COVID-19 variants may lead to false negative tests, FDA says

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Genetic variants of SARS-CoV-2, the virus that causes the novel coronavirus (COVID-19), may lead to false negative test results with molecular tests, according to a letter to clinical laboratory staff and healthcare providers released Friday by the U.S. Food and Drug Administration (FDA).

The SARS-CoV-2 virus can mutate over time, resulting in genetic variation in the population of circulating viral strains, the agency said in its statement. False negative results may occur with any molecular test for the detection of SARS-CoV-2 if a mutation occurs in the part of the virus’ genome assessed by that test.

In its letter, the FDA identified three molecular tests that have received Emergency Use Authorization whose performance could be impacted by SARS-CoV-2 genetic variants, the Accula SARS-Cov-2 Test, the TaqPath COVID-19 Combo Kit, and the Linea COVID-19 Assay Kit. The presence of SARS-CoV-2 genetic variants in a patient sample can potentially change the performance of the SARS-CoV-2 test. Molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to the effects of genetic variation than tests designed to detect a single genetic target, according to the FDA.

The FDA said clinical laboratory staff and healthcare providers must remember that no test is perfect, and there is risk of false negative results with all laboratory tests, including molecular tests. Laboratories should expect some false results to occur even when very accurate SARS-CoV-2 tests are used. The prevalence of genetic variants may vary in any population and may lead to more false negative results than otherwise expected, the agency said.

The FDA recommends clinical laboratory staff and health care providers who use molecular tests for the detection of SARS-CoV-2 to:

  • Be aware that genetic variants of SARS-CoV-2 arise regularly, and false negative test results can occur.
  • Be aware that tests that use multiple genetic targets to determine a final result are less likely to be impacted by increased prevalence of genetic variants.
  • Consider negative results in combination with clinical observations, patient history, and epidemiological information.
  • Consider repeat testing with a different test, with different genetic targets, if COVID-19 is still suspected after receiving a negative test result.

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