FDA: Coronavirus Variants May Cause False-Negative Tests

The new SARS-CoV-2 genetic variant originally detected in the U.K. may cause some false negatives on certain molecular tests, the FDA said in an alert to healthcare providers and laboratories on Friday.

Variant B.1.1.7 and other genetic variants may impact the performance of certain diagnostic tests, and the agency emphasized false-negative results can occur if a mutation occurs in a part of the virus’s genome being assessed by the test. Therefore, tests that rely on multiple regions of the genome may be less impacted than those that only rely on a single region, the FDA said.

Because the B.1.1.7 variant is thought to be more transmissible, “early identification of this variant may help reduce spread of infection,” the agency said. Still, it characterized the impact to overall testing accuracy as “low” and cited no episodes of actual false-negative results.

The alert was prompted by so-called in silico simulations that suggested “reduced analytical sensitivity” for certain molecular tests for coronavirus variants.

The agency highlighted three specific tests for which the variant may potentially impact test performance, including reduced sensitivity to certain mutations:

• Accula SARS-CoV-2 Test (Mesa Biotech)
• TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific)
• Linea COVID-19 Assay Kit (Applied DNA Sciences)

However, the FDA noted that the impact on Accula test does not appear to be significant — saying it was issuing the alert “out of an abundance of caution” — and because the latter two target multiple genetic elements, no risk of false-negative results is expected with them.

In fact, there may be a benefit with those two tests: “Importantly, the detection pattern that appears with the TaqPath and Linea diagnostic tests when certain genetic variants are present may help with early identification of new variants in patients to reduce further spread of infection,” the agency said.

FDA encouraged clinicians to consider any negative results in combination with clinical observations, patient history, and epidemiological information, and to do repeat testing using a test with different genetic targets. The agency added it is working with sponsors whose tests may be impacted to update labeling to reflect potential changes in test performance and “to consider modifications to the test, if needed.”

The FDA said it is continuing to monitor emerging genetic variants to ensure testing accuracy.

“At this time, we believe the data suggests that the currently authorized COVID-19 vaccines may still be effective against this strain,” said FDA Commissioner Stephen Hahn, MD, in a separate statement.