Two years into the COVID-19 pandemic, trends point to a transition for the SARS-CoV-2 virus into an endemic agent. As major surveillance infrastructure scales back, it will be critical to maintain a cost-effective, simple, and rapid strategy for detecting and monitoring the spread of new variants. The key to such a strategy? Wastewater, where many disease agents leave their unique signature.

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On November 26, 2021, the World Health Organization warned of a highly transmissible new SARS-CoV-2 variant of concern: Omicron. Countries worldwide, including the United States, responded quickly with new travel restrictions designed to delay its spread. It was the latest twist in the two-year-old saga of COVID-19.

Looking back at wastewater samples from that week, it appears the variant was already present in California and New York (Kirby et al. 2022). The signature was in the sewage at least one week before the first clinical case was announced by the CDC on December 1.

Throughout the pandemic, wastewater-based epidemiology (WBE) has generated timestamped samples and novel data on the spread of SARS-CoV-2. These insights will remain critical as the virus continues to evolve. In this article, we outline insights from leading experts on where and how wastewater surveillance technology and infrastructure may play a role in 2022 — both for SARS-CoV-2 and for other viruses.

Wastewater surveillance using Droplet Digital PCR (ddPCR) is a comprehensive, cost-effective, highly sensitive way to detect specific variants of the SARS-CoV-2 virus in communities, allowing scientists and public health officials to monitor spread and take action.

Droplet Digital PCR takes wastewater testing to the next level with the sensitivity and precision needed to reliably detect the presence of specific variants in wastewater samples, even at extremely low concentrations. Using ddPCR for WBE enables scientists to detect virus 6 days before clinical testing at a sensitivity of 1 infected individual in 10,000, which is extremely important because only 32% of infected individuals seek medical attention.

When identifying SARS-CoV-2 variants, ddPCR can accurately discriminate and quantify multiple variants in a sample using a single-well test. Importantly, multiplexing using ddPCR is less prone to artifacts and has simpler data analysis compared to multiplexing using other technologies; therefore, ddPCR can give an accurate measure of the copy number of both wild-type and variant genomes.

COVID-19 and Beyond

“Due to its relatively low per-sample running cost and its non-invasive nature, WBE will likely play an important role in the continuous monitoring of disease incidence…. Samples gathered in the context of WBE will also potentially help identify the emergence of novel COVID-19 variants of concerns and their spread in the community.”
– Mats Leifels, PhD, Research Fellow, Nanyang Technological University

Mats Leifels, PhD, Research Fellow at the Singapore Centre for Environmental Life Science Engineering (SCELSE) at Nanyang Technological University (NTU) in Singapore, expects wastewater surveillance to fill an important epidemiological gap for COVID-19 as direct testing of individuals wanes.

“As we transition from a pandemic to an endemic COVID-19 situation, it is important to maintain the abundance of recently gained insights into the advantages and limitations of WBE. It’s only a matter of time until the enormous clinical-based surveillance infrastructure we have today is scaled back. However, due to reinfection and the emergence of novel strains, the burden of disease associated with COVID-19 will likely not decrease any time soon,” said Leifels. “Due to its relatively low per-sample running cost and its non-invasive nature, WBE will likely play an important role in the continuous monitoring of disease incidence on the municipal level or in susceptible populations, like assisted living facilities. Samples gathered in the context of WBE will also potentially help identify the emergence of novel COVID-19 variants of concerns and their spread in the community.”

Beyond SARS-CoV-2, Leifels believes “WBE has immense potential for low-cost assessment of other zoonotic viral diseases, such as Dengue. In low-resource environments, in particular, such illnesses are difficult to spot due to the lack of clinical infrastructure and symptoms that resemble the common cold.”

“Continuous monitoring of centralized wastewater treatment plants for genome motifs associated with not yet identified viral pathogens can be an important, sensitive, and cost-effective early-warning tool for ‘disease X’ — an illness caused by a yet unknown, most likely respiratory and zoonotic virus capable of causing the next pandemic.”

Expanded Collaborative Networks and Data Monitoring

Colleen Naughton, PhD, Assistant Professor of Civil and Environmental Engineering at the University of California Merced, and Krystin Kadonsky, an Environmental Systems graduate student in her lab, expect to see a broader focus for wastewater surveillance beyond COVID-19 in the coming year.

“A new trend we started to see in late 2021 — but that will influence 2022 — is using wastewater testing for other targets like influenza and respiratory syncytial virus,” Naughton said.

They also look forward to more programs coming to fruition, including national, European, and global networks and data systems. For example, in the U.S., the Centers for Disease Control and Prevention’s (CDC’s) National Wastewater Surveillance System, which recently supported monitoring of 500 more sites across the U.S., is expected to release some of the data submitted to them publicly. Naughton also hopes to see more data from the European Union, which has adopted the Canadian Open Data Model (ODM) for its dashboard.

“The Wastewater SARS Public Health Environmental REsponse (W-SPHERE) global data center also collaborates with ODM, and we hope to further integrate our data forms,” said Naughton. “Regarding technologies, the Water Environment Federation (WEF) has released a Wastewater Testing Challenge for more rapid testing methods for non-lab settings, but this may still take some time to develop and become operational beyond 2022.”

References

Kirby AE et al. (2022). Notes from the Field: Early Evidence of the SARS-CoV-2 B.1.1.529 (Omicron) Variant in Community Wastewater. https://www.cdc.gov/mmwr/volumes/71/wr/mm7103a5.htm, accessed March 4, 2022.

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