6 COVID-19 Tests Impacted by Viral Mutations

Test name (link to EUA): Accula SARS-Cov-2 Test 

Manufacturer: Mesa Biotech

FDA’s analysis: Performance may be impacted when a SARS-CoV-2 patient sample having a genetic variant at position 28881 (GGG to AAC) is tested.

Potential impact: While the impact does not appear to be significant, FDA alerted healthcare providers out of an abundance of caution. 

Notes: FDA’s analysis included information provided by the manufacturer.

Recommendations for clinical laboratory staff and healthcare providers using this COVID-19 Test: Be aware of the current instructions for use for the Accula SARS-Cov-2 Test that include the exact variant location, in silico analysis of the primer binding, and observed performance impact when compared with the perfect match target.

Test name (link to EUA): Linea COVID-19 Assay Kit  

Manufacturer: Applied DNA Sciences

FDA’s analysis: One of the two targets of the test has significantly reduced sensitivity due to certain mutations, including one of the mutations in the B.1.1.7 variant (UK VOC-202012/01). 

Potential impact: Because 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. 

Notes: FDA’s analysis included information provided by the manufacturer.

Recommendations for clinical laboratory staff and healthcare providers using this test: Be aware that one positive target and one negative target showing the S-gene drop out (reduced sensitivity with the S-gene target) when using the Linea COVID-19 Assay Kit is consistent with certain mutations, including those in the B.1.1.7 variant. If local or state clinical laboratories have access to quick turnaround whole genome sequencing services, such as those using the EUA-authorized Illumina COVIDSeq Test, these labs should consider further characterizing the specimen with genetic sequencing when this pattern is identified. If such services are not readily available, local or state clinical laboratories should consider reaching out to the Centers for Disease Control and Prevention at [email protected] for additional information.  

Test name (link to EUA): TaqPath COVID-19 Combo Kit (may also be labeled as the TaqPath COVID-19 Combo Kit Advanced) 

Manufacturer: Thermo Fisher Scientific

FDA’s analysis: One of three targets of the test has significantly reduced sensitivity due to certain mutations, including one of the mutations in the B.1.1.7 variant (UK VOC-202012/01). 

Potential impact: 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. 

Notes: FDA’s analysis included information provided by the manufacturer and multiple reports from clinical laboratories.

Recommendations for clinical laboratory staff and healthcare providers using this test: Be aware that two positive targets and one negative target showing the S-gene drop out (reduced sensitivity with the S-gene target) when using the TaqPath COVID-19 Combo Kit is consistent with certain mutations, including those in the B.1.1.7 variant. If local or state clinical laboratories have access to quick turnaround whole genome sequencing services, such as those using the EUA-authorized Illumina COVIDSeq Test, these labs should consider further characterizing the specimen with genetic sequencing when this pattern is identified. If such services are not readily available, local or state clinical laboratories should consider reaching out to the Centers for Disease Control and Prevention at [email protected] for additional information. 

Test names (links to EUAs): Xpert Xpress SARS-CoV-2; Xpert Xpress SARS-CoV-2 DoD; Xpert Omni SARS-CoV-2 

Manufacturer: Cepheid 

FDA’s analysis: While it is generally unexpected that a single point mutation will impact test performance for most SARS-CoV-2 molecular tests, FDA’s analysis indicates that the Cepheid tests are impacted by a single point mutation in the target area of the test. There are reports noting that two independent single point mutations reduce the test’s sensitivity for detecting the N2 target. The E target is still detected when enough virus is present leading to a “presumptive positive” result in the Xpert Xpress SARS-CoV-2 and Xpert Xpress SARS-CoV-2 DoD tests. Detection of the E target without detecting the N2 target will be reported as “positive” in the Xpert Omni SARS-CoV-2.

Potential impact: Because this test is designed to detect multiple genetic targets, and these mutations do not lead to a false negative patient result (instead reporting as “presumptive positive” or “positive” based on detection of the conserved E gene target), the impact on test performance does not appear to be significant. However, FDA is providing this information out of an abundance of caution. The agency's analysis suggests that the impact of a single point mutation on the test performance is associated with the unique chemistry of the Cepheid tests.

Notes: FDA continues to gather additional information and work with the manufacturer to address this issue.

Recommendations for clinical laboratory staff and healthcare providers using this test: Be aware of the current instructions for use for each test, especially the “Possible Results” and “Results and Interpretation” tables, which describe when a result is positive, presumptive positive, negative, and invalid, and how to interpret each result. Specifically, “SARS-CoV-2 Presumptive Positive” results may indicate the presence of SARS-CoV-2 nucleic acids, and repeat testing may be indicated; refer to the authorized instructions for use. Clinical laboratory staff and healthcare providers should contact Cepheid if they have any questions or concerns or suspect an issue with their Cepheid test.