One of the best tools for predicting COVID-19 outbreaks? Sewage.

CICERO, ILLINOISA noxious odor hits me as soon as I step in the Westside fine screening building at the Stickney Water Reclamation Plant—one of the world’s largest wastewater treatment facilities, located outside of Chicago. In this industrial-looking brick building with exposed pipes, conveyer belts, and clunky machinery are chambers carrying raw sewage—mostly from people’s homes—that will be screened to remove plastic, rags, metals, and other debris.

Standing next to me, operations manager Joe Cummings, listens for a whirring sound. “You’re going to hear the pump running,” he tells me, as every five minutes, a thin suction pipe extracts five tablespoons of turbid, dark-gray untreated wastewater. Over 24 hours each day, this auto sampler will empty raw sewage into a five-gallon plastic jar and staff biologists will then test the jar’s contents for toxic minerals or compounds that could harm microbes needed to clean and process the wastewater before its release into the Chicago Sanitary and Ship Canal.

Since March 2020, when the COVID-19 pandemic began, scientists have also been using these untreated wastewater samples to search for fragments of the SARS-CoV-2 virus shed in the feces of infected patients, allowing them to provide early warnings about viral outbreaks. Virus levels typically increase for roughly four to six days in wastewater before an area sees an uptick in clinical cases. Communities and medical providers can therefore use wastewater data to predict local surges and ramp up testing and vaccination efforts.

Early work was so successful that in September 2020 the U.S. Centers for Disease Control and Prevention established a National Wastewater Surveillance System, partnering with dozens of treatment plants across the country and funding wastewater surveillance for SARS-CoV-2. By February 2022 CDC funds were supporting programs at more than 400 sites across 37 states, four cities, and two territories, although the coverage remains patchy. With funding guaranteed until 2025, the goal is to reach all 50 states, says CDC project leader Amy Kirby, and to expand the data gathering to include other viruses such as influenza and norovirus, the food-borne bacteria Escherichia coli, bacteria that have become resistant to antibiotics, and the fungal pathogen Candida auris.

Initially, public health officials were skeptical of efforts to surveil wastewater for SARS-CoV-2, notes Rachel Poretsky, a microbial ecologist at the University of Illinois Chicago. Some were concerned that chemicals in the sewage would degrade the virus’ genetic material, while others doubted it was possible to sequence distinct viral material derived from wastewater.

Poretsky and other scientists proved them wrong. With an independent grant, she and her colleagues worked with the Chicago Department of Public Health to detect and quantify SARS-CoV-2 at Stickney and a few other wastewater treatment plants in the region. “When we were able to show that data [from wastewater] mirrored what was seen in clinical settings or filled holes in our public health infrastructure, people started to lean on it a little bit more,” she says.

Virologist Heléne Norder at the University of Gothenburg in Sweden is among the scientists who have pushed to advance wastewater monitoring research for years. With improvements in molecular sequencing tools, scientists had previously identified influenza A virus, rotavirus, adenovirus, Aichi virus, and astrovirus in wastewater. But Norder says she often found it hard to get her work taken seriously or she struggled to secure funds—until now.

“Unfortunately it took a pandemic to even realize how important and exciting this field of research is,” says environmental chemist Arjun Venkatesan at Stony Brook University in New York.

Deep history of wastewater watching 

One of the earliest successes at detecting pathogens in sewers happened in Belfast, Ireland, which experienced devastating typhoid fever outbreaks in the 19th century. The disease spread when people consumed food or water contaminated with Salmonella typhi bacteria, which were present in the feces of infected individuals. Even after the outbreaks subsided, chronic asymptomatic carriers continued to excrete bacteria in their feces for years. But in those early days, scientists had trouble proving that sewage contamination was a culprit in disease outbreaks.

Then, in 1928 William James Wilson, a professor of hygiene and public health at Queen’s University in Ireland, used a new cultivation technique on samples of sewage on its way to Belfast’s sedimentation tanks. He was able to isolate 21 strains of S. typhi from the samples, providing direct evidence that sewage carried the pathogen.

James Allan Gray at Scotland’s Edinburgh University similarly confirmed the presence of Salmonella paratyphi­—a bacterium that causes a less severe typhoid fever called paratyphoid fever—in seven out 20 sewage samples collected in Edinburgh in 1929. And in the U.S. virologist John Paul at the Yale School of Medicine and his colleagues verified the presence of polio virus by infecting monkeys with sewage samples collected in 1939 in Charleston, South Carolina, where an unusually large number of polio cases had been recorded.

In the years that followed, scientists explored wastewater monitoring as a tool for public health surveillance. Israel, for instance, had been polio-free for six years when an outbreak in 1988 left 15 people paralyzed. Wastewater sampling showed that open sewers were a potential source for virus exposure. Since then, 25 to 30 sites in Israel and adjoining Palestinian territories have collected monthly sewage samples to detect poliovirus before symptomatic cases appear in the community. Such surveillance allowed Israeli authorities to spot the “silent circulation” of wild poliovirus in the country’s sewers in 2013, prompting mass vaccination efforts. Over the last two decades or so, more than 20 countries have adopted the same approach. 

Scientists have also been able to use untreated wastewater to spot other viral outbreaks before people got sick. In Sweden, Norder and her colleagues recorded a 2013 peak in norovirus, dubbed the winter vomiting bug, in sewage samples at least two weeks before most infected patients were diagnosed in hospitals and elder-care centers in Gothenburg. They’ve also detected certain Hepatitis A virus strains in wastewater a few weeks prior to reported clinical cases.

But in many countries and regions, systematic monitoring at wastewater treatment plants has long been lacking. That may change because of COVID-19.

Searching the sewers for SARS-CoV-2

In early 2020 Chinese scientists confirmed the presence of SARS-CoV-2 genetic material in stool samples from an infected patient. Soon afterward researchers in the Netherlands reported the presence of viral RNA in wastewater in their country.

At the Amersfoort Wastewater Treatment Plant in central Netherlands they found SARS-CoV-2 RNA fragments in untreated water six days before the country’s first cases were reported in March 2020. As more people got COVID-19, those fragments became more abundant. The researchers thus proposed sewage surveillance to provide evidence for the presence and circulation of SARS-CoV-2 in the community. That’s particularly valuable when many infections may be mild or asymptomatic or testing may not be easily accessible.

Rolf Halden, an environmental engineer at Arizona State University, was quick to take notice. Since 2018 Halden and his colleagues had been using wastewater monitoring to track opioid consumption in Tempe and sharing monthly updates with the community via an online dashboard. Influenza was next on their list, but they quickly pivoted to look for SARS-CoV-2 as the pandemic hit. In May 2020 his team identified an infection hotspot in Guadalupe—a predominantly Hispanic and Native American town where testing was lacking—sparking a speedy response from community health workers.

Similar success came from analyzing wastewater for SARS-CoV-2 at universities. In August 2020 a team of scientists at the University of Arizona detected SARS-CoV-2 genetic material in wastewater from a dorm, prompting immediate testing and identification of two asymptomatic students, who were then isolated.

Between November 2020 and April 2021 a study using data from New York City found a similar trend in the rise and fall of new COVID-19 cases and virus levels in the city’s 14 wastewater treatment plants. And in November 2021 the city found evidence of Omicron in its wastewater at least a few days before the first case was clinically identified.

As Omicron overtook the Delta variant in the U.S., public health officials used wastewater data to make decisions about when to discontinue treatments such as two monoclonal antibodies that didn’t work against the new variant, says environmental engineer Colleen Naughton at the University of California, Merced, who tracks SARS-CoV-2 wastewater monitoring efforts across the globe.

Experts point out that wastewater monitoring is no substitute for proper testing programs. For one thing, it’s hard to make sense of the absolute quantity of viral RNA in a community from this kind of sample.

“It’s just too complicated to link the virus counts to the number of people who might be infected,” Poretsky says. To do that we instead need to know how many people are shedding the virus and how long they are shedding, and that can vary depending on the variant, the infection trajectory, and people’s vaccination status.

“Even with those limitations, wastewater surveillance can be very useful,” Kirby says.

The future of sewer surveillance

That’s why many experts in the field are now thrilled with the CDC’s commitment to expand wastewater surveillance beyond SARS-CoV-2. But details about the effort and scale of monitoring are yet to be ironed out.

For instance, many wastewater plants collect samples twice a week for SARS-CoV-2 testing. That level of testing may not be necessary for pathogens that don’t change as quickly. Also, some diseases may be seasonal and won’t require year-round testing, while some will be more relevant in certain regions than in others.

Some scientists are proposing a catch-all approach that will look at the full diversity of viruses in urban sewers across the globe. The process would entail repeatedly sampling the same sewers over years to identify viruses that are typical for that region and intervene when that composition changes.

“Depending on how frequent some mutations or viruses are in a sample compared to the global diversity, we could find something that sticks out locally,” says Marion Koopmans, a virologist at the Erasmus University Medical Center in the Netherlands. But tools to easily identify any unknown viruses in a sample aren’t quite there yet, she says. Also, teasing apart human viruses from animal and plant viruses in samples involving novel microbes could be challenging.

Beyond the technological hurdles, wastewater surveillance raises ethical and privacy concerns, especially if the monitoring occurs at a more local rather than community scale. “It’s like digging up your neighbor’s trashcan,” Venkatesan says.

Outside of a serious outbreak, tracing a disease or use of certain drugs back to an individual or a neighborhood could lead to stigmatization. Also doing such work without engaging with the community could jeopardize their trust. “We

have an understanding of the ethical lines for clinical issues,” Kirby says, “but there are no similar guidelines for environmental samples.”

This issue becomes especially important considering growing interest in archiving such samples in case there’s a need to trace outbreaks back to the arrival of certain pathogens.

In the meantime, monitoring efforts continue to evolve. With the recent U.S. surge in monkeypox cases, Poretsky started looking for evidence of the virus in wastewater from the Chicago area. “We don’t have a sense of how much disease there is, whether it's spreading, how long it might have been present before we started looking for clinical cases,” she says. But wastewater may hold clues.