New Information about Variants and Tests

On January 8, the FDA released a warning that certain PCR tests for SARS-CoV-2 available by EUA may have seriously reduced sensitivity for the SARS-CoV-2 Variant of Concern (VOC, also known as 20I/501Y.V1, VOC 202012/01, or B.1.1.7), resulting in false negative test results.  The tests mentioned in this advisory are the Accula SARS-Cov-2 Test by Mesa Biotech, the TaqPath COVID-19 Combo Kit by Thermo Fisher Scientific, and the Linea COVID-19 Assay Kit by Applied DNA Sciences.  How will this development impact testing?

The SARS-CoV-2 virus mutates regularly with new strains emerging once every two weeks.  Mutations occur in the genetic material of the virus, the very material that molecular test methods like PCR use to detect the virus.  Until recently, none of these mutations has been associated with different clinical characteristics, such as more severe disease or increased rate of transmission.  However, a variant of concern (VOC) recently emerged in the UK.  As far as we know, this is still the one and only VOC.  Since this VOC has a much higher rate of infectivity than standard SARS-CoV-2 virus, we can expect it to spread quickly. It will probably soon become the predominant form of the virus in the United States.  

PCR tests look for a match in a region of viral RNA.  The target sequence is like a computer password:  any mistake causes the password to fail, even if the entry is off by only one letter.  Therefore, when a mutation occurs in the target region of a PCR test, the test will be unable to detect the virus.  This is why the tests mentioned in the FDA warning may not detect all forms of the virus.

Most PCR tests look for a match in more than one target sequence of RNA.  Generally, the more targets in a particular test system, the less likely a mutation will impact test results.  But beware: negative results should be evaluated in combination with history and symptoms.  If COVID-19 is still suspected after a negative test, consider repeat testing with a different test—one with different targets.

How do you know which test you received?  Look closely in the fine print of the results—the test used is probably referenced there.  If not, ask. 

Although most commercially available tests will continue to detect the VOC, these tests do not identify whether the virus is the variant or standard form.  They will only identify that a SARS-CoV-2 virus is present.  Furthermore, there is no assurance that a variant will not emerge that evades detection.  

Obviously, this is a situation we will continue to follow closely.