The highly transmissible Covid-19 virus variant that first emerged in the U.K. can partially evade a commonly used coronavirus test. Some health authorities are using that fact to their advantage.
As more-transmissible variants emerge as a concern in the fight against the virus, the vast majority of Covid-19 diagnostic tests haven't been affected. But for a handful, including one from diagnostics giant Thermo Fisher Scientific Inc., a section of the test can't pick up on variants including the U.K. variant that have a specific mutation, the company, laboratories and health officials who have processed its tests said.
Yet the other parts of the tests still work. So if a test comes up positive for Covid-19 but that portion of the test fails, that could indicate that the samples contain the U.K. variant. Some laboratories are exploiting the bug to more quickly find cases that might be caused by the fast-spreading variant.
"It's actually been a benefit for public health to be able to monitor," Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health, said at an online event last week. "There was a silver lining there."
The tests in question are PCR tests: molecular tests that search for specific portions of the virus's genetic code and amplify them. They are often performed in a lab. The large majority of Covid-19 diagnostic tests, including both molecular and rapid-antigen tests, are able to flag known Covid-19 virus variants as a positive test result.
When laboratories flag the mixed test results from those few PCR tests, researchers can use a technique called genome sequencing to determine which variant has been found. Public-health authorities say more-widespread viral sequencing and better genomic surveillance are necessary to track variants circulating around the globe.
Viruses mutate constantly as they replicate and spread. Most changes don't alter their core characteristics, but some can impact their ability to spread or the severity of disease they cause. Recent variants from the U.K., South Africa and Brazil have raised concerns among scientists because they appear to be more transmissible; vaccines and treatments might be less effective against the variant from South Africa, early research suggests.
Scientists say the U.S. doesn't have a clear picture of how widespread Covid-19 variants are in the country. The country's genomic surveillance system is improving but still trails behind that of the U.K. More than 1,500 cases caused by the U.K. variant, called B.1.1.7, have been identified across 42 states. The U.S. Centers for Disease Control and Prevention estimates the fast-moving variant could become the dominant one in the country in March.
Just as the virus's mutations threaten to blunt the effectiveness of vaccines and therapies, they also have the potential to diminish the accuracy of Covid-19 tests. The variant discovered in the U.K., for example, has several mutations on what is known as the spike protein, which can affect the efficacy of tests that search for that part of the virus or viral genome, health authorities say.
Federal officials have said the CDC, the Food and Drug Administration and manufacturers are evaluating how authorized tests hold up against the new variants. The FDA intends to notify healthcare providers and the public if any new information becomes available, an agency spokeswoman said.
The impact on diagnostic testing so far appears to be minimal, in part because most available Covid-19 tests don't search for that part of the virus.
Of 246 FDA-authorized tests that search for the virus's genetic material, 85% don't target the spike gene, according to an analysis by researchers at Johns Hopkins University. Most rapid-antigen tests, which search for pieces of viral protein, hunt for the nucleocapsid protein, not the spike protein.
"Most diagnostic tests will still be fine because they're not looking for the place that mutations have been found," said Gigi Kwik Gronvall, an immunologist and senior scholar at the Johns Hopkins Center for Health Security.
Among tests that do search for the spike gene, many look for other parts of the virus's genome as well, making them more robust. Manufacturers design many molecular tests to look for more than one part of a virus's genome in part to withstand such mutations.
One of the tests, Thermo Fisher's TaqPath Combo Kit, looks for three targets including the spike gene. The part of the test that searches for the spike gene fails to pick up some coronavirus samples, including the B.1.1.7 variant, a phenomenon dubbed the "S-gene dropout" by some health authorities. The other two targets are able to detect the variants.
"You only need two of the three to call it a positive test," Kimberly Hanson, chief of clinical microbiology at ARUP Laboratories in Salt Lake City, said at a media briefing last month. Molecular tests that fail to identify the spike gene but pick up the other pieces of the virus's genetic code might be flagging cases caused by the B.1.1.7 variant, she said.
As of Feb. 8, ARUP Laboratories, a national laboratory affiliated with the University of Utah, has screened more than 77,000 Thermo Fisher test results and found roughly 400 instances of the S-gene dropout. The company had performed whole-genome sequencing on 150 of them and found four cases of the B.1.1.7 variant from states including Utah.
An S-gene dropout isn't always due to the U.K. variant; it could result from another variant with related mutations, infectious disease experts say. Whole-genome sequencing is required to make the distinction.
Still, laboratories and health officials have found cases caused by the variant through the S-gene dropout in states including Colorado, Minnesota and Washington. Researchers in the U.K. also started following S-gene dropout rates to track the spread of B.1.1.7 when it was first detected there last fall.
Thermo Fisher first received reports of such cases from customers in the U.K. about the failure in September and October and started receiving reports from the U.S. in December, said Mark Stevenson, the company's chief operating officer and executive vice president. Thermo Fisher has developed a software update that can help laboratories flag dropouts more easily, he said, as well as a new test that can identify specific mutations related to key variants.
Helix OpCo LLC, a genomic-sequencing company, makes a Covid-19 test that also exhibits S-gene dropout. That enabled the company "to have an earlier detection [of the B.1.1.7 variant] than if we were randomly sampling throughout the country," said James Lu, co-founder and president at Helix.
The S-gene dropout can also sometimes be a good proxy for where and how quickly the variant is spreading, Dr. Lu said. Helix, which recently partnered with the CDC to scale-up Covid-19 surveillance in the U.S., is following the rate at which tests produce the dropout to help track the variant in California and Florida, along with genomic sequencing.
Dr. Lu and other health authorities say exploiting the S-gene dropout isn't enough to track all of the viral variants circulating in the U.S., and they are pushing for a broader genomic-surveillance system. The Biden administration on Wednesday said the CDC will invest nearly $200 million to scale up genetic sequencing of the virus to track emerging variants.
"The focus needs to be larger than the U.K. variant," said Frederick Nolte, Covid-19 response steering committee chairman at the Association for Molecular Pathology.
https://www.marketscreener.com/quote/stock/THERMO-FISHER-SCIENTIFIC-14623/news/Thermo-Fisher-Scientific-How-Some-Covid-19-Tests-Can-Flag-a-Key-Variant-32505411/
