Three new variants in the constantly-evolving SARS-CoV-2 coronavirus have become a cause for concern among health officials worldwide. Although probably not more lethal than existing strains, higher transmissibility rates have stressed public health systems in the United Kingdom, South Africa and Brazil. Three of the authorized SARS-CoV-2 assays have been impacted by the new variants. Though these tests are still effective, their authorizations may require new workflows. The new variants of concern highlight the challenges testing labs face. New variants are inevitable, with unknown impacts on test effectiveness. Labs must have responsive systems that ensure they always use the latest assays, as well as meeting new workflows and reporting requirements.
What SARS-CoV-2 Variants Concern Health Officials?
As of early February 2021, three new variants of the SARS-CoV-2 coronavirus have public health officials worried. The biggest risk at the moment comes from a variant designated the B.1.1.7 lineage (also called 20I/501Y.V1). First detected in the United Kingdom in December 2020, the B.1.1.7 lineage has been found in samples collected three months earlier.
This new variant has a much higher transmissibility rate than other variants. As a result, it only took a few months for the B.1.1.7 lineage to become the dominant strain of SARS-CoV-2 in the UK. As of late January, the US Centers for Disease Control and Prevention recorded the presence of B.1.1.7 lineage infections in at least seventy countries. Since late December, 467 cases of COVID-19 in the United States have been attributed to the B.1.1.7 lineage.
In mid-December, South African health officials identified a new variant that was causing a growing share of COVID-19 cases. Designated the B.1.351 lineage (also called 20H/501.V2), this variant has similar mutations to the British variant but emerged independently in October. The B.1.351 lineage has a transmissibility rate similar to the B.1.1.7 lineage. The variant has spread to at least thirty countries and has caused at least one case in the United States.
The P.1 variant first appeared in Manaus, Brazil, last year and appears to have higher transmissibility. Of more concern, this variant’s antigenic profile may result in reinfection or make vaccines less effective. The P.1 lineage has been found in travelers from Brazil in four countries, including three in the United States. But that’s just the beginning. According to Qiagen’s Chief Medical Officer Davide Manissero, “… maybe there are going to be hundreds of related variants in a year’s time”.
How Do Variants Impact Testing?
In early January, the US Food and Drug Administration assessed the impact of these SARS-CoV-2 variants on vaccines and tests with Emergency Use Authorizations. All rtPCR tests identify specific regions of the SARS-CoV-2 genome. If those regions include the mutation, a test may produce a false-negative.
Fortunately, all of the FDA-authorized tests are still effective. Assays that evaluate a single genomic region do not test the mutated regions. The same is true of most assays that evaluate multiple genomic regions. However, three FDA-authorized assays are impacted:
- MesaBiotech’s Accula: may be impacted when a SARS-CoV-2 virus patient sample having a genetic variant at position 28881 (GGG to AAC) is tested
- Thermo Fisher’s TaqPath: one of three targets… has significantly reduced sensitivity due to certain mutations.
- Applied DNA’s Linea: one of the two targets… has significantly reduced sensitivity due to certain mutations.
Because these assays evaluate multiple regions, however, the FDA concluded that “the impact does not appear to be significant.” Tests conducted with the TaqPath or Linea assays will return mixed positive and negative responses. This detection pattern, the FDA says, “may help with early identification of new variants in patients to reduce further spread of infection.”
Yet public health officials cannot rely on current rtPCR tests for ongoing variant detection. These tests produce positive results for all variants, significant or otherwise, with the targeted genome characteristics. In addition, targeted molecular tests will not identify other variants of concern with mutations in other regions. A recent study warned against using TaqPath to track B.1.1.7 spread in the United States as “as there are clearly non-B.1.1.7 sequences containing the ∆69/70 that are more common than B.1.1.7”.
Genetic sequencing is the gold-standard approach to virus surveillance. This is the only way to identify each variant and track how the virus changes over time. In the United States, genomic surveillance is ramping up slowly. By January 2021, the CDC was sequencing 760 samples per week. Agreements with commercial, academic and public health labs will increase the sequencing rate to 7,000 per week by late March.
Variants Require Labs to Respond Quickly
These three variants are causing serious concern among public health officials. The nature of exponential growth could lead to a B.1.1.7-driven surge in the United States by April. But these are not the only variants — and they will not be the last. Slow vaccine rollout of vaccines within developed countries, disparities in access to vaccines for developing countries and persistent populations of anti-vaxxers will let the SARS-CoV-2 virus survive and mutate for several more years.
Testing laboratories that support the pandemic efforts must be vigilant. New variants will inevitably emerge that make current assays ineffective.Assays that work today may require different workflows and reporting as suppliers learn more about the current variants’ impacts. Labs will need to be agile and respond quickly to changing conditions. If labs don’t adopt new methods and processes quickly, they could report false negatives that keep COVID-19 circulating in the community.
Flexible Data Management Systems Are Essential
Responsiveness is a key feature of LabLynx, Inc.’s COVIDLiMS, a laboratory information management system optimized for the needs of COVID-19 test labs. Deployable in as little as a week, COVIDLiMS comes pre-populated with assays, workflows and reporting for SARS-CoV-2 testing. LabLynx publishes regular updates to keep customers up-to-date as the FDA issues new and revised EUAs. COVIDLiMS customizability also lets labs make their own modifications to reflect changes to internal processes or local reporting requirements.
- “Emerging SARS-CoV-2 Variants” – US Centers for Disease Control and Prevention
- “SARS-CoV-2 Variants” – US Centers for Disease Control and Prevention
- “US COVID-19 Cases Caused by Variants” – US Centers for Disease Control and Prevention
- “Genomic Surveillance for SARS-CoV-2 Variants” – US Centers for Disease Control and Prevention
- “FDA Issues Alert Regarding SARS-CoV-2 Viral Mutation to Health Care Providers and Clinical Laboratory Staff” – US Food and Drug Administration
- “Genetic Variants of SARS-CoV-2 May Lead to False Negative Results with Molecular Tests for Detection of SARS-CoV-2 – Letter to Clinical Laboratory Staff and Health Care Providers” – US Food and Drug Administration
- “Detection of non-B.1.1.7 Spike ∆69/70 sequences (B.1.375) in the United States” – Virological.org
- “Qiagen warns against using standard tests to track coronavirus variants” – Reuters
- “US plays catch-up on genomic sequencing to track COVID-19 variants” – Financial Times
- “Meet the Press January 31, 2021” – NBC News