As the U.S. continues to grapple with the pandemic, there are growing concerns about the risks posed by variants of SARS-CoV-2 – the coronavirus that causes COVID-19. Recent data have shown that at least one SARS-CoV-2 variant is more transmissible than the original, and there are questions as to whether any variants could be more deadly. The main way to detect emerging variants is to perform widespread genome sequencing, but the sequencing infrastructure in the U.S. is struggling to keep up with demand. This issue was a major focus of the Centers for Disease Control and Prevention’s (CDC) briefing to the House Appropriations Subcommittee on Labor, Health and Human Services, Education and Related Agencies this week.
Origin of variants and their detection
Viruses replicate by taking advantage of a person’s own cells, and each replication introduces small changes into a virus’ genetic code. Usually, these mistakes either have no impact, or are harmful to the virus. Sometimes, though, these errors give the virus an advantage, like increased ability to infect other people. Besides increased transmissibility, it is possible that variants could also cause more severe disease, evade detection by diagnostic tests, reduce the effectiveness of treatments, escape infection-induced immunity, or render vaccines less effective.
These risks are why it is imperative that public health officials track the emergence of variants around the country, and around the globe. Variants are found by extracting genetic material from patient samples, using sequencing equipment to read the virus’ genetic code, and comparing it with other known samples. When increasing numbers of cases of disease are found to have been caused by a virus with a genetic signature that is only slightly different from that of the known samples, scientists can estimate that they may have found a new variant. For SARS-CoV-2 specifically, there are a few variants that appear to have an advantage and are able to spread much more easily than the original strain. These variants include the UK and South African strains. There are also some early data that a variant discovered in California is more contagious than the original.
Challenges for genome sequencing of viruses in the U.S.
Public health officials use genomic sequencing to monitor for a variety of viruses, but the increased demand during the COVID-19 pandemic has put the U.S.’ sequencing infrastructure under strain. Though the U.S. has over 28 million COVID-19 cases, or about one-fourth of the total number of cases in the world, only about 96,000 samples, or around 0.3 percent, have been sequenced. For U.S. labs, the sequencing process can be costly and time-consuming, taking 48 hours to readout a virus’ genome in the best case scenario, though typical turnaround times stretch up to seven days. The cost of just one virus genome sequence can be anywhere from $80 to $500.
The country’s current genomic sequencing infrastructure has not been prioritized as a public health need and, in the past, sequencing was typically performed only by research universities. In 2014, the CDC started funding public health labs to track foodborne illnesses with genomic sequencing. By 2017 every state had labs which could perform genome sequencing, but obtaining funding is still difficult.
Current efforts and the road ahead
The CDC has been working to form various partnerships to boost the U.S.’ capacity for virus genome sequencing. According to its website, CDC has focused on several activities to increase genomic sequencing capacity, including:
- Leading the National SARS-CoV-2 Strain Surveillance (NS3) system;
- Partnering with commercial diagnostic laboratories;
- Collaborating with universities;
- Supporting state, territorial, local, and tribal health departments; and
- Leading the SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance (SPHERES) consortium.
CDC Director Rochelle Walensky echoed this during Tuesday’s briefing and noted that under her leadership, the agency has scaled from 250 SARS-CoV-2 sequences per week to 14,000 per week. She hopes to scale up enough that the CDC can sequence 25,000 samples per week, which is close to about 5% of positive cases. To do this, the White House announced last week it would provide $200 million to support more genomic sequencing, and the U.S. Congress is considering adding almost $2 billion to that effort in the next economic relief package.
This funding is also intended to sustain the U.S.’ genomic sequencing infrastructure for the future. Senator Tammy Baldwin (D-WI), who introduced the legislation to support further sequencing, said the federal government should establish “the basis of a permanent infrastructure that would allow us not only to do surveillance for COVID-19, to be on the leading edge of discovering new variants, but also…have that capacity for other diseases.” During Tuesday’s briefing, Ranking Member Tom Cole (R-OK) affirmed this idea, saying that the House Appropriations Committee needs to think about establishing long-term funding streams to ensure that infrastructure developed during this crisis can last well in the future.
The COVID-19 pandemic has highlighted gaps in U.S. infrastructure for the genomic sequencing of pathogens, and the importance of tracking virus variants for our public health. While the CDC works with its partners to rapidly scale up sequencing capacity, lawmakers need to consider how to sustain it for future outbreaks. As the Biden Administration and Congress consider scaling and sustainment, we encourage the CSPI community to serve as a resource to federal officials on this topic.
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