How testing international travelers helps the CDC keep tabs on new variants

Last month, the CDC started publishing data from a surveillance program focused on international travelers coming into the U.S.

In the program—which is a collaboration between the agency’s Travelers Health Branch, biotech company Ginkgo Bioworks, and airport wellness company XpresSpa Group—travelers at four major airports can volunteer to be swabbed right after they get off the plane. The travelers’ test results are pooled by country of origin, meaning that analysts at Ginkgo combine their samples and PCR-test them together.

In addition to test positivity, Ginkgo also sequences the samples to identify variants spreading around the world. The program has included about 60,000 people between November 2021 and September 2022, according to the CDC. It’s now expanding to add more airports, with the CDC and Ginkgo working together to select international flights that should be targeted for testing.

Earlier this week, I talked to bioinformatics experts Andy Rothstein and Casandra Philipson, who work on the CDC travel surveillance program at Concentric (Ginkgo’s COVID-19 testing initiative), to learn more about how the program works. Swati Sureka from Ginkgo’s communications team also took part in the interview.

Here are a few key insights I learned from the conversation:

• Travelers who volunteer to be tested don’t actually receive individual results back from Ginkgo, due to the company’s pool testing method. But they receive free at-home tests that can provide individual results.
• Despite a relatively small sample size, the surveillance program tends to match global coronavirus variant trends from GISAID (a global repository of variant sequences).
• The CDC uses data from this program as a complementary surveillance system, in coordination with the agency’s domestic variant surveillance, wastewater testing, and other systems.
• Along with expansions to more airports, the Concentric scientists are working on testing wastewater from airplanes as another way to pull COVID-19 data from international travelers.
• The experts named BQ.1 and BQ.1.1 as the most concerning variants they’re following right now, though the program has also picked up XBB.

 This interview has been lightly edited and condensed for clarity.

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Betsy Ladyzhets: I wanted to start by asking about the backstory behind the traveler-based genomic surveillance program. I’ve read a bit about it, but I’m curious to hear from you guys about how it got started and choices that have been made as you’ve expanded the program.

Andy Rothstein: Gingko has long recognized that biosecurity is an integral component to the growing bio-economy, even before COVID. But when spring 2020 came around, Ginko as an organization rapidly responded with a large commitment to the sequencing effort across the country… That really showed that there was an opportunity to grow a biosecurity business unit within Gingko, which became Concentric.

We built a K through 12 testing program, where we implemented this novel approach of pooled testing. We could have kindergarteners basically swabbing their noses in the classroom, everyone could put it one tube, it simplified the process, and we were able to get those results out quickly. But we really recognized that this is just one interface that can be a part of the biosecurity infrastructure. 

We saw that travelers were this really important sentinel for bringing in new things like variants or tracking lineages. And we could combine the pooled testing approach with our sequencing capability at Ginkgo. Then, we got in contact with XpresSpa [now XpresCheck], which was pivoting their business model as well, because no one was going in the airports for manicures and massages. We approached them, as well as the CDC branch that deals with travel histories, quarantining, and things like that. We came to them to launch a pilot program in September 2021 as a proof of concept to say like, “Is this an interface that could provide valuable insights for public health and the CDC?”

We didn’t really know whether or not the pilot would work out. But we were one of the first to detect Omicron coming into the country in November [2021]. The program has now expanded, as of August 2022, into a two year program. And we’ve consistently been able to show that there’s real value in early warning, early detection through this novel interface.

Casandra Philipson: Gingko is an organism engineering company, we know that we’re going to be living with engineered organisms in the future. I think, because of that our founders have always had this prerogative to be able to have an early warning system or anomaly detection system for threats, whether or not they’re natural or manmade. And we have a lot of really smart people who had previous experience, in, like, Department of Defense surveillance exercises in the past. So I think there was an interest in early warning signals.

It’s also hard to be able to do surveillance in other countries, at least at that early, pandemic phase. And so this was a really easy way to have access to things that were coming in from other countries, that we otherwise wouldn’t have had access to.

BL: Yeah, that makes a lot of sense. I’m curious, building off of that, how is the CDC using the data that comes out of this program? Is it mostly about new variants? Or are there other things they’re kind of doing with it?

AR: CDC has a lot of complimentary surveillance systems ongoing, especially for SARS-CoV-2, that they’ve built up, whether it be clinical or whether it be wastewater. This is a novel interface for them to be detecting new things coming into the country. And so we really help source and, I guess, consolidate what is coming into the country and whether or not it’s a bad thing, or part of the existing evolution of SARS-CoV-2.

We work in tandem with them weekly, to not only optimize this program, but also give insights into the data that’s coming out. The [travel surveillance page of the] COVID Data Tracker has been a good culmination of all of this work that we’ve been doing. We can broadcast that publicly and show, almost side-by-side, here’s what’s happening in United States; here’s what’s happening, potentially coming into the United States.

BL: I did want to ask more about that new page on the COVID tracker, because I’m curious what you would want the average viewer to take from those charts.  What should folks be getting out of both the test positivity rate and the variants?

AR: The first part is this test positivity rate. What we’ve seen is that, as testing declines in countries around the world, whether that’d be the appetite for testing or the funding for testing, we have a new sentinel to see what, potentially, the positivity looks like around the world. There’s been a number of times that we, in our program, have matched positivity rates in a country of origin [for a group of travelers]. Then as testing stopped [in that country], we still are picking up a positivity rate. For the public that is looking at this chart, it’s an opportunity to see into the window: What’s the global picture of what’s coming into this country?

Positivity is the first lens of data. The next is that we actually sequence, and we are understanding what is the breakdown or the frequencies of different variants coming into the country. You can see how what’s happening on [the CDC’s U.S. variant surveillance page] is lining up with the frequencies in our program. And because we’re finding new things, we end up sort-of being ahead of the curve in terms of what those frequencies might end up being in the United States.

BL: So you’re talking about comparing the CDC’s variant proportions estimates versus the travel estimates.

AR: Yeah, exactly. And the wastewater estimates… Not everybody is necessarily going and seeking testing when they’re sick with COVID, they might be doing an at-home test. So we’re using all of those [data systems] in a complementary sense to find, like, what’s a holistic picture of the SARS-CoV-2 coming in and outside of the United States?

BL: I also wanted to ask about, so like, if I’m a traveler coming into the U.S. at one of these airports where you have this program, how is it advertised? And what do people learn about it when they decide to volunteer to get tested?

AR: We have these pop-up testing booths, in collaboration with XpresCheck. They’re our on-the-ground infrastructure to basically be recruiting folks coming off of international flights. All the international flights go into one bottleneck where you’re going to leave the terminal, and you have an opportunity to see this booth that has some information about like, testing for public health, with the CDC logo—basically recruiting folks to come in. Folks that volunteer, they swab their noses and then we are pooling [tests] by those countries. We also have been giving them free, individual tests to take home.

We’re not collecting or giving back individual testing data to [the volunteers]. But we are showing that this is a part of the public health program. What we’ve found, through survey results, is that participation has really been increased by the fact that people feel like they’re being a part of this public health program and they want to help. We have great recruiters on the ground.

BL: So people don’t get their individual results, but you said they get an at-home test that they can use?

AR: Yeah. And then they can get their individual results [from that test]… They don’t get the pooled result.

BL: Are the data that you’re getting from this program linked to any other data? Because I know one big concern with variants is like, is a new variant going to be more severe? Is it going to be more likely for people to be hospitalized? So is there any capacity to link the tests that you’re doing with, say, hospitalization records?

AR: I think it’s a great idea, a great direction. Right now, we haven’t been linking those clinical data… We can try to look at the data within our program, and then contextualize it [using other sources] on what might be happening, in the United States or in origin countries.

But we’ve also been really excited about expanding our passive detection through wastewater. We’ve done an R&D project where we were looking at wastewater testing off of aircraft. So, that’s another complimentary data set off of the aircraft itself to help get a more holistic picture—not everyone is going to be using the bathroom [on the plane], but not everyone is going to be volunteering in this program. 

BL: Testing the wastewater off the airplane seems like a great idea, I would not have thought of that.

AR: Yeah, we’re really excited about the opportunity to do something along those lines, since folks aren’t always going to volunteer to swab their nose.

We’re pooled testing by country, so we know that folks are coming from specific places. We can also—they can volunteer to give us any past travel history, so that we can try to link those data on our own. But there’s no systematic way to link [our results] to clinical data.

CP: Our sweet spot is microbes and viruses. So we actually don’t collect individual data that would allow us to associate an individual with their health record at all. I just wanted to emphasize that.

BL: That makes sense. I know that [linking datasets] is something that is very challenging to do, even with established health systems. I was just curious.

Swati Sureka: I can add one thing, just in terms of the knock-on benefits of the program. Say we do get early warning of an emerging variant that could potentially be of concern, that we don’t know on the global stage yet. We work directly with the CDC on getting them access to those [test] samples so that they can do direct viral characterization. Because, with emerging variants, it’s hard to get your hands on samples of it to be able to conduct research on how the virus behaves. I think that’s one of the side benefits, being able to actually pull those samples and share them directly with the CDC.

BL: Are there any variants that you’re all particularly watching right now? Like, I know, there’s been a lot of news about XBB, that’s spreading in East Asia. From your perspective, what are you seeing as concerning hotspots at the moment?

AR: Yeah. This is a big part of what our team does: as this data comes in, understanding what might be the trends happening globally. We have repeatedly shown that we can do early warning, [our data are] some of the first to identify a variant of concern. We can look and say, like, there’s certain mutations that we know, either from past variants or in predictive space, that [indicate this new variant is] going to be a problem for immune escape.

Variants that I think we’ve been really keeping an eye on and telling our CDC partners about are BQ.1 and BQ.1.1, which have been split out by CDC in the last couple of weeks. Our program was one of the first to identify and actually designate this BQ.1 variant. So we saw, early on, that it had characteristics because of its mutational profile [allowing it to] take hold. We continue to watch that.

The United States has been, pretty much, a few weeks to a month behind trends that we see in Western Europe. So I think it’s been pretty clear that BQ.1 is going to be something to watch for, as it sort of expands in its frequency… We also see XBB in our program, we’ve seen it as well. I think it’s going to be an interesting new chapter of SARS-CoV-2 evolution where we have potentially co-circulating variants of concern that have different dynamics in different parts of the world.

BL: Yeah, it’s very interesting… One other thing I wanted to ask you about is sample size. It seems like, from the data on the CDC dashboard, that you’re working with a small number of airports and a limited sample, compared to the number of international travelers coming into the U.S. So how do you think about analyzing that, and potentially expanding the sample?

AR: Definitely part of our plan is to ramp up the number of samples that we can get, as well as the number of airports that we might be operating out of.

But I think it’s just remarkable to talk about this program, when you see such a small sample size, and we’re still able to find new things and match GISAID, or global variant frequencies. It highlights, even with a small sample size, that the way that we’ve designed the program and the way our CDC counterparts think about where we’re going to be, what flights are we going to be choosing—that has been really, really successful so far. You always want more samples in science, but I think we’re working with what we have, and we’re excited to be expanding.

BL: That makes sense. So you’re able to say, “We want to send people to these flights, because this country has concerting variants right now,” that kind of thing?

AR: Yeah. Our CDC counterparts are tapped into both the CDC-wide conversations about variants and the global, WHO conversations about variants. So they’ll give us indications when there might be something to think about. And, again, this program is super nimble in its ability to pivot. When we think we want to focus on certain regions of the world, [we can recruit from specific flights].

It’s nice to be working in airports that have these direct flights and these long-haul flights. But thinking about how we prioritize is definitely—the CDC folks are thinking about this, and we sort-of help support them.

BL: The last main thing I wanted to ask about is, obviously in the U.S. and globally, we’re seeing so much less PCR testing now than we had at earlier points in the pandemic. How are you and—to any extent that you can talk about it—how are partners at the CDC thinking about making sure that we’re collecting a lot of samples from diverse settings, and looking in different places, looking at wastewater, and just continuing to keep track of what variants are circulating?

AR: I think back to, finding novel places to sample things. Like, the fact that we’ve invested and tried to build capability to do aircraft wastewater testing is just adding a complementary [data layer]. We’re going to have this layered interface or layered system where we might have some PCR tests, we might have wastewater, we might have sequencing, we might not have sequencing.

We’re figuring out, how do we just keep adding and keep building on this biosecurity infrastructure. I mean, the worst thing that could happen from this is we build all this and then no one uses it again, until something pops up. We’re really invested in finding new and novel ways to sample and to detect, and eventually sequence if we can get more robust data, like on variants.

BL: That makes sense. I wonder to what extent it can one day be useful for other viruses, too. I know we’re in a bad flu moment right now, or at least the beginnings of maybe a more intense flu season this year. And I know experts always talk about, like, “Can we read the tea leaves from the Southern hemisphere?” So that makes me think, “Okay, could we actually sample people who are coming in? And see if they have the flu, and not just COVID?” Or other things of that nature?

CP: This is something that keeps me up at night. Without being too forward-looking, absolutely, I would say, there are some commercial products out there right now—like from Illumina, which is a massive sequencing behemoth, they’ve just released some new sequencers on their end. They have this panel of, like, 66 viruses that you can detect in one panel. I think we’re gonna see more of that from many different types of partners who are looking at surveillance.

Moving beyond SARS-CoV-2, could samples be used for that? We’ve seen lots of publications that definitely prove that’s true. I think it’s right on cue, hopefully, with where we’re all headed.

BL: Yeah, I hope so. Well, those were all my main questions. Is there anything else you all think would be important for me to know about the program?

Swati Sureka: Stepping back, seeing how this [program] has played out over the past year, I’ve just been floored by, like, tens of thousands of people who have mobilized and participated and given samples in service of public health. For me, as a person who works in the communications space, I think we often hear a lot of these narratives of like, “People aren’t gonna do anything” or take any measures that they’re not forced to do.

People are inherently self-interested in all of these narratives that we hear. And it’s been really impressive to watch the participation that we’ve seen from travelers who want to help public health and want to help stop the spread, want to help pick up new variants. I don’t want to lose that thread of things.

BL: Totally. I can just envision, if you’re coming off a long flight, you just want to get through customs and get home. Taking a few extra minutes to get swabbed is not nothing.

AR: Yeah. And you could be doing that and say, “Oh, it doesn’t matter.” But we’re consistently seeing how helpful this data is, to inform all these complementary systems for building a biosecurity infrastructure. It’s really important data as we move forward.

BL: Yeah. When folks sign up, do you give them a link to the dashboard?

AR: Now we do. Now we can, right, it’s now live. It’s been really nice to have that public-facing thing, so that folks know where their efforts are going towards.

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