FLC | FDA warns that COVID-19 variants may cause false negatives with molecular tests

FDA warns that COVID-19 variants may cause false negatives with molecular tests

January 12, 2021

The U.S. Food and Drug Administration (FDA) on January 8 alerted clinical laboratory staff and health care providers that 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.

The FDA monitors the potential effects of genetic variation in molecular tests that have received Emergency Use Authorization (EUA) and has been doing so on an ongoing basis throughout the pandemic. The FDA’s analysis to date has identified three molecular tests that have received EUAs whose performance could be impacted by SARS-CoV-2 genetic variants:.

* Accula SARS-Cov-2 Test: The FDA’s analysis, including additional information provided by the manufacturer, Mesa Biotech Inc., indicates that the Accula SARS-Cov-2 Test performance may be impacted when a SARS-CoV-2 virus patient sample having a genetic variant at position 28881 (GGG to AAC) is tested. While the impact does not appear to be significant, the FDA is providing this alert to health care providers out of an abundance of caution while we continue to gather additional data and work with the manufacturer.

* TaqPath COVID-19 Combo Kit: The FDA’s analysis, including additional information provided by the manufacturer, Thermo Fisher Scientific, Inc., and multiple reports from clinical laboratories, indicates that one of three targets of the TaqPath COVID-19 Combo Kit (which may also be labeled as the TaqPath COVID-19 Combo Kit Advanced) has significantly reduced sensitivity due to certain mutations, including one of the mutations in the recently identified B.1.1.7 variant (UK VOC-202012/01). Since this test is designed to detect multiple genetic targets, the overall test sensitivity should not be impacted. The pattern of detection when certain mutations are present may help with early identification of new variants in patients to reduce further spread of infection.

* Linea COVID-19 Assay Kit: The FDA’s analysis, including additional information provided by the manufacturer, Applied DNA Sciences, Inc., indicates that one of the two targets of the Linea COVID-19 Assay Kit has significantly reduced sensitivity due to certain mutations, including one of the mutations in the recently identified B.1.1.7 variant. Since this test is designed to detect multiple genetic targets, the overall test sensitivity should not be impacted. The pattern of detection when certain mutations are present may help with early identification of new variants in patients to reduce further spread of infection.

The FDA continues to monitor the effects of different variants on authorized molecular tests for the detection of SARS-CoV-2 and will update clinical laboratory staff and health care providers accordingly.

The FDA is providing recommendations to address possible false negative results for clinical laboratory staff and health care providers who use molecular tests for the detection of SARS-CoV-2:

* 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.