Feature

U.K. variant spreading in the U.S. as COVID mutations raise stakes


 

The U.K.’s B117 variant is circulating in at least 24 states, according to new data from the Centers for Disease Control and Prevention COVID-19 variant surveillance. The CDC projects that the U.K. variant will become the dominant strain in the United States by March.

From any vantage point, the United Kingdom appears to be in the crosshairs of COVID-19: Weeks after a new, highly contagious variant emerged that fueled a surge in cases and fresh lockdowns, the United Kingdom was revealed to have the world’s highest coronavirus death rate.

But the United Kingdom also has a not-so-secret weapon of its own: A genomic sequencing program widely believed to be the most coordinated and advanced any nation has forged. In the vise grip of the virus, the Brits have gleaned key insights into the behavior and consequences of SARS-CoV-2.

But B117 is also notable for what it is missing: In this case, producing a negative result on certain polymerase chain reaction (PCR) tests in the spike protein, or S-gene.

One of the S-gene mutations specific to the variant deletes two amino acids, causing that portion of the PCR test to show up negative. The coincidental finding known as an S-gene target failure has become an integral proxy to help track where and when the variant is spreading in the United Kingdom, where about 5% of samples from COVID-19–infected patients are sequenced, said Sharon Peacock, PhD, executive director and chair of the COVID-19 Genomics U.K. Consortium.

That same tactic could prove valuable to clinicians similarly overwhelmed with cases and deaths but lacking high-level sequencing information on the virus, Dr. Peacock said in an interview. A British report released Friday stated that there is a “realistic possibility” that the variant has a higher death rate than other cases of SARS-CoV-2.

“In this particular variant, a deletion in the genome leads to one part of the diagnostic test failing,” Dr. Peacock explained. “Several targets are positive, but this is negative. In the U.K., this has been used as a surrogate marker.”

Targeting an invisible adversary

B117 is not the only variant that produces this result, Dr. Peacock cautioned, “but in screening for it, you can have this in mind.”

“Since the U.K. is sequencing about 5% of the cases they detect, this gives them really important clues about what’s happening there,” said Anderson Brito, PhD, a virologist and postdoctoral researcher at Yale University, New Haven, Conn., where investigators are creating custom PCR tests to detect the B117 variant.

Dr. Brito, who lived in the United Kingdom for 4 years while studying for his doctorate at Imperial College London, said a “major advantage” is the more unified process to collect and sequence samples. Crucial information – including the date and place of collection – comes with each sample, which fuels not only sequencing, but an epidemiologic perspective.

“They’re not in the dark at all,” Dr. Brito said in an interview. “I think no other country in the world knows better which virus lineages are circulating.”

The CDC launched the SPHERES consortium in May 2020 to coordinate the sequencing of SARS-CoV-2 genomes across the United States.

But American genomic efforts are “not as centralized,” said Dr. Brito, whose lab detected the first two cases of the U.K. variant in Connecticut on Jan. 6. “We struggle to get samples, because they’re decentralized to a level where there’s little coordination between hospitals and research centers. They’re not as connected as in the U.K. If we just get a sample and it has no date of collection and no origin information, for example, it’s basically useless.”

Global genomic collaborations include GISAID, an international database where researchers share new genomes from various coronaviruses. As of mid-January, the United States had submitted about 68,000 sequences to GISAID, adding about 3,000 new samples every week and expecting even more from commercial labs in coming days, according to the CDC.

“The U.K. is definitely much more on top of looking for variants as they pop up,” said Gigi Gronvall, PhD, an immunologist and senior scholar at Johns Hopkins Center for Health Security in Baltimore. “The U.S. has now turned that up.”

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