Larger-scale genome sequencing needed to bolster early warning
The COVID-19 crisis has made clear that the United States and most other countries need to significantly improve their disease detection capabilities. This pressing need—and a glimpse at part of the solution—was driven home by last week’s news of a mutation of SARS-CoV-2 that was discovered in southeastern England and has spread rapidly over the past few weeks, leading to a surge of cases in the United Kingdom. On Tuesday, December 29, a case was identified in the U.S. in Colorado.
The strain, called B.1.1.7, appears to have significantly higher transmissibility than others. As a result, on December 19, the countries of the U.K. announced stricter measures to contain the mutation, including movement restrictions between more and less heavily affected areas. U.K. residents have also been banned from travelling to the Netherlands, Belgium, Italy and other European Union members to try and slow or stop the spread.
The mutation was found in the U.K. and these measures were made possible because of the country’s efforts to sequence samples of the virus. Its Covid-19 Genomics Consortium (Cog-U.K.) is responsible for collecting and making available about half of the world’s genetic sequences of SARS-CoV-2.
In contrast, the United States has less insight into the extent to which the strain has spread domestically because sequencing efforts are more limited. Out of the 17 million U.S. coronavirus cases, only 51,000 virus samples have been collected and sequenced. The mutation has only now been confirmed in the United States despite likely already being in circulation.
This mutation is reminiscent of another SARS-CoV-2 strain, 614G, that was recognized in eastern China and then spread throughout Europe and New York City. It eventually became the dominant strain of SARS-CoV-2 and may have been what made the virus so difficult to stop.
Today’s genome sequencing technology, which is being applied more broadly in the U.K. than in much of the world, is an important tool for early detection of biological threats, including mutations that ease a pathogen’s spread. Such early detection is a critical step toward stopping that threat through various interventions, including behavioral shifts, policy responses and rapid development of medical countermeasures such as vaccines and antivirals.
The specific reason for why U.S. sequencing coverage is so much spottier than the U.K.’s is not clear. Similar to the U.K., there is a government effort to coordinate a large-scale sequencing effort to have a better understanding of SARS-CoV-2 mutations. But to date, there is a massive difference in the number of viruses sequenced in comparison to the total cases. In the United States, .3% of cases have been sequenced. In the United Kingdom, it is 5-10%. Overall the United States is ranked 43rd in the world in terms of percentage of SARS-CoV-2 cases sequenced
The CDC in November launched the National SARS-CoV-2 Strain Surveillance program to track changes in the virus. It is a necessary additional effort and worth watching. But in the longer term, genome sequencing needs to be a more integral part of the U.S. disease early warning toolkit.
And the potential is significant. Given that the cost of sequencing is continuing to decrease exponentially and has been doing so for decades now, sequencing has the potential to be an affordable mainstay of pandemic early detection and warning. In addition, more advanced metagenomic sequencing is necessary as part of an early warning and detection system that maintains flexibility. Metagenomic sequencing is target agnostic and can sift through multiple genome sequences in a sample to identify threats. This type of sequencing can be part of a system to spot and flag the presence of pathogens of all types, not just ones being actively monitored.
With an early warning and detection system where sequencing technologies serve as a backbone, the U.S. can be prepared to respond quickly to new variants of SARS-CoV-2 and other biothreats, especially bioweapons, which countries might today view as being more attractive, given the U.S. presumed vulnerability as a result of the deadly, disruptive effects SARS-CoV-2. This type of system would help protect the U.S. from the full range of biothreats and is necessary as SARS-CoV-2 continues to mutate.
William “Bill” Beaver is a Fellow at the Council on Strategic Risks (CSR), and former analyst supporting the U.S. Defense Innovation Board and the Defense Science Board.
My 2 cents on this point“The specific reason for why U.S. sequencing coverage is so much spottier than the U.K.’s is not clear.” Since the advent of next gen sequencing almost 2 decades ago, many USG agencies including the DOD have invested heavily in building sequencing capabilities both in CONUS And OCONUS locations. Yet, we were/have been late in putting these infrastructures to full use in this pandemic. There is also the question of the color of $$: public health vs defense funds – what can we use for a disease like SARS COV2. At least This was a discussion early on in the pandemic. Besides, there is no national network to coordinate the sequencing surveillance effort such as the UK CoG consortium. Although CDC has formed the SPHERES consortium, how it is coordinating with various testing sites across the country for collecting and sequencing samples (and releasing sequences) that are positive for COVID is not clear. The next big gaping hole is this: the primary means by which the new variant was discovered was by the drop out rates of one of the PCR assays. If only we have access to all the PCR assay signature sequences (primer, probe and amplicon sequences) of all commercial EUA authorized assays we can perhaps monitor assay failures in silico using whole genome sequences in real time. This will allow flagging potential variants before they become full blown catastrophe.
Thanks so much for your comment, Shanmuga. Great addendum to the section you mentioned and useful additional information/idea. The comment already sparked some conversation at CSR. Looking forward to any other opportunities to be in touch/exchange ideas.