• Dr. Soumi Eachempati

Can mutations affect the results of Covid-19 tests?

Updated: Aug 15, 2021

New cases of COVID-19 are being reported at record levels across the country over the past week with 1.7 million cases being recorded last week. Moreover, an average of 3,229 deaths per day attributed to COVID-19 has been reported over the last seven days. This figure exceeds the total deaths recorded both 9/11 and Pearl Harbor.

However, the development of new mutations could actually yield an undercounting of COVID-19 cases and deaths.

For the past several weeks, public health officials across the world have been monitoring the new variants of COVID-19. One variant entitled B.1.1.7 was described first in the UK and has received considerable attention as it now accounts for 60% of London and Southeast UK cases. This variant is composed of 23 mutations including eight in the S gene. Additionally, this variant has been found in 45 countries and at least eight states in the US.

Recently, the B.1.1.7 strain has alarmed worldwide health officials for its contagiousness. Some have deemed the variant to be 50% more transmissible than other strains of COVID-19. In the UK, 15% of the contacts of people infected with B.1.1.7 in England went on to test positive themselves, compared with 10% of contacts of those infected with other variants.

To understand how this variant may be underreported, one has to consider how it is detected. First, a COVID-19 test has to be positive in a particular area. Next, health officials in this area need to sample some cases to perform the genetic analysis of the involved strain. Then, these officials can truly capture the rate of this and other variants. The US is thought to measure only 1% of COVID-19 for genetic evaluation, whereas in the UK where the mutation has been thought to be most prevalent, genetic typing of COVID-19 strains includes an estimated 10% of all cases. Therefore, the strain may be less reported in the US simply because it is not being currently sought.

However, another factor may be contributing to the underreporting of this strain. Health officials everywhere have assumed that the variant would allow all standard COVID-19 tests to be normally captured with PCR and antigen tests and that the variant could then be monitored as described above.

Until a sudden FDA release late last week on January 8, 2021 when the FDA revealed that the presence of the B117 variant could influence the final observed result of COVID-19 tests. The regulator explained that many tests designed to detect COVID-19 evaluate a region in the S gene. Unfortunately, the genetic sequence in this region is altered in some variants such as the UK B.1.1.7. If the test is only looking at a limited number of genetic areas such as the S region, then it may not be able to evaluate properly the presence of COVID-19 if the composition of the S sequence in this variant is different. In this case, the typical genetic pattern for COVID-19 may not be “seen” in a COVID-19 test and the test may yield a false negative result for COVID-19. The process where this region is improperly captured and evaluated due to the variant is called “S-gene dropout.”

In the release, the FDA also singled out two accurate tests by stating “the detection pattern that appears with the TaqPath (from Thermo Fisher) and the Linea TM diagnostic tests (from Applied DNA Sciences) could help with early identification of new variants in patients to reduce further spread of infection.” The regulator went on to add that the two companies had products that were not as subject to the S-gene dropout as they were testing multiple areas in the S gene and not just in the area with the B.1.1.17 variant.

(Of note, the LineaTM test has been the preferred testing partner for the CLEARED4 platform since its EUA approval in May 2020 well prior to this recognition for being able to escape S phase dropout. The CLEARED4 team has always been impressed by Linea TM due to its pooled testing capability, excellent testing accuracy, and superb management team.)

The FDA said false-negative results may occur in some instances of viral mutations but it expects the impact of the mutations on COVID-19 testing accuracy to be "low." The regulator did not clarify what “low” meant but even a 5% false-negative rate would be monumental in the scope of missed COVID-19 cases. Since about 10 million COVID-19 tests are done a week in the US (and given a typical 5-10% positivity rate), around 25,000 false-negative tests could result per week from this variant alone. The total number of inaccurate tests could be double this number when considering all the other imperfections and flaws that have been observed with COVID-19 testing thus far.

Failing to monitor B.1.1.7 has other important implications. The B.1.1.7 variant and other future variants may also have characteristics that potentially makes it less susceptible to a COVID-19 vaccine. In this variant, scientists have