Kara Nelson is a Professor of Civil and Environmental Engineering the Associate Dean of Equity and Inclusion for the College of Engineering at UC Berkeley. Nelson and IGI Scientific Director of Microbiology Jill Banfield are leading a project, tracking the spread of SARS-CoV-2, the virus that causes COVID-19, in Bay Area wastewater.
Why look for a respiratory virus in wastewater?
SARS-CoV-2, the virus that causes COVID-19, infects the intestinal tract of most individuals that have a COVID-19 infection, whether they’re symptomatic or not. People that are infected will shed the virus in their stool and therefore we can pick up the signal in the wastewater. What’s particularly advantageous about sampling wastewater is that it’s an inherently pooled sample, meaning you are testing samples from multiple people at once. So from collecting a single wastewater sample, we can get information that is representative of up to hundreds of thousands of people in a single sample. So it’s a very efficient and effective way to get information on a large population.
It’s also less biased because a lot of people that are infected but are not symptomatic may never get a clinical test, and we may never identify them as a case, but we can still detect the signal in wastewater. So, we get information even from asymptomatic individuals.
What exactly can you look at and measure in the wastewater?
We can see the presence and concentration of the virus using quantitative real-time PCR, which is the same method used to test clinical samples. In this technique, probes that match the virus’s genetic RNA sequence at specific spots are used to make copies of a small segment of the genome. If and how many copies we get depends on how much virus is in the sample to start with.
The challenge for wastewater is that we have to be able to detect that signal in a much more diluted form. When a clinician collects a nasal swab or a saliva sample from an individual, the virus is present in much higher concentrations than in wastewater. In wastewater, it’s being diluted out by many other types of waste and water that go down our drains.
Can you see different strains of virus?
Yes. In addition to PCR-based methods, we are using a newer technique referred to as metagenomic sequencing. With this technique, we sequence all of the genetic material present in a sample, not just a small stretch of one virus. We sift the data to pull out the information that’s useful to us — in this case, the genetic code from the SARS-CoV-2 virus. We can see differences between strains of the virus, even single nucleotide variants, meaning just one RNA letter is changed. So it’s a very high-resolution method, which is really exciting!
Another important advantage of this approach is that, with PCR-based methods, if the genetic code of the virus changes in the probe area, the detection methods will stop working. The metagenomic sequencing approach doesn’t use probes, so it doesn’t have that same vulnerability. And so we will be able to detect changes even if they occur in the probe region, which would let us know that clinical testing protocols might need to be modified.
Does detecting different strains of CoV-2 allow you track transmission patterns?
Being able to detect the specific strains means we can identify when and where strains are being introduced from other regions.
We can also look within a particular community: if the strains are very similar, that would suggest that transmission is primarily happening within a community. If we see different strains being introduced, that suggests that there could be significant transmission due to contact with people outside of the community or travel outside of the community.
So, this is a really powerful tool for being able to understand the transmission patterns and what types of activities pose greater risk.
We can also use this information to evaluate the effect of different restrictions on mobility or changes in quarantine and social distancing guidelines.
What have you uncovered so far from sequencing strains?
Half of the single-nucleotide — that is, change in just one RNA letter — variants that we detected in wastewater samples were also present in clinical samples collected in California.
What about the other half?
We were able to detect strains that have only been identified in clinical samples outside of California, ones reported in other places in the United States and other places in the world.
This indicates that by sampling wastewater, we can identify strains that have been introduced to our region that haven’t yet been picked up in the clinical samples.
So, we actually get a more comprehensive picture — and an earlier signal — of which strains are circulating in a population.
An application we haven’t seen yet but could be important in the future is tracking specific strains of interest. The main use here would be, if the virus mutates in a way that some strains become either more or less virulent, we’d want to be able to track those strains specifically.
Are you enjoying this surge of interest?
I am just overjoyed at how much interest there is in wastewater, because I think about wastewater every day — not just as something disgusting that we flush down the toilet, but actually as a resource, as something that contains a lot of information and that we can also turn into useful products. I have another project where we extract the nutrients from the wastewater that we can use as fertilizer.
Do you think regular surveillance of wastewater will be useful, even outside of pandemic times?
Absolutely. My research team focuses on controlling the transmission of pathogens through water. We have mostly focused on the transmission of known enteroviruses and other viruses, bacteria, and parasites that infect the intestinal tract. The approach of using wastewater sampling to understand the prevalence and transmission of pathogens in a population has been under development for a while, but not in widespread use.
With the COVID-19 epidemic, there’s tremendous interest all around the world in applying this approach to help end the pandemic. I expect that those of us that work on understanding transmission of pathogens via water will continue to develop applications of this approach.
How did you start working in wastewater?
I started working in wastewater because it is this beautiful intersection. If we effectively manage our wastewater, we can contribute to improving human livelihoods and also protecting the environment. These are challenges that exist everywhere in the world.
I love that there’s more that connects us as humans around the world than divides us. And the fact that we all need safe drinking water and produce wastewater is one of those things that ties us all together.
Watch a video of the wastewater testing team in action and read more on the COVID-19 wastewater testing project in this feature from Berkeley News.