The SARS-CoV-2 virus has mutated over time, resulting in genetic variation in the population of circulating viral strains over the course of the COVID-19 pandemic. Molecular, antigen, and serology tests are affected by viral mutations differently due to the inherent design differences of each test, reported in a U.S. Food & Drug Administration (FDA) release.
The FDA has provided information regarding the impact of viral mutations on COVID-19 tests, recommendations for clinical laboratory staff and healthcare providers, and information about certain tests for which the FDA has identified potential impacts on performance due to SARS-CoV-2 genetic mutations. The FDA will list tests on this page as the FDA's analyses identify tests for which performance may be impacted for known SARS-CoV-2 variants.
A mutation (also referred to as viral mutation or genetic mutation) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is a change in the genetic sequence of the SARS-CoV-2 virus when compared with a reference sequence such as Wuhan-Hu1 (the first genetic sequence identified) or USA-WA1/2020 (the first identified in the United States).
A new variant (virus variant or genetic variant) of SARS-CoV-2 may have one or more mutations that differentiate it from the reference sequences or predominant virus variants already circulating in the population. Variants of SARS-CoV-2 can have different characteristics. For example, some may spread more easily or show signs of resistance to existing treatment options and some may have no impact when compared with previous and currently circulating virus.
The presence of mutations in the SARS-CoV-2 virus in a patient sample can potentially impact test performance. The impact of mutations on a test's performance is influenced by several factors, including the sequence of the variant, the design of the test, and the prevalence of the variant in the population.
The FDA has collaborated with stakeholders to better understand the public health impact of new SARS-CoV-2 variants and their impact on test performance, has been routinely monitoring publicly available databases, and has coordinated efforts to evaluate the impact of new virus variants on tests that have received Emergency Use Authorization (EUA).
On September 23, 2021, the FDA revised the EUAs of certain authorized molecular, antigen, and serological tests to establish additional Conditions of Authorization in response to the continued emergence of new variants of SARS-CoV-2. These conditions have also been included in other EUAs, such that all EUAs previously issued for COVID-19 molecular, antigen, and serology tests include these conditions, and they continue to be included in new EUAs. These additional conditions require test developers to update their authorized labeling and evaluate the impact of SARS-CoV-2 viral mutations on their test's performance, among other things.
Clinical laboratory staff and healthcare providers should be aware that false negative results may occur with any molecular test for the detection of SARS-CoV-2, particularly if a mutation occurs in the part of the virus' genome assessed by that test. Changes in the viral genome can result in changes to viral proteins and, therefore, can also impact the performance of an antigen or serology test.
The FDA recommends clinical laboratory staff and health care providers who use SARS-CoV-2 tests:
- Be aware that genetic variants of SARS-CoV-2 arise regularly, and false negative test results can occur.
- Be aware that molecular 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.
- Be aware of currently circulating SARS-CoV-2 variants since test performance may be impacted by certain variants.
- Consider repeat testing with a different EUA authorized or FDA cleared molecular diagnostic test (with different genetic targets) if COVID-19 is still suspected after receiving a negative test result.
In addition to these general recommendations, the FDA is providing recommendations for the use of specific tests impacted by genetic variation and FDA's analysis to date has identified certain EUA-authorized molecular tests whose performance may be impacted by mutations in the SARS-CoV-2 Omicron variant.
