“You might find yourself in a situation where you were unlucky with where you chose to target your test, and something came up there that then made your test less effective,” said Nathan Grubaugh, virologist at Yale University.
The virus’s signature spike protein gene, known as the S gene, has been particularly prone to the mutation, and tests that target this gene may miss some variants. For example, Thermo Fisher’s TaqPath test fails to detect the mutated S gene of the B.1.1.7 variant, which was first identified in Britain and is now spreading rapidly in the United States.
But the test does not rely solely on the S gene; it has three targets and can still return accurate results by detecting two other segments of the coronavirus genome.
According to calculations by Rachel West, a postdoctoral associate at the Johns Hopkins Center for Health Security, only 1.3% of molecular tests rely solely on a target of the S gene. The rest target more stable regions of the genome, which are less likely to mutate, or have multiple target sequences, making them less vulnerable to failure. “It’s very unlikely that you will get mutations in all of them,” said Dr Lillis.
The FDA has listed four different molecular tests “whose performance could be affected” by the variants, but notes that the tests should still work. Three of the tests have multiple targets; a fourth may be slightly less sensitive when the virus has a particular mutation and is present at very low levels. (The four tests are the TaqPath Covid-19 Combo Kit, the Linea Covid-19 Assay Kit, the Xpert Xpress and Xpert Omni SARS-CoV-2, and the Accula SARS-CoV-2 test.)
“We don’t think these four tests are significantly affected,” said Dr. Tim Stenzel, who heads the FDA’s office of In Vitro Diagnostics and Radiologic Health. “It is more out of prudence and transparency that we made this information public.”
Antigen tests are less sensitive than molecular tests, but they are generally cheaper and faster, and they are widely deployed in coronavirus testing programs. These tests detect specific proteins outside of the virus. Certain genetic mutations could modify the structure of these proteins, allowing them to escape detection.