Why Genomic Sequencing Is Important for the Next Stage of the Pandemic

COVID-19 is a shape-shifter. Minor changes in its genetics can allow new COVID-19 variants to sweep through populations and even reinfect people who have recovered. Genomic sequencing has thus far given scientists clues as to how the next phase of the pandemic would unfold.

But additional funding for sequencing was excluded from the $10 billion COVID-19 bill approved by Congress yesterday. The funds will be dedicated to supporting vaccination, treatment, and testing efforts, while surveillance operations that help predict the next variant will have to scale down.

Wastewater surveillance indicates that Omicron BA.2 may drive another COVID-19 surge in coming weeks. Despite the warning signs, state and local governments are doing away with COVID-19 prevention strategies like mask mandates and vaccination requirements in indoor venues.

The U.S was slow to build its COVID-19 sequencing capacity. But sequencing efforts have improved scientists’ understanding of new variants, informed health providers with treatment recommendations, and compelled vaccine manufacturers to test variant-specific vaccine candidates.

“This is our first big emergency where genomics is actually available, and it can be hugely helpful” Dana Crawford, PhD, professor and genetic epidemiologist at Case Western University. “This is our first big display of what genomics could do.”

Since the beginning of the pandemic, the U.S. has sequenced 3.8% of its COVID-19 samples, with wide variation between states. Sequencing experts say that maintaining or expanding genomic surveillance will be key to making sure that new variants don’t catch health officials off guard in the future.

“We have the expertise, we have the technology, but we were not doing genomic surveillance to the level that we should have been doing, or should be doing now,” Crawford said.

How the U.S. Built Its Sequencing Capacity in a Fractured System

Despite being home to the Human Genome Project, the decade-long effort to sequence the entire human genome, sequencing efforts in the U.S. lagged behind at least 30 countries in 2020.

Now, the CDC can now detect variants that account for as little as 0.1% of all COVID-19 cases. The U.S. now ranks 15th in the percentage of cases sequenced compared to other countries globally. By comparison, the United Kingdom has sequenced more than 10% of its COVID-19 cases and some U.S. experts set a benchmark of sequencing at 5%.

“It really is sort of tremendous the amount of growth we were able to see in about a year,” Kelly Wroblewski, MPH, MT(ASCP), director of infectious diseases at the Association of Public Health Laboratories, told Verywell.

To achieve this, CDC recruited the help of private labs and public labs to boost sequencing capacity nationwide.

Public health laboratories are crucial for genomic surveillance for many diseases. Wroblewski said that while these labs had the capacity to sequence COVID-19, space constraints and other limiting factors meant these labs couldn’t perform the testing at high volume. Partnering with academic institutions and sequencing centers allowed the smaller labs to sequence to scale.

Collaborating to effectively collect, store, and share sequencing data has been challenging, according to Crawford. In the largely privatized American health system, key players such as hospitals, academic institutions, diagnostic labs, sequencing centers, and local health departments are often siloed from one another.

“We don’t have one system that we’re working with—it’s hundreds of systems, and they don’t talk to each other,” Crawford said. “We have the technology, we just need to figure out how to link the data together so that we can respond in an even more timely manner at the public health level.”

The CDC in 2020 created SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance (SPHERES). It allows for collaboration between scientists from different laboratories, institutions, and the private sector to share data and analytical approaches.

Making use of that data at a patient level is still limited. Most sequencing happens far away from the doctor’s office and, due to patient privacy laws in the U.S. and the structure of electronic health records systems, providers can’t easily link data from a sequencing lab to a patient’s clinical record.

The U.S. instead relies on other countries, like the U.K. and Denmark, to provide reports on how severe and transmissible certain variants are, said Soren Germer, PhD, head of sequencing and analytics teams at the New York Genome Center.

Having a more integrated health system and investing in personalized genomics medicine might have allowed clinicians to know which variant a patient is infected with. Since some COVID-19 monoclonal antibodies are more effective against some variants than others, this could help clinicians to better prescribe treatments.

“The key to preparing ourselves for the next pandemic will really be to—without having to completely overhaul our healthcare system—figure out ways that we can be better coordinate next time,” Germer said.

Broad Sequencing Gives a Fuller Picture of Circulating Variants

Having enough samples to sequence can be a challenge. Germer said that when case rates are high, hospitals don’t always have the bandwidth to pull samples and send them to sequencing centers. And when case rates are too low, there could be a dearth of samples in general.

Regional biases in surveillance also exist, Wroblewski said. For instance, academic labs in urban centers will sequence samples from their area, meaning rural areas could be under-represented. Besides, with an increased reliance on at-home antigen testing, positive samples are not always reported to labs to be sequenced.

At a national level, testing a small portion of the total positive cases will give scientists a good sense of which variants are circulating at a given time.

“As you zoom into a state or locality, you run the risk of missing some of the finer detail,” Wroblewski said. “On that local level, you have to work harder or find different ways to bring specimens into the laboratory.”

To the CDC, more important than the total number of sequences is the timeliness of processing and analyzing samples after they’re taken, Wroblewski said.

“Focusing on having good geographic representation and good demographic representation in your sequence data, and then focusing on the timeliness of the data, is where the priority should be,” Wroblewski said.

How Sequencing Factors In to the Future of the Pandemic

In his State of the Union address last month, President Joe Biden said the White House will “do everything within our power to be ready” if a new variant emerges, including monitoring for viral mutations.

When COVID-19 becomes endemic, Wroblewski said sequencing will become more routine. While labs will likely sequence fewer samples, she expects that monitoring will still be done at a level high enough to detect any emerging variations in the virus. This could allow scientists to keep an eye on mutations in the COVID-19 virus, while also surveilling other diseases.  

“We will treat [COVID-19] very much like we treat any other community-transmitted pathogen in our surveillance system,” Wroblewski said. “And that’s not to say that it’s less important, it’s just going to have a more appropriate focus on it.”

Germer said that while it’s important to keep monitoring for new variants for now, building sequencing infrastructure for COVID-19 sequencing may not necessarily be the best long-term investment, as there’s no way to predict what the next pandemic will look like. The next pandemic pathogen may demand higher levels of biosafety from scientists, a different testing mechanism, or it may not be genetically variable enough for genetic sequencing to even be particularly useful.

“It’s a logistical challenge because you have to invest in a lot of infrastructure that could easily lay fallow,” Germer said.

Still, if the government cuts off funding now, programs may end and the expert teams behind them may not reassemble when the next health emergency arises, Crawford said.

“It would be more than a shame—it would be detrimental to our public health system—if we were to dismantle the systems that we set up,” Crawford said.

“It’s really a crucial time right now for genomic surveillance for this particular pandemic, let alone future pandemics,” she added. “We really should be taking this time to strengthen our surveillance programs and to plan for not just new variants for the current pandemic that for other pandemics.”