Genomic sequencing: A vital tool in combatting the pandemic

As variants of the COVID-19 virus emerge, genomic sequencing could help boost the public health response and provide the impetus to create value for future crises.

Since the beginning of the COVID-19 pandemic, genomic sequencing efforts, particularly in the United States, have fallen behind. While the federal government is taking measures at the national level to increase sequencing for COVID-19, it is equally important that states build on recent momentum to establish their own infrastructure to ensure a timely and precise local response to sequencing data.

Sidebar

The United States has sequenced 200,000 cases, whereas the United Kingdom has sequenced 350,000. 1 US states have been consistently under-sequencing, making it harder to take targeted public health action, react to variants, and efficiently contact trace. With the influx of federal funding, states have an opportunity to build a sequencing utility that not only helps address COVID-19, but also builds the sequencing infrastructure for a more effective future public health system. Additionally, states may consider developing a sequencing network across existing diagnostic and sequencing labs to ensure adequate surveillance, building a local database to aggregate data for timely public health action, and convening a corps of experts to interpret sequencing data for local response.

The critical role of sequencing data

Without sequencing data, public health authorities are blind to viral mutations that may reduce the efficacy of current response tools (for example, safety protocols, tests, vaccines, and clinical care) and are unable to take precise public health action. Sequencing is a powerful tool that enables public health authorities to improve precision, efficacy, and efficiency of public health response. This response includes the following initiatives:

Take informed public health actions.

Genomic sequencing of SARS-CoV-2 in a given population can serve as an early warning system to guide the public-health response. The Netherlands sequenced its first positive samples in late February. Based on the analysis, the government introduced strict mitigation measures within weeks (for example, canceling large events, encouraging working from home, and closing schools). 2

Conduct more efficient case investigations.

Sequencing can help trace viral lineage, transmission, and rate of evolution. These insights, provided by data that can range from cases in a given facility to intercontinental transmission, are an important aid to outbreak investigations. In the case of New York City’s initial outbreak in March 2020, once epidemiologists identified the probable date of introduction and the strain, public health leaders were able to estimate how many people in the area were infected. Such information is vital to support effective response. 3

Gauge the real-time effectiveness of the public-health response and adjust accordingly.

New variants, including B.1.1.7 (the “UK variant”) and B.1.351 (the “South Africa variant”) have highlighted the risk that new strains will increase transmissibility or reduce the efficacy of vaccines. This information has enabled a rapid pivot to the development of vaccine boosters effective against variants. 4

The United States, despite being home to a quarter of the world’s cases, has sequenced less than half a percent of its COVID-19 samples (Exhibit). In contrast, the United Kingdom has sequenced 8 percent of its samples, 5 accounting for 45 percent of the world’s sequences. As a result of its large volume of genome sequencing, the United Kingdom was quick to detect and act on a new, more transmissible variant of the virus in December. By contrast, the United States had little to no sequencing data to inform its response.

The United States has sequenced 0.71% of all positive cases.
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Sidebar

A state-wide genomic sequencing infrastructure not only helps address COVID-19 today but is also a tool that enhances public health effectiveness in the long-term (see Sidebar 1, “The four components of sequencing programs”). Sequencing can be used for more efficient source identification of foodborne disease (for example, norovirus, E. coli, Salmonella, and Hepatitis A), ascertaining the origins of ‘outlier’ cases—those with no known connection to other cases—to contain further outbreaks (as was done in the latter phases of the 2014–16 Ebola outbreak in Guinea), 6 and developing diagnostics and vaccines for novel viruses (as was the case with Zika in May of 2015). 7

The role of US states in expanding genomic sequencing

In an effort to catch-up, the American Rescue Plan of 2021 directs $1.75 billion to the Centers for Disease Control and Prevention (CDC) to support genomic sequencing and surveillance initiatives. While bolstering national surveillance is vital, in order for states to take targeted and timely action, the turnaround time from sample collection to sequence must be short and the sequencing data must be easily paired with patient metadata. To do this effectively, local sequencing is imperative.

Substantive funds have been made available to states to establish these sequencing programs. The Coronavirus Response and Relief Supplemental Appropriations Act of 2021 provides an additional $19.1 billion to states to strengthen laboratory testing by expanding the use of SARS-CoV-2 genomic sequencing and molecular epidemiology for state and local surveillance and response. 8

Sidebar

Public health officials have options for how to direct funds. Efforts could include rapid sequencing and analysis of SARS-CoV-2 genomes by contractors and staff within public health laboratories, enhanced workforce or bioinformatics capabilities (including improved access to cloud computing resources), or the establishment or expansion of partnerships with academia and the private sector (see Sidebar 2, “California’s genomic sequencing partnership”). 9

States have several options for establishing a sequencing capability. The right archetype for each state depends on its existing infrastructure and level of coordination.

Matchmaker

State officials can use existing surveillance systems and data to identify the appropriate diagnostic lab partners and connect them with existing sequencing capacity. Since September, the CDC has been providing funding to labs for sequencing, 10 but a missing link remains access to the right samples. As a matchmaker, the state would leverage state surveillance data to ensure appropriate geographic representativeness of sequenced samples and would need to partner with multiple labs to source samples. The states that are best positioned to play this role already have sufficient sequencing capacity and a surveillance system that receives electronic reports from diagnostic laboratories; they also have the administrative capabilities to manage multiple diagnostic lab partners.

Sequencer

Some states have the ability to serve as the end-to-end sequencing provider, from receiving, testing, and storing diagnostic samples to sequencing the relevant positive samples. In these situations, the state serves as both the diagnostic and the sequencing lab. This functionality reduces operational burden and dependence on multiple lab partners for both supply of samples and sequencing capacity. States that already operate diagnostic-testing laboratories with sufficient coverage across communities and sequencing capabilities are a good fit for this role.

Convener of experts

In situations where diagnostic testing and sequencing are highly federated, states can function as a convener of data and experts to use genomic information for public health action. In this situation, a state would need to build a central database or repository that allows for the merging of patient metadata and sequencing data, and recruit experts to analyze genomic data.

How states can get started

Sidebar

States can follow four steps to assess their existing capabilities and select the appropriate archetype. The level of necessary investment in sequencing programs increases with each step.

  1. Start building data infrastructure. Regardless of the archetype, a state must have a data infrastructure to connect sequencing data to patient metadata. States can consider establishing this capability immediately and begin integrating it with other public health reporting streams (for example, surveillance systems and contact tracing).
  2. Identify sequencing gaps. By overlaying genomic sequences to corresponding geographies, states can determine whether they have sufficient sequencing coverage. This lens may also uncover local hotspots where additional sequencing may be needed.
  3. Begin establishing a network. If coverage gaps exist, states should assess whether the bottleneck is caused by a failure to source samples or insufficient sequencing capacity. This evaluation can be conducted by reaching out to laboratories that contribute to GISAID (Global Initiative on Sharing All Influenza Data) 11 or are a part of the CDC’s Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance (SPHERES) program and confirming their sequencing capacity. If sufficient capacity is in place, states will want to play a matchmaker role to connect this capacity to sources of positive samples.
  4. Expand sequencing capabilities. To augment sequencing capabilities, states may need to partner with local, high-throughput diagnostic labs or augment public-health laboratory capabilities with sequencing.

All organizations—public, private, and nonprofit—have a vested interest in surveillance and genomic sequencing. The more samples that are analyzed, the more accurate and valuable the insights from this data. Further, the investments that entities make to build sequencing capabilities can help to address public-health events in the future. Stakeholders may consider the elements needed to enable effective genomic sequencing and then choose a path that makes the most of existing infrastructure and partnerships. Time is of the essence.

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