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This is the program we wish we had in airports two years ago

A voluntary program from the CDC, XpresCheck, and Ginkgo Bioworks detected emerging variants among arriving international travelers

Photo by Bao Menglong on Unsplash

Passengers are no longer required to show a negative COVID-19 test to enter the US, but as the summer travel boom has shown, there still exists a major gap in the assortment of pandemic mitigation measures that have been deployed over the past two years: travelers.

We live in a connected world, and air travel remains one of the most likely ways a new variant — or a new pathogen, like monkeypox — will enter the country from another place.

Photo by JESHOOTS.COM on Unsplash

We need new public health tools and measures to keep pace with disease outbreaks and enable early detection of pathogens, especially measures that can be strategically deployed at airports. This is the pathogen monitoring infrastructure we wish we had in place two years ago, and as testing nationwide wanes but cases mount, it is even more critical to keep these types of monitoring programs in place.

Earlier detection of new variants and pathogens allows researchers, public health officials, and other key stakeholders to gather necessary information about transmissibility, virulence, and medical product countermeasure effectiveness to help mitigate the risk of us being caught off guard again.

The COVID-19 pandemic has shown us how valuable early detection can be, as the virus continues to evolve and we learn even more about its long-term effects. I believe that airports are a great place to gather data about circulating pathogens, and we can use this information to create forecasts about the next steps of an outbreak. Through proactive detection, we can be more prepared, potentially thwarting the next outbreak before it becomes a pandemic.

In a new paper published in the journal Clinical Infectious Diseases, my co-authors and I offer a proof of concept for such an early warning detection system. We report the results of a traveler-based genomic surveillance program that was able to detect new SARS-CoV-2 variants that were coming into the country weeks before community transmission was observed. This includes the first identification of Omicron sub-lineages BA.2 and BA.3, which at that time (December 2021) had not yet been seen in the United States and North America, respectively.

An illustration of “pools” of travelers in Concentric circles.

In collaboration with the Centers for Disease Control and Prevention (CDC) and XpresCheck, we implemented a program at Newark Liberty International Airport, John F. Kennedy International Airport, and San Francisco International Airport for travelers arriving from India, where the Delta variant was first identified. Having this program already in place enabled us to pivot quickly and immediately begin monitoring for Omicron in the weeks that followed.

In late November, we expanded the program to include Hartsfield-Jackson Atlanta International Airport and offered testing to travelers arriving from additional countries, including countries where Omicron was first detected. We implemented a pooled testing strategy, where travelers could opt-in and provide samples that are grouped together for testing — this is an efficient way to sample a larger number of passengers, while conserving resources and maintaining sensitivity.

Photo by Robert Bye on Unsplash

All of the pooled samples went through reverse-transcription PCR testing, which determined the presence and quantity of three different SARS-CoV-2 gene targets. After November 27, when the Omicron variant had emerged and scientists had identified that the S-gene was largely absent from many Omicron RNA samples, we also began evaluating our samples for S-gene target failure (SGTF) within the PCR assay to give early warning of potential Omicron samples.

We then conducted whole-genome sequencing of the virus in all positive samples to get a picture of the viral variants entering the country through airports. We used two sequencing methodologies to determine the variant sublineages: Illumina sequencing for high-fidelity whole-genome analysis and sometimes, when a sample showed SGTF, expedited Oxford Nanopore sequencing to confirm the presence of Omicron within 48 hours.

Over the first months of testing, about five percent of pooled tests were positive, rising sharply to over 16 percent positivity following the global emergence of Omicron.

This was a striking finding, considering the requirement for incoming travelers to provide a negative test before boarding a flight to the US was still in place at the time. It’s not necessarily that pre-departure testing wasn’t working, but many factors can come into play even with these measures in place — travelers may become infected after testing, or it was too early to detect the virus at the time of the test. The CDC has since lifted the pre-departure testing requirement for international travelers, making the program one of the key tools to intercept pathogens as they enter the country.

Photo by Gerrie van der Walt on Unsplash

The program has since continued at the original airports, expanded to more flights, and enrolled tens of thousands of participants. It continues to serve a number of public health goals. Plus, viral samples for novel variants are also securely shared with CDC labs to further study their characteristics.

The program did prove that a traveler-based program could be the early detection system we need — the program detected the first instances of several sublineages of Omicron in the US and North America. It showed what the future could look like if we operationalize wide-scale passive monitoring of biological threats that can inform a national “weather map” of pathogen detection and spread.

The airport program also underscores the importance of public-private partnerships to achieve public health priorities in an ever-changing biosecurity landscape.

We must be mutually engaged in plugging the holes in our existing biosecurity infrastructure. The program’s scalability and adaptability, including rapidly adding locations and expediting sequencing, are key. These are new security features that were born out of the necessity of the COVID pandemic.

So far, while we have focused primarily on COVID testing, each sample collected can also provide critical insights into other circulating pathogens. We could begin to use this platform to monitor common pathogens that we expect to encounter, like seasonal flu, or even those that we do not expect, like monkeypox. Programs like ours can provide critical early detection so that we can understand the threat and launch appropriate responses. With this in mind, we at Concentric are working to expand our capabilities to be able to catch more than just COVID–to be more prepared for what pathogens might come next.

Photo by Keith Chan on Unsplash

Public health surveillance of emerging infectious diseases has traditionally focused on health clinics after the onset of symptoms, but with the Omicron variant of SARS-CoV-2 especially, transmission often occurred before symptoms emerged, or people were fully asymptomatic. This might happen again, and we must be prepared to detect new variants and pathogens early.

Dr. Wegrzyn is a biosecurity expert at Concentric by Ginkgo, the biosecurity and public health arm of Ginkgo Bioworks. You can follow her on Twitter @rwegrzyn.

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