Avian Flu Diary: FDA: SARS-CoV-2 Viral Mutations

Credit FDA

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For evidence of COVID's continued evolution we need look no further than the loss of effectiveness of all of the monoclonal antibody treatments developed during the first two years of the pandemic (see FDA Withdraws EUA For Last COVID Monoclonal Antibody: Bebtelovimab) and the reduced effectiveness of our current vaccines against newer variants.

Several antiviral medications (e.g. Paxlovid, Veklury and Lagevrio) still remain viable treatment options, along with steroids and supportive therapy, but newer, updated therapeutics are badly needed.

This continual evolution can also affect the reliability of both laboratory and home rapid testing kits. While most of the existing tests are still believed effective, today the FDA has released a lengthy review of the evolution of the virus, and has listed a small number of tests that may be adversely impacted.

Due to its length, I've only posted some excerpts, so follow the link to read it in its entirety. This, unfortunately, is likely to become a bigger issue over time.

SARS-CoV-2 Viral Mutations: Impact on COVID-19 Tests

The SARS-CoV-2 virus has mutated over time, resulting in genetic variation in the population of circulating viral strains, also called lineages. This genetic variation may impact the virus's properties such as transmission (for example, it may spread more easily) or the severity of symptoms on infected individuals (for example, it may cause more severe disease).

This page provides information about tests authorized by the U.S. Food and Drug Administration (FDA) for the identification and differentiation of specific SARS-CoV-2 mutations and lineages as well as the impact of viral mutations on COVID-19 tests.

Recommendations for clinical laboratory staff and health care providers and information about certain tests for which the FDA has identified potential impacts on performance due to SARS-CoV-2 genetic mutations are also included on this page. The FDA will update this page when significant new information becomes available, including when the FDA's analyses identify tests for which performance may be impacted for known SARS-CoV-2 variants.

For consumer information on COVID-19 testing, visit Coronavirus Disease 2019 Testing Basics.

On this page:

Tests Expected to Have Reduced Performance for the SARS-CoV-2 Omicron Variant and Sub-Variants

Omicron Variant and Sub-Variants: Impact on Molecular Tests

Other Variants: Molecular Tests that May Be Impacted

(SNIP)

Tests Expected to Have Reduced Performance for the SARS-CoV-2 Omicron Variant and Sub-Variants

Luminostics, Inc. Clip COVID Rapid Antigen Test (as of 12/13/2022)

Manufacturer: Luminostics, Inc.

Test Name (Link to EUA): Clip COVID Rapid Antigen Test

The FDA's Analysis: Performance may be impacted when a patient sample containing the SARS-CoV-2 virus with certain viral mutations is tested. The mutations impacting performance include a mutation of the nucleocapsid protein, E136D, associated with the BE.1 and BQ.1/BQ.1.1 omicron variants.
Potential Impact: While the impact does not appear to be significant, the FDA is providing this information out of an abundance of caution.

Notes: The FDA's analysis included information provided by the manufacturer and the NIH RADx program.

Recommendations for Clinical Laboratory Staff and Health Care Providers Using This Test
Be aware of the current instructions for use for the Clip COVID Rapid Antigen Test, especially the "Results and Interpretation" tables, which describe when a result is positive, negative, invalid, and aborted, and how to interpret each result. In addition, please refer to the "Antigen EUA Revisions for Serial (Repeat) Testing" for further information regarding updates to the authorized uses regarding the need for serial (repeat) testing. Clinical laboratory staff and health care providers should contact Luminostics, Inc. if they have any questions or concerns or suspect an issue with their Luminostics test.

(SNIP)

Omicron Variant and Sub-Variants: Impact on Molecular Tests

The 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 and its sub-variants. These tests fall into three categories, as described below: those that are expected to have reduced performance for the SARS-CoV-2 omicron variant and its sub-variants, those that are expected to fail to detect the SARS-CoV-2 omicron variant and its sub-variants, and those that are expected to detect the SARS-CoV-2 omicron variant and its sub-variants with a specific gene drop out detection pattern.

Tests Expected to Have Reduced Performance for the SARS-CoV-2 Omicron Variant and Sub Variants

DxTerity SARS-CoV-2 RT PCR CE Test (as of 12/29/2022)
Test Name (Link to EUA): DxTerity SARS-CoV-2 RT PCR CE Test
Manufacturer: DxTerity Diagnostics, Inc.

The FDA's Analysis: Test performance may be impacted when a patient sample contains certain viral mutations of the SARS-CoV-2 virus. Two of the three targets of the test (N-gene target and E-gene Target) have significantly reduced sensitivity due to certain SARS-CoV-2 Omicron variant mutations, including the N: 28370-28362 deletion and E: A26275G, C26270T mutations associated with the XBB variant, the BA.2.75 variant, and the BN.1 variant.

Potential Impact: Two of the three test targets have been shown to have significantly reduced sensitivity in certain variants. The test has an increased likelihood to produce an indeterminant result when testing positive samples of the XBB variant, BA.2.75 variant and the BN.1 variant.
Notes: The FDA's analysis included information provided by the manufacturer.

Recommendations for Clinical Laboratory Staff and Health Care Providers Using This Test

Be aware of the current instructions for use for the DxTerity SARS-CoV-2 RT PCR CE Test, especially the "Result Interpretation for Patient Samples" tables, which describe when a result is positive, negative, indeterminate, or invalid, and how to interpret each result. Specifically, "SARS-CoV-2 Indeterminate" results may indicate the presence of SARS-CoV-2 nucleic acids and repeat testing may be indicated; refer to the authorized instructions for use. Health care providers should contact DxTerity Diagnostics if they have any questions or concerns or suspect an issue with their DxTerity Diagnostics test.

Tests Expected to Fail to Detect the SARS-CoV-2 Omicron Variant and Sub-Variants

Due to the inability of these tests to detect the SARS-CoV-2 omicron variant and sub-variants, the FDA recommends that tests listed in this section, if any, should not be used until this issue is resolved. Once such an issue is resolved, tests are moved to the "Issue Resolved" section below with information about the resolution.