The U.S. is in the grips of a third wave of the coronavirus pandemic and inching toward the possibility of another grim milestone - hitting up to 200,000 cases a day, stated the University of Nevada, Las Vegas (UNLV). It’s a potential reality that makes UNLV researcher Edwin Oh’s work even more urgent: sequencing the RNA of the SARS-COV-2 virus to find targets that make vaccines more effective.
“I can envision a possibility where we create the vaccine, but the virus has mutated to a point in some communities where that vaccine is less effective for people who’ve contracted a different strain,” Oh said, adding, however, that recent vaccine development announcements from Pfizer and Moderna are promising.
Oh’s research program — screening wastewater for the presence of COVID-19 — is made up of postdoctoral fellows and UNLV students. Together with a variety of collaborators in Nevada and in neighboring states, this effort could help inform vaccine development in the future.
In August, Oh’s research group was part of a collaboration led by the University of Arizona to screen wastewater in dorms and buildings around campus to determine whether the virus was circulating. The surveillance program picked up two asymptomatic student cases of COVID-19 and helped prevent a potential outbreak at the start of the fall semester. Oh’s latest endeavor takes it a step further: extract the RNA from the virus and determine if and where different strains of the virus are cropping up in communities around Las Vegas.
“Is the virus that we’re getting in Nevada very, very different from California, or very, very different from Denmark? And over time, how is this virus changing? This would be an inexpensive and efficient program to help us identify communities that might respond far better to certain vaccines that are being developed in the market right now,” said Oh.
The virus - SARS-COV-2 - is what’s known as an RNA virus. This is a virus that enters through the respiratory system and it’s thought to be shed in fecal matter and in urine, so that’s why we and others had this hypothesis that we would screen sewage for SARS-COV-2. What we see in wastewater can predict what’s going to happen in communities by giving us anywhere between a two- to five-day advance notice of the virus’s presence before symptoms begin to show. That’s a decent amount of time for our public health officials to now contact trace within that community to figure out whether something might have been missed.
This is a substance that can be detected in the lab very easily and measure its potency in two ways. One way is by total amount: is there more, or is there less of it? The assumption is that if there’s more of it, then there’s more people shedding it, then more people in that building have it, and therefore, it could be extremely dangerous. The other way is to determine the actual sequence that the virus contains. People have three billion nucleotides in their genome and that makes them who they are; for a virus, all of the features it requires to enter a human cell, for it to replicate in a human, is contained within 30,000 nucleotides. It’s a small fraction of the human genome, but that small genome is sufficient to wreak havoc and kill more than 1.3 million people in the world.
Sequencing can help determine if there’s a mutation within that 30,000 nucleotides that might make it more infectious. There’s been a story going around for some time about how the animals on a mink farm in Denmark could contain a mutation that would make this virus potentially more infectious and that could be extremely dangerous for our population for many different reasons.
The collaborators at the University of Arizona screened the wastewater of dormitories, buildings, and various centers on campus for the presence of COVID-19. They found a positive hit at two different buildings, and this was really interesting because students had just returned to campus, and a condition for returning to campus for the students was to have received a test result of “negative” before coming back. Two dormitory residents who initially tested negative later tested positive, even though they were asymptomatic. These individuals must have contracted this virus during the couple of days that they were on campus.
The realization is that none of this would have potentially been detected if we did not have this surveillance program in play. As a result, these students were isolated and quarantined and they’ve since recovered. A case like this has led to many other similar efforts across the nation, where wastewater surveillance has led to the identification of students and faculty members who had the virus but were asymptomatic. When someone is asymptomatic, it’s so difficult to know.
An interesting caveat to the team’s surveillance program is that they were unable to directly match the viral genomes found in the wastewater to the viral genomes in the asymptomatic students. This is important since they cannot be sure whether an infected out-of-state parent or friend visited the premises for the day and then left. However, their program was not set up to address such challenges and we are now working on the technology to provide more clarity.
Up to this point, the team has been juxtaposing clinical samples from Southern Nevada public health labs with the wastewater samples. They’ve sequenced around 300 samples, and they’re comparing that to six wastewater samples. It’s a very randomized analysis, and they’ve been observing that the variants, or mutations, they’re seeing in wastewater, they also see in humans.
The team also is using their surveillance program to monitor influenza. They want to know the types of influenza strains are present and how widespread these different strains are.
The next step is to do this at a larger scale and bring their sequencing program to additional states. They’re working with collaborators as close as New Mexico, and as far away as Israel. They’re currently applying for a National Institutes of Health grant to harmonize best practices with other U.S. institutions.
