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How CU scientists identified coronavirus “super-carriers” by collecting gallons of students’ spit

Two recent studies from the University of Colorado Boulder may have solved a pandemic mystery: Why were so many dorm roommates of COVID-positive students not also getting sick?

Barcodes on saliva samples taken from students, staff and faculty as part of the University of Colorado Boulder's coronavirus testing program are scanned upon arrival in the BioFrontiers Institute COVID-19 surveillance laboratory that processes the samples. (Glenn Asakawa, University of Colorado)
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When the University of Colorado Boulder launched a massive, weekly coronavirus testing program as students returned to campus last fall, it soon encountered a puzzle that shows how much we still have to learn about the virus that has bedeviled us for more than a year.

Students were testing positive, and they certainly seemed capable of spreading the virus. But, in the dormitories — the places feared to be most at risk for large, sustained outbreaks — the transmission chains instead appeared sporadic.

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More than 1,000 students living in dorms ultimately tested positive. But in only 20% of those instances did the infections appear to be the result of transmission from one roommate to another. Instead, contact tracing revealed that most of the dorm infections likely came from off-campus contact.

How were people living in such cramped quarters not sharing the virus?

A possible answer comes from tests of literally gallons of student spit and two new studies from researchers at CU’s BioFrontiers Institute. The studies, one on viral transmission in residence halls and one on the amount of virus found in student saliva tests, were published earlier this month on the preprint server medRxiv, where academics have been posting research during the pandemic that has not yet been peer reviewed.

To learn more about the studies, The Colorado Sun spoke with Kristen Bjorkman, a CU researcher who holds a doctorate in biochemistry from the university and is the university’s COVID scientific director. The following Q&A has been edited for length and clarity.

Colorado Sun: Let’s first talk about where this data is coming from. How does the testing system work?

Kristen Bjorkman. (Provided by the University of Colorado)

Kristen Bjorkman: So before the fall semester started, we basically built this integrated public health system. And that included this weekly screening or monitoring program where we do a saliva-based RT PCR (test) and focus heavily on our residence hall students, because we thought they might be a higher-risk population. … So all of those data are kind of coming together to give this look at what were the COVID dynamics on campus. What level of infection did we see? What level of spread did we see? Where did cases originate, and where did they go when they got here?

Sun: You also did something unusual for a coronavirus test. You didn’t just screen for positive or negative. You also looked at how much virus was in each sample.

KB: The saliva tests are quantitative. And that’s how we are able to get a hold of viral load in our students. … It was never meant to serve as a diagnostic tool, it was meant to rapidly and consistently screen a large portion of our on-campus community, so that we were able to, particularly, identify asymptomatic people. There’s already evidence from around the world that asymptomatic people could transmit, and that younger adults are more likely to be asymptomatic than older adults. We knew that this would characterize our student population. So we thought, “There could be a large reservoir of these carriers, the viral carriers. And we could be blind to them if we’re only relying on people identifying through being symptomatic.”

Sun: What did you find when you dug into the positive test results?

KB: One of the key points was that these students are typically asymptomatic. (But) they can have very high viral load. So just because you’re not displaying symptoms, does not mean that you are carrying less virus. One of the papers, that’s the super-carrier paper, compared the viral load distribution in these asymptomatic students to people who are symptomatic from other studies. The range of viral loads is essentially identical. So you can have just as high viral load as somebody who’s in the hospital. The difference there is that if you’re asymptomatic, you feel fine. So you can be walking around and engaging with the community rather than maybe isolating yourself.

Sun: And you could be spreading the virus.

KB: These asymptomatic people, they can transmit. We did have students transmitting. Most of our cases did originate off campus. But we were surprised, actually, to see how little transmission there was between roommates on campus, because the whole reason we originally were focusing our screening program on the dorm students was because we were worried that there could be rampant spread between roommates and within dorms. And we just didn’t see that. Only about 20% of students who became infected who had a roommate actually transmitted it to their roommate.

So then we wondered why. Was there anything that we could find that correlated with an increased risk of transmitting to your roommate? So like I said this saliva RT PCR test is quantitative. We could look at the viral load. And we could compare, for the people who transmitted, what was their viral load on average, and, for the people who didn’t, what was their viral load. And we found about seven times higher viral load in the students who did transmit to their roommate compared to those who did not. And the paper about super-carriers also showed that we had this really asymmetric distribution of load. So only 2% of the people who were infected carried 90% of the viral load.

Allen Oden, a civil engineering major from Fort Bragg, North Carolina, takes a COVID-19 test at Williams Village at the University of Colorado Boulder. (Casey A. Cass, University of Colorado)

Sun: You’ve used the term “super-carriers” a couple of times to refer to asymptomatic students with these really high viral loads. But how is that possible? How is it possible to have so much virus in your body without it causing you to feel symptoms?

KB: That is an ongoing area of research right now. It’s not completely understood. But it seems like, for some people, it’s almost like, they have the immune system kind of go haywire. Their body just overreacts in some ways. It seems like maybe they’re trying to fight the infection off, and then it ends up damaging their tissues. And in some people that doesn’t happen, and it’s not fully understood why that is. There are some patterns that are emerging as far as characteristics that might be protective in some people versus another. But the real root cause of, like, why is this particular group faring better than this particular group? It’s not fully known. So people are out there investigating everything from genetic factors to behavioral factors that can contribute to this.

Sun: Are there any common characteristics that super-carriers share beyond viral load? Is there any way to know if you’re likely to be a super-carrier?

KB: We don’t know right now. That’d be a future area of investigation, and would be really helpful to learn. Because if there are added identifiers — if you are this, that or that — that can help your health care provider identify that you might be at risk of being a super-carrier, or, if you’re infected, you might end up with really high viral load. But right now, we don’t know.

Sun: How do you know that you’re identifying unique characteristics among students, though? Is it possible you’re just catching infected students at different stages of their infections and the peaks aren’t really all that different?

KB: Absolutely there’s the potential that we’re capturing them at different stages of their infection. But that is also the value of a consistent screening program. So if we look at the data as a whole, we expect that we are capturing people at many stages. If we look at individuals, we often see them multiple times in a testing record, especially since we refer them on to diagnostic tests on campus. So many people do have more than one test on record. But then there are individuals that, for instance, opted in to be part of a deeper research investigation, and we have many samples corresponding to a broader range of their infection. And some of them peaked really high in viral load, and some of them didn’t. So even when you’re kind of intentionally looking across a time course, people can peak at different stages. And there’s other published works out there that see similar things that not everybody peaks at the same place.

The Flatirons in Boulder are a backdrop to Baker Hall, designed in 1937 as a men’s residence on the University of Colorado. The dormitory, with its iconic red tile roof and Lyons sandstone walls, still houses about 500 students each semester. (Doug Conarroe, Special to The Colorado Sun)

Sun: Was this just astounding to you? What did you think when you saw this data start coming in and you began to realize these patterns existed?

KB: It was, in fact. We looked at this so many different ways because we were really nervous, obviously, as many schools were. There were so many unknowns. We had to make choices, and we had to make plans. But every university has a different plan. And so, one possible scenario was, well, once we have infected students on campus, it could just spread through the dorms. It could spread across dorms. That could end the semester early, and that could end up with a lot of infected students who could get really sick. They could impact others. And when we just weren’t seeing that — and that was supported by our contact-tracing teams that said, “Yeah, we’re seeing lots of these infections. They’re not originating on campus from spread on campus; they’re originating off campus” — it was surprising.

Sun: This completely upends one way that we in the public think about the pandemic. When we think about super-spreaders, we think about it in terms of someone’s behavior — that everybody is an equal-opportunity spreader, so it’s all about whether you’re acting responsibly. But you found that it’s way more complicated than that.

KB: Right? You could have somebody with a lot of social contacts, who has a lower viral load, and then maybe you have less transmission. And then you could have somebody who has a lot of social contacts with really high viral load and that kicks off, you know, an outbreak. It can be really diverse across people.

Sun: So what should the public take away from this research?

KB: I think for a lot of people and feedback that I’ve been getting from some students is that they feel reassured that just because they may be diagnosed as infected, it doesn’t guarantee that they’re going to spread it to someone. There’s always that risk, and you should always take a diagnosis seriously. But a lot of people will actually feel a lot of anxiety and guilt, not just fearing for their own health, but for the people around them. So it can give a little bit of hope. I think also a good takeaway for us as a university is we continue to offer on-campus living and roommate pairing. And for a lot of people that brings mental health benefits. There’s also educational benefits that come with being able to be on-campus and be in person.

Saliva samples sit in a cooler before being tested in the BioFrontiers Institute COVID-19 laboratory that processes the samples as part of the University of Colorado Boulder’s coronavirus surveillance program. (Glenn Asakawa, University of Colorado)

Sun: Is this in line with what researchers are finding elsewhere or is CU somehow an outlier?

KB: It is consistent with data that are emerging from around the world. So this kind of 20% rate of transmission in households, there are some other reports that show that as well. They are typically looking at symptomatic people. But that just happens to be a more accessible population for a lot of studies, because in most cases, you don’t have an asymptomatic screening program like we were using. So we add to that literature, but pointing out that this can happen with asymptomatic people. There are multiple studies showing this really vast range — a trillion fold for our students between the highest viral load and the lowest viral load. And so this is something we have to grapple with as we approach this pandemic.

Sun: Wait, did you say trillion with a T?

KB: I did say trillion with a T. So the person with the highest viral load that we identified had 1 trillion times more virus than the person with the lowest viral load that we identified. So when I say vast, it’s vast. … We are looking at, basically, the copies of virus per milliliter. And a milliliter is about two tenths of a teaspoon. So, we can be down in the single digits per milliliter, or we can be up at like 6 trillion per milliliter.

Sun: Wow.

KB: Yeah.

Sun: That’s just mind-boggling.

KB: Imagine all the saliva that’s in our lab right now.