Researchers at UCSD prepare a robot sampler that collects wastewater from the university sewage system. Credit - Caroline Sheikhzadeh
If you’re a student or a faculty member who spends any time on the University of California, San Diego campus, you may know a lot more about what’s in your pee and poop—and that of your colleagues—than you might care to admit.
Members of the UCSD community can download an app that tells them the COVID-19 status of the wastewater generated in the buildings where they spend the most time. In fact, it offers quite a bit of additional detail too, telling users whether any disease-causing microbes are flourishing in that sewage. If the COVID-19 virus is detected, campus regulars get a notification that they might be either infected or exposed, and they are urged to get tested.
The system has already helped to reduce COVID-19 cases dramatically on campus, from 80-90% of wastewater samples testing positive for the virus between Thanksgiving and January, to only 5% in recent months. The sampling “really gives us an unprecedented ability to track the pandemic day by day as the waves of cases go up and down on campus,” says Rob Knight, professor of pediatrics, computer and engineering and director of the center for microbiome innovation at UCSD.
Not only that, but Knight and his students were also able to use wastewater samples to zero in on people who were likely infected with the virus, but asymptomatic. They placed robots to sample wastewater from individual buildings in sewage pipes before they joined a common effluent, and by last September, they were able to note when samples from a specific building went from negative to positive, and then test everyone frequenting that building to identify the positive case, remove that person from the building, and then keep testing samples to ensure they turned negative again. “Being able to take a whole building, determine which person has COVID-19, remove that person from the building, and see the signal drop back down to zero—that exceeded our wildest dreams,” Knight says. He’s since conducted similarly successful analyses of wastewater in San Diego County to predict upcoming surges of COVID-19 infections.
Waste—or more specifically, wastewater—could be the sleeping giant in the universe of disease detection. Because viruses like SARS-CoV-2, which is responsible for COVID-19, are generally shed in human waste, wastewater is proving to be a harbinger of future clusters—if not exactly as pleasant to manage as the proverbial canary in the coal mine, at least a practical warning of cases to come.
Making the case for wastewater
The U.S. Centers for Disease Control and Prevention (CDC), for example, has turned to wastewater surveillance to help monitor SARS-CoV-2 infections, and specifically new variants that might be gaining ground in certain communities. Not only can the virus be detected in waste, but once found, researchers can genetically sequence the culprit to figure out how much it has mutated.
Knight’s team is among many that have documented evidence that SARS-CoV-2 can be detected in sewage several days before cases are reported by testing in humans. Early on in the pandemic, researchers sampling wastewater in northern Italian towns found SARS-CoV-2 in sewage weeks before the first cases started flooding hospitals.
Last spring, in the college town of LaCrosse, Wis., Paraic Kenny, director of the Kabara Cancer Research Institute of the Gundersen Health System sequenced the virus he picked up from samples from the nearby municipal waste-treatment plant and compared them to positive samples from people frequenting bars and restaurants in the area last summer, when there was a known surge of the virus. They found that the samples genetically matched, meaning that the virus was picked up in the wastewater from infected people who had been spreading the virus for weeks before the first cases were confirmed through testing.
And last spring, the Massachusetts Institute of Technology startup BioBot, the first commercial company to provide wastewater analysis for public health applications, began offering COVID-19-related services for communities. The demand for the company’s services is growing quickly; BioBot now samples and analyzes sewage for 100 communities across the U.S.
“In principle, an approach like this can be used to not just ascertain how much virus is in the community, but maybe give hospitals and public health departments a warning of when to anticipate a surge in cases,” Kenny says.
That idea is gaining ground especially in relatively contained communities like schools, college campuses or small cities where getting a heads up that the COVID-19 virus is in the area could lead to better mitigation and control measures to shut the pathogen down. “Over the course of this pandemic, the entire world has seen how valuable wastewater epidemiology is as a tool,” says Newsha Ghaeli, president and co-founder of Biobot. “Our long-term vision is that wastewater epidemiology becomes a permanent part of the infrastructure embedded on top of sewage systems across the country and around the world.”
Before COVID-19, Biobot focused on trolling municipal sewage treatment plants for traces of opioids to help local public health officials concentrate resources and treatment programs where they would have the most impact. But convincing people that analyzing pee and poop would be a worthwhile investment was an uphill battle, Ghaeli says. “Our vision was to create a tool to enable public health to be more proactive, more data-driven, and more equitable, and there wasn’t as much buy-in into that vision as we see today.”
Two primary changes led to this shift. First, Biobot conducted a pro bono demonstration in March 2020 for 400 communities that proved, with real data, the power of wastewater analysis for protecting public health. Second, COVID-19 hit.
In some ways, the pandemic gave wastewater epidemiology the opportunity the fledgling surveillance strategy needed to legitimize itself. In February 2020, scientists documented for the first time that SARS-CoV-2 could be detected in the stool of infected people. Within weeks, Ghaeli and her partners at MIT and the Harvard School of Public Health, developed a way to pick up the virus in sewage and became the first to detect SARS-CoV-2 in wastewater.
Because sewage is an amalgam of all types of human waste, the challenge for any scientist keen on analyzing it is to develop the right probe for snatching out just what they are looking for. It’s a matter of developing the right filters to progressively weed out the true waste from the virus they’re looking for. At UCSD, Knight’s team has refined and streamlined the process with the help of magnetized tracers that they use as probes to attach to SARS-CoV-2 in the samples to pull out the virus. The innovation means that the process of filtering out any SARS-CoV-2 that might be present in a sample of sewage is cut down from 10-12 hours (or overnight) to half an hour.
Biobot works mostly with sewage treatment plants that serve large populations, and takes advantage of existing sampling systems in such facilities. The company sends treatment plants a sampling kit similar to those used by genetic-testing companies like 23andMe—except in this case, the kits are for 150 ml of sewage, rather than a bunch of saliva. The sample is overnighted to the company’s labs in Cambridge, Mass., where technicians run genetic sequencing to search for specific, short sequences of the virus’ genome they know are unique to SARS-CoV-2. “If there is one infected person in a population of about 6,500, we can detect it,” says Ghaeli. The company then provides a detailed report of the amount of SARS-CoV-2 in the wastewater, including comparisons to nearby communities if that information is available.
From local to nationwide
Depending on how extensive and quick COVID-19 testing is in the area, the wastewater analysis can also reveal the presence of COVID-19 days before the cases are confirmed by human-sample testing. That’s especially powerful since studies show that people infected with the SARS-CoV-2 tend to shed more virus at the beginning of their infection than they do later on. If these infected people were not identified until they developed symptoms and then went to get tested in the typical ways, they could be spreading the virus to others during that critical early period, meaning it’s possible the virus is well entrenched in a community before it’s detected.
“We don’t feel wastewater epidemiology should ever replace or be seen as an alternative to clinical testing,” says Ghaeli. “But rather it’s used best to make clinical testing more effective and efficient and better target testing.” Rather than doing blanket testing of, for example, all of an office building’s employees or everyone on a college campus on a regular basis, the signals provided wastewater could identify early on where cases are more likely to be, and direct officials towards the places where they should be doing more extensive testing.
Wastewater analysis could also be crucial to detecting the presence and growth of new variants of the virus, which in turn could signal the need to ramp up prevention measures or consider changes in treatments or vaccines. At least, that’s what the CDC is counting on when it launched a nationwide wastewater surveillance program for public health departments, last September. Currently, 33 states, four cities, one county and three U.S. territories can upload their wastewater surveillance data and get support from data analytics teams at the CDC to interpret them and figure out, for example, the speed at which the virus is spreading through a community—potentially forestalling an outbreak—or whether new variants are emerging.
Such programs are a new way of tracking disease that’s still getting established. “The National Wastewater Surveillance Program did not exist prior to COVID-19,” says Amy Kirby, the program lead at the CDC. Kirby says that when scientists confirmed that SARS-CoV-2 was shed in urine and fecal matter, and when studies showed wastewater could detect the virus anywhere from four to six days before cases were confirmed by COVID-19 testing, the agency decided to exploit the field as an early warning system. “The four- to six-day lead time is really valuable,” says Kirby. “It’s enough time to really make a difference.” Kirby also notes that the wastewater approach brings a universality to pathogen surveillance. “Whether or not you go to the doctor and get tested, or whether testing is even available in your community, none of that matters for wastewater surveillance,” says Kirby. “As long as most people go to the bathroom—and 74% of U.S. households are connected to the sewer system—those communities can get good data.””
Throughout the surge of cases last spring and summer, the CDC was collecting and analyzing wastewater data in pilot programs with a handful of health departments around the country. In one example, as the number of cases began to rise last spring, some health officials weren’t sure whether the increase was due to an actual rise in new infections, or whether enhanced testing, and hence potential false positives, was simply logging more cases. Wastewater data confirmed that indeed the levels of virus in the communities in question were also rising. “We were able to say, no, this isn’t a factor of increased testing in the area, but more likely a true increase in cases,” says Kirby.
Australia, as well as European countries like the Netherlands, U.K., France, Spain and Switzerland also have national surveillance systems in place to scan wastewater for signs of the virus. Even countries with less consistent municipal sewage infrastructure such as Thailand and are turning to the system in rural areas as a way to get ahead of the virus if testing isn’t as available or widespread.
The hurdle to relying more heavily on wastewater surveillance isn’t so much the sequencing and detecting of the virus, but setting up the infrastructure needed to collect samples, process them and interpret the results. “Our health departments aren’t used to using this type of surveillance data,” says Kirby of the early U.S. efforts. “So the challenge was developing the infrastructure to develop a data repository to receive the data and provide the robust analysis for reporting back to the health departments in a way they can use.”
As part of the national surveillance network, the CDC created the Data Collation and Integration for Public Health Response Platform, (DCIPHER), a standardized database for dumping the genetic analysis from wastewater and turning it into actionable policies. For example, some communities are using the DCIPHER data from their sewage to predict where they might need to concentrate testing efforts in regions where more virus is showing up in waste, or when they might expect mini surges in demand for hospital care so health care systems can redistribute personnel and resources.
For the CDC, the next step is ensuring the current national network survives beyond COVID-19 so public health experts can use it to keep tabs on potential future pathogens. One potential challenge on that front is that, currently, the sequencing of the wastewater samples is primarily being churned out by academic and commercial labs that the CDC has partnered with—but there’s no guarantee that the government will be able to retain these partnerships. “That’s not a sustainable model for the long term,” says Kirby. “We want to bring this wastewater testing capacity into public health labs which are built for surveillance testing.”
If that happens, sewage surveillance could alert public health officials to new variants of viruses like SARS-CoV-2 before they start causing disease.
As more scientists become familiar with analyzing wastewater, the more information it will likely yield and the more powerful it will become as a tool for fighting infectious diseases in the future. The CDC fully anticipates that the NWSS will serve as a foundation for a public health disease-detection network that would raise an alarm when it identifies not just COVID-19 and any new viral variants behind it, but other public health threats as well. Given how valuable wastewater surveillance is proving to communities around the country, Kirby and her team at the CDC are optimistic that the agency will continue to invest in the strategy, so the next coronavirus, or other pathogen that threatens human health, can be picked up and managed more quickly—thanks to something as mundane as our pee and poo.