The highly contagious new strain of COVID-19 that’s spreading throughout the United Kingdom may now be coursing through the U.S.
The challenge is finding it.
Unlike the UK, America has not yet fully harnessed the power of genomics to quickly detect important changes in the virus that could alter the trajectory of the pandemic ravaging the country.
“We’re working blind,” with insufficient screening to know how prevalent the strain is, said Dr. Charles Chiu of UC San Francisco, whose lab is collaborating with the state’s Department of Public Health to seek the new variant, called B.1.1.7., in viral samples among recent UK travelers in many California counties.
On Friday, Chiu’s lab discovered two new cases of the variant virus from samples collected from members of a Big Bear-area household on Dec. 20. One member of the household had contact with a traveler who returned from the United Kingdom on Dec. 11. The finding follows news of two cases in San Diego and two cases in Denver, all confirmed on Wednesday. As of Saturday, the variant has been reported in 33 other countries.
Because none of the people involved in the U.S. cases reported traveling, experts fear undetected community spread.
Like all viruses, the COVID-19 pathogen makes tiny changes in its genome as it reproduces. Understanding this evolution — and especially which mutations can change its behavior — is essential for estimating the threat of new strains.
The virus’s genetic makeup, stored in a single strand of RNA, determines whether it might suddenly turn resistant to medicine, or whether a vaccine is protective or futile.
But of the more than 19 million COVID-19 cases officially reported in the United States, just 58,500, or 0.3 percent, have been genetically analyzed for variants, according to the latest data from a centralized database.
And most of these analyses are catching long-gone cases. The average lag time between specimen collection and sequence sharing in the U.S. is 96.6 days – compared to 38.5 days in the UK. While more than half of specimens in that country are sequenced within a month, only 14.7% of U.S. specimens are.
It’s no coincidence that the nation’s first case was found in Colorado. Unlike California and most other states, Colorado’s state lab sequences all COVID-19 samples for the UK variant, according to health officials. That lab also sequences any suspect samples sent by commercial labs.
California is sequencing specimens from people who meet at least one of the following criteria: Recent travel to the United Kingdom or Europe; exposure to persons with recent travel to the United Kingdom or Europe; or a diagnostic test with mutations indicating it could be related to the UK strain. These samples are sent to a network of labs — including California Department of Public Health and local public health labs, diagnostic labs, Chan Zuckerberg Biohub, Invitae Corporation, UCSF and Scripps Institute — collectively called “COVIDNet.”
The state’s discovery of the variant is a wakeup call, said Stacia Wyman, a scientist at the Berkeley-based Innovative Genomics Institute, whose team has sequenced the genomes of 700 COVID-19 virus samples from the East Bay.
“I deeply suspect it is in a lot of other places,” she said. With more universal sequencing, “we would have known that.”
Until now, California has largely focused its sequencing efforts on specific incidents, such as outbreaks at nursing homes, correctional facilities, hospitals and other group settings. Whenever there’s a so-called “superspreader” event, academic and public health labs race to inspect the viral genomes to trace the transmission patterns.
This strategy revealed, for instance, that one person infected 52 others at a fraternity party at UC Berkeley last July. Three specific mutations defined that cluster, said Wyman, whose team led the investigation. Her team searched for that pattern across the genetic sequences of many samples – and, to their relief, found no evidence that the virus had jumped into the broader community.
“It was just shut down,” she said. “The whole strain that defined that cluster just disappeared, because the university had a really good response to it.”
The two San Diego cases were discovered because of that county’s close relationship with Scripps Research, which has a renowned genome sequencing program. The initial illness was detected during UCSD’s mandatory testing program, and in only 17 hours, Scripps had an answer.
It’s unclear how and where this troubling new variant emerged.
While this virus is typically quite stable, accumulating just one or two mutations a month, there have been several notable changes during the course of the pandemic, according to the World Health Organization.
One of the first variants, a mutation called D614G that boosts infectivity and transmission, appeared in China last winter; by June, this was the dominant form of the virus. Another new strain, which potentially decreases immune protection, was spotted in Denmark in August; fortunately, it does not appear to have spread widely.
The troubling new UK variant has 23 distinct differences compared with what’s currently circulating. One of these changes seems to make it more easily transmissible. While this virus is not more deadly than the existing strain, it could be more difficult to contain.
Another variant, announced by South Africa on Dec. 18, seems to also increase transmissibility and has since spread from two provinces to four other nations.
A powerful computer browser at UC Santa Cruz is helping scientists compare hundreds of viral sequences at once, revealing where these new mutations are located and how common they are. This so-called SARS-CoV-2 Genome Browser also shows which parts of the genome are being studied by various teams, and provides information about the mutations. Based on computer code written by postdoc scholar Yatish Turakhia, the browser is far faster than existing tools.
“We absolutely need to increase our surveillance of what the virus is doing and how it is being transmitted,” said David Haussler, professor of biomolecular engineering at UCSC, who leads the effort. “We must keep track of how the virus is taking advantage of us.”
California’s two biggest sequencing centers are San Francisco’s Chan Zuckerberg Biohub, which has sequenced and published 2,817 COVID-19 virus genomes, and the Anderson Lab at Scripps Research, based in La Jolla, which has sequenced and published 2,374 genomes.
A federal infrastructure of “sequencing centers” would create more consistent, representative and thoughtful analyses, said IGI’s Wyman. “Right now, each state sort of does its own thing.”
Here’s the challenge: Sequencing is expensive. It requires manpower. It takes time. And it diverts attention away from more pressing public health needs.
Unlike the UK, whose national strategy of so-called “genomic surveillance” is managed by a handful of big labs, the U.S. effort falls on the weary shoulders of many state and local health departments, which are already stressed by the pandemic. There’s no federal funding for a coordinated and real-time effort. And because our healthcare system is fragmented, there’s no single pipeline that would deliver all positive specimens for sequencing.
There’s a new federal initiative called SPHERES (Sequencing for Public Health Emergency Response, Epidemiology and Surveillance), but it mostly serves as a central repository of data. It doesn’t pay for the actual lab work.
“We can’t even do enough diagnostic testing. So how would you have the resources that are required for sequencing?” said Dr. Omai Garner, associate director of clinical microbiology for the UCLA Health System. “It’s prohibitively expensive and very, very challenging, technically.”
With the crush of current cases, it’s understandable that the nation is focused on testing, vaccinations and reducing the burden on hospitals, experts agreed.
But the arrival of the UK strain warns us of what more could come, they said. Even after everyone is vaccinated, the nation must be vigilant for the surprise emergence of dangerous new strains.
“The idea is to identify local outbreaks from these novel variants before they have a chance to spread, so they are contained,” said Chiu.
“A really robust surveillance system will help to not only control the pandemic now,” he said, “but also in the future.”
How COVID-19 “whole genome sequencing” is done:
- Scientists take infected cells and treat them with chemicals that break them open, releasing the viral RNA. The RNA is then purified.
- RNA is cut into short fragments of known length, using enzymes.
- Scientists make many copies of each RNA fragment using a process called polymerase chainreaction (PCR). The pool of fragments generated in a PCR machine is called a “RNA library.”
- The RNA library is loaded onto a sequencer. The combination of nucleotides (A, U, C, and G) making up each individual fragment of RNA is determined, and each result is called a “RNA read.”
- The sequencer produces millions of RNA reads and specialized computer programs are used to put them together in the correct order, like pieces of a jigsaw puzzle.
- When completed, the genome sequence containing millions of nucleotides — including any surprising changes in the usual sequence, called mutations — is ready for further analysis.
