineering researcher affiliated with the University of California at San Diego, and his colleagues wrote in Nature on Thursday.

"Unlike qPCR-based mutant surveillance, genomic surveillance using full-length virus genomes can detect which strains of SARS-CoV-2 are circulating in the population and can identify potential transmission links between infected individuals," the authors explained. "While targeted qPCR mutant panels have the ability to detect specific lineages in wastewater, they only target a small set of mutations that must be known beforehand and require development and validation time before implementation."

With a sequencing strategy that relied on enhanced viral concentration methods and deconvolution software, authors of the new study considered more than 19,900 wastewater samples collected with the help of a geographic information system at sites across the UCSD campus over 295 days.

They compared the resulting SARS-CoV-2 sequences to those detected in almost 1,500 wastewater samples collected at other sites in the San Diego area and to findings from a clinical genomic surveillance effort that involved nasal swab sampling of individuals in the community from late 2020 to September 2021.

In the process, the team uncovered wastewater spikes corresponding to increased cases. The approach also led to potential SARS-CoV-2 variants of concern weeks before they showed up in the clinical genomic surveillance setting, where SARS-CoV-2 Epsilon, Alpha, and Delta variants dominated during the time frame considered.

With the wastewater-based SARS-CoV-2 sequences in hand, the group also saw signs of viral transmission events and spread that would have been missed otherwise, including viral movements missed by clinical genomic surveillance.

"Our wastewater genomic surveillance approach identified VOCs up to two weeks prior to detection through clinical genomic surveillance, even though a large proportion of clinical SARS-CoV-2 samples are sequenced in San Diego relative to other cities in the United States," the researchers reported. "In addition to providing a detailed history of community virus spread, wastewater genomic surveillance also identified multiple instances of cryptic community transmission not observed through clinical genomic surveillance."

The investigators noted that such efforts are expected to improve further as sequencing technologies, methodologies, and related analytical approaches improve in the future. They also highlighted the possibility of putting together previously unappreciated epidemiological insights by bringing together corresponding clinical genome sequence and surveillance SARS-CoV-2 sequence data generated by wastewater sequencing.

"As SARS-CoV-2 continues to evolve, the risk of new [variants of concern] remains high, and there is a growing need to identify these viruses ahead of their proliferation in the community," the authors wrote, noting that "development of technologies that are cost-effective, reduce biases, and provide leading rather than trailing indicators of infection are essential to removing 'blind spots' in our understanding of local virus dynamics."