Coronavirus Tests Will Never Be Variant-Proof – The Atlantic

Most of the coronavirus tests deployed in the United States detect specific stretches of RNA, the genetic material of the viruss genome, usually chosen because theyre unique to SARS-CoV-2 (or at least the virus family its in). When the tests fail, its because theyre picky. These molecular tests search the genomic manuscript with about as much precision as the Ctrl+F function on a computer, which means that even single-letter typosthat is, simple RNA mutationscan discombobulate them.

According to the FDA, almost none of these tests is actually pinging back variant-related false negatives, with perhaps the exception of the Accula, made by Mesa Biotech. A document from the company says the test can occasionally be stumped when it encounters mutations in a gene called N (which produces the nucleocapsid protein), leading it to mistakenly say that no virus is present at all. But thats an extreme case. Three other molecular tests identified by the FDA as being affected by mutations are still able to at least partially register the pathogen. (At least two more recently identified by researchers may soon join the list of tests whose detective powers are weakened, but not obliterated, by variants.)

Read: Fewer Americans are getting COVID-19 tests

One test on the FDAs list, Thermo Fisher Scientifics TaqPath, targets a segment of the S coronavirus gene (which encodes the spike protein). A snippet of that segment is missing from several variants of concernincluding the very contagious Alpha (B.1.1.7), the dominant form of the coronavirus in the U.S.rendering S effectively invisible to the TaqPath. But most molecular tests, including the TaqPath, have a de facto insurance policy: They generally scan the genome for multiple RNA segments at a timetwo, three, sometimes moremaking it nearly impossible for the virus to elude the tests scrutiny entirely. The TaqPath, for instance, detects two additional gene segments outside of S, both of which are intact in Alpha, and will still spit out a positive result.

A slightly different set of issues is now playing out with antigen testsa type of rapid test that can usually be done outside a labwhich detect coronavirus proteins. While molecular tests essentially scan genomes letter by letter for precise spelling, tests that search for proteins work more like a reader skimming words for overall meaning. Typos might slip by unnoticed, making antigen tests tougher to flummox with minor mutations. However, while molecular tests typically have multiple targets, antigen tests tend to have only one, usually the nucleocapsid protein, which makes them more brittle, says Alex Greninger, the assistant director of the clinical-virology laboratories at the University of Washington Medical Center.

In a recent paper, not yet published in a scientific journal, Greninger and his colleagues found that a common nucleocapsid-hunting antigen test called the Sofia, made by Quidel, might not recognize a very small fraction of coronavirus variants, incorrectly marking infected samples as virus-free. Greninger told me that the test-confounding mutation is present in less than 0.5 percent of SARS-CoV-2 genomes cataloged to date, so the test itself is fine for now. But the mistake its making isnt necessarily an anomaly. Another recent study, also not yet peer-reviewed, claims a similar issue with a test called the PanBio, made by Abbott. The PanBio isnt available in the U.S., but its similar to another test made by Abbott, the BinaxNOW, that has been authorized by the FDA.

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Coronavirus Tests Will Never Be Variant-Proof - The Atlantic