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Rare Coronavirus Mutation Can Complicate COVID-19 Testing, St. Louis Researchers Report

A nurse swabs a patient's nose last year at a the Samuel Rodgers Health Clinic drive-thru COVID-19 test site in Kansas City, Missouri.
Julie Denesha
A nurse swabs a patient's nose last year at a the Samuel Rodgers Health Clinic drive-thru COVID-19 test site in Kansas City, Missouri.

A rare coronavirus mutation can affect COVID-19 testing reliability, new research from Washington University has found.

Identified in a handful of St. Louis patients last year, the mutation may make it harder for certain commercial tests to detect an infection. But researchers emphasize that the vast majority of COVID-19 tests target multiple regions of the coronavirus genome, increasing the chances of spotting the virus if it’s present.

The coronavirus has mutated into a constellation of new versions in recent months, including more contagious variants that can dodge infection-fighting antibodies.

The variant first identified in India, for instance, has a slew of mutations that can boost transmission rates — and may be partially responsible for a massive surge in cases this spring.

Federal officials are warning these mutations also could affect the performance of COVID-19 tests and have recommended companies routinely monitor for any that could compromise test performance.

Current tests use short segments of DNA known as primers, said David Wang, who studies emerging viral pathogens at Washington University.

These primers are designed to match specific regions of the coronavirus’ genetic material. If the virus is present, the primer binds to it and copies it over and over again — creating millions of duplicates hitched to special fluorescent dye.

“If you have a mutation in the region where the test is trying to match, the primers can no longer bind or they don’t bind as well,” said Wang, professor of molecular microbiology at Washington University and study co-author. “This can lead to what we call false negatives, where a sample is actually positive for the virus, but the test gives a negative result.”

A backup system

A series of puzzling COVID-19 test results in St. Louis last year got Wang and his colleagues wondering whether certain mutations might affect test reliability.

Out of thousands of samples, a small number showed inconclusive results. As it turned out, each sample had a version of the coronavirus with the same genetic mutation.

“Since this was the only mutation in the entire gene, we can pretty confidently say this is the reason that this test performed this way,” said Stephen Tahan, who helped lead the study as a research technician at Washington University. “It was because of this mutation, specifically.”

Tahan scoured online databases and found the mutation has surfaced on at least three other continents — Africa, Asia and Europe — but it remains rare, accounting for just 21 samples out of more than 284,000.

Unlike other variants, this version of the coronavirus does not appear to be more contagious, perhaps explaining why it hasn’t become more common globally.

The results support those of previous studies, showing that mutations in the coronavirus genome can affect how well certain commercial COVID-19 tests work.

Still, the majority of tests target two or more regions of the coronavirus genome, functioning as built-in reinforcement as the virus continues to change. In other words, even if one of the regions has a mutation, the other can serve as a backup.

“It’s like combination drug therapy,” Wang said. “A bug can have resistance to one drug, but the odds of being resistant to both drugs at the same time is extraordinarily low. It’s the same principle."

Follow Shahla on Twitter: @shahlafarzan

Shahla Farzan is a PhD ecologist and science podcast editor at American Public Media. She was previously a reporter at St. Louis Public Radio.