Sewage monitoring emerged amid the Covid-19 pandemic as an effective, non-invasive way to track a viral outbreak, and advances in technology have allowed researchers to not only identify but also quantify the presence of particular variants of concern (VOCs) in wastewater samples.
Last year, researchers from Singapore-MIT Alliance for Research and Technology (SMART) made headlines for develop a quantitative test for the Alpha variant of SARS-CoV-2 in sewage, while also working on a similar test for the Delta variant. Previously, conventional wastewater detection methods could only detect the presence of SARS-CoV-2 viral material in a sample, without identifying the virus variant.
Now, a team from SMART has developed a quantitative RT-qPCR test that can detect the Omicron variant of SARS-CoV-2. This type of analysis allows wastewater surveillance to accurately trace the dynamics of variants in a given community or population, and to support and inform the implementation of appropriate public health measures tailored to the specific characteristics of a particular viral pathogen.
The ability to count and rate particular VOCs is unique to SMART’s open source test and allows researchers to accurately determine movement patterns in a community. Therefore, the new test can reveal what proportion of SARS-CoV-2 virus circulating in a community belongs to a particular variant. This is particularly important because different SARS-CoV-2 VOCs – Alpha, Delta, Omicron and their offshoots – emerged at various times during the pandemic, each causing a new wave of infections to which the population was more susceptible.
The team’s new allele-specific RT-qPCR test is described in an article, “Rapid displacement of SARS-CoV-2 Delta variant by Omicron revealed by allele-specific PCR in wastewaterpublished this month in Water Research. The main author of the work is Eric Alm, professor of biological engineering at MIT and principal investigator in the Antimicrobial resistance (AMR) interdisciplinary research group within SMART, the research enterprise of MIT in Singapore. Co-authors include researchers from Nanyang Technological University (NTU), National University of Singapore (NUS), MIT, Singapore Center for Environmental Life Science Engineering (SCELSE), and of the Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna (IZSLER) in Italy.
Omicron exceeds delta in three weeks in Italian study
In their study, the SMART researchers found that the increase in population coverage of the booster vaccine in Italy was consistent with the complete replacement of the Delta variant by the Omicron variant in wastewater samples from the Torbole Casaglia wastewater treatment plant, with a catchment area of 62,722 people. Taking less than three weeks, the rapid rate of this displacement can be attributed to Omicron’s infection advantage over the previously dominant Delta in vaccinated individuals, which may come from Omicron’s more efficient evasion of the vaccination-induced immunity.
“In a world where Covid-19 is endemic, VOC monitoring through sewage monitoring will be an effective tool for tracking variants circulating in the community and will play an increasingly important role in guiding the response. public health,” says paper co-author Federica Armas, senior post-doctoral fellow at SMART AMR. “This work has demonstrated that wastewater monitoring can be used to quickly and quantitatively trace VOCs present in a community.”
Wastewater monitoring is vital for future pandemic responses
As the global population becomes increasingly vaccinated and exposed to previous infections, nations have begun the transition to classifying SARS-CoV-2 as an endemic disease, shifting active clinical surveillance back to rapid antigen testing decentralized and therefore reducing the sequencing of patient samples. However, SARS-CoV-2 has been shown to produce new COVs that can quickly emerge and spread rapidly in populations, displacing previously dominant virus variants. This was seen when Delta moved Alpha around the world after the first emerged in India in December 2020, and again when Omicron moved Delta at an even faster rate after its discovery in South Africa in November 2021 The continued emergence of new COVs therefore requires continued vigilance on the surveillance of circulating SARS-CoV-2 variants in communities.
In a separate summary document on wastewater monitoring titled “Making waves: SARS-CoV-2 wastewater monitoring in an endemic future,» published in the journal Water Research, SMART researchers and collaborators found that the utility of wastewater monitoring in the near future could include 1) monitoring the trend of viral loads in wastewater for quantified viral estimates circulating in a community; 2) source sampling of wastewater—for example, taking samples from particular neighborhoods or buildings—to identify neighborhood and building-level infections; 3) integrate wastewater monitoring and clinical monitoring for cost-effective population monitoring; and 4) genome sequencing of wastewater samples to track circulating and emerging variants in the population.
“Our experience with SARS-CoV-2 has shown that clinical testing can often only paint a limited picture of the true extent of an outbreak or pandemic. With the prevalence of Covid-19 and the anticipated emergence of new variants of concern, qualitative and quantitative data from wastewater monitoring will be an integral part of a cost-effective and resource-efficient public health surveillance program, allowing authorities to make more informed policy decisions. adds corresponding author Janelle Thompson, associate professor at SCELSE and NTU. “Our review provides a roadmap for the wider deployment of wastewater monitoring, with opportunities and challenges that, if addressed, will not only enable us to better manage Covid-19, but also societies. future-proof for other viral pathogens and future pandemics.”
Furthermore, the review suggests that future wastewater research should adhere to a set of standardized wastewater treatment methods to reduce inconsistencies in wastewater data for improved epidemiological inference. . The methods developed in the context of SARS-CoV-2 and its analyzes could be of invaluable interest for future wastewater monitoring work on the discovery of emerging zoonotic pathogens – pathogens that can be transmitted from animals to humans. humans – and for the early detection of future pandemics.
Moreover, far from being limited to SARS-CoV-2, wastewater monitoring has already been adapted for use in the fight against other viral pathogens. Another article from September 2021 described a progress in the development of effective wastewater monitoring for dengue, Zika and yellow fever viruses, with SMART researchers successfully measuring the decay rates of these medically important arboviruses in wastewater. This was followed by another review paper by SMART published in July 2022 which explored current progress and future challenges and opportunities in wastewater monitoring for arboviruses. These developments represent an important first step towards establishing arbovirus sewage surveillance, which would help policymakers in Singapore and beyond take better-informed and more targeted public health action to control outbreaks of arboviruses. arboviruses such as dengue, which is a major public health problem in Singapore.
“Our lessons learned from using wastewater monitoring as a key tool during Covid-19 will be crucial in helping researchers develop similar methods to monitor and control other viral pathogens and future pandemics” , says Lee Wei Lin, first author of the latest SMART paper and researcher at SMART AMR. “Sewage monitoring has already shown promising utility in helping to combat other viral pathogens, including some of the world’s most prevalent mosquito-borne diseases, and there is significant potential for the technology to be suitable for use against other infectious viral diseases.”
The research is led by SMART and collaborators at SCELSE, NTU and NUS, co-led by Professor Eric Alm (SMART and MIT) and Associate Professor Janelle Thompson (SCELSE and NTU), and is supported by the Singapore National Research Foundation (NRF) under its Campus of Excellence in Research and Technological Enterprise (CREATE) program. The research is part of an NRF-funded initiative to develop sewage-based surveillance for rapid outbreak detection and response in Singapore.
SMART was established by MIT in partnership with NRF in 2007. SMART is the first CREATE entity developed by NRF and serves as the intellectual and innovation hub for research interactions between MIT and Singapore, undertaking research projects cutting-edge research in areas of interest to Singapore and MIT. SMART currently includes an Innovation Center and five interdisciplinary research groups: AMR, Critical Analytics for Personalized Medicine Manufacturing, Disruptive and Sustainable Technologies for Precision Agriculture, Future Urban Mobility, and Low-Energy Electronic Systems.
The GRI AMR is a translational research and entrepreneurial program tackling the growing threat of antimicrobial resistance. Leveraging talent and converging technologies in Singapore and MIT, they are tackling AMR head-on by developing multiple innovative and disruptive approaches to identify, respond to, and treat drug-resistant microbial infections. Through strong scientific and clinical collaborations, our goal is to provide transformative holistic solutions for Singapore and the world.