When SARS-CoV-2 first started rapidly spreading just a little over two years ago, the ability to identify and track positive cases within communities became critical to helping gain control of the pandemic. The molecular diagnostics community met this global challenge by developing accurate, reliable PCR solutions for COVID-19 monitoring and detection at lightning speed. As the virus has circulated around the world infecting over 400 million individuals and changed along the way , these tools and technologies have gotten faster, smarter, cheaper, and more accessible to keep up with unexpected variants and unprecedented demands.
During a recent Labroots webinar, Thermo Fisher Scientific’s Vanessa Lacey, PhDƚ, and Jelena Feenstra, PhDƚƚ, recapped highlights from the COVID-19 detection and surveillance journey thus far, offering insight into how existing tools were designed to remain resilient as the fate of this unpredictable virus remains uncertain.
Molecular tests, such as PCR, remain the most reliable method for COVID-19 detection
PCR and other nucleic acid amplification tests work by targeting and amplifying sections of RNA specific to SARS-CoV-2. These tests are highly sensitive, with the PCR method remaining the gold standard for COVID-19 detection. Antigen tests, which work by binding to specific proteins on the surface of the virus, are also widely available in the community but require more of the virus to be present in a sample to trigger a positive result . In fact, the World Health Organization (WHO) recognizes the reduced sensitivity of antigen tests and enhanced reliability of PCR options by differentiating between the two when confirming an infection . A positive PCR test alone constitutes a confirmed case, while an antigen test is only counted if other criteria are met.
As the SARS-CoV-2 virus evolves, Thermo Fisher’s lab-based PCR solutions for detecting COVID-19 remain robust in the face of variants. These tests were designed with mutations in mind and target multiple SARS-CoV-2 genes — if a genetic change causes one target to fail, the other targets can still be successfully detected to deliver an accurate positive result.
With S gene mutations, diagnostic COVID-19 tests can offer insight into key SARS-CoV-2 changes
The 69-70del mutation in the S gene, which codes for the SARS-CoV-2 characteristic spike protein, was found in the Alpha variant of concern and is also present in the Omicron strain. The spike protein plays a key role in COVID-19 infection and is also the cornerstone of vaccine-induced immunity, making changes within this gene of particular interest.
The TaqPath COVID-19 Diagnostic Solution offers a unique advantage in tracking specific variants carrying the 69-70del in the S gene. The test is designed to detect three different regions of the SARS-CoV-2 genome (S-, ORF1ab- and N- genes). Although the 69-70del mutation prevents a signal from being generated for the S gene, the test remains reliable in detecting COVID-19 overall with robust amplification of the Orf1ab and N gene targets.
When laboratories start to see trends in S gene failure, or “dropout,” with COVID-19 positive tests, it can be indicative of variant patterns. After S gene dropout was noted at the start of the Alpha wave, the subsequent return to results identifying all three gene targets was indicative of the pandemic’s shift to the Delta variant. The S gene dropout pattern returned with Omicron, and continued observations of S gene target failures have been a sign of this variant’s dominance. If labs start to notice more positive S gene results, it could indicate a new variant is taking hold. This capability may prove especially useful as cases of the Omicron subvariant BA.2, which lacks the 69-70del mutation, begin to rise around the world.  While S gene target failure may be used as an indicator of the presence of specific variants, the actual variant in the sample must be confirmed with additional testing using genotyping or sequencing approaches.
Genotyping assays provide a quick, accessible option for surveillance of known variants
As COVID-19 cases fluctuate, a strong surveillance system will remain crucial to gaining and maintaining control of the pandemic. PCR solutions designed specifically for surveillance of known variants, such as Thermo Fisher’s TaqMan SARS-CoV-2 Mutation Panel**, can help track the spread of new, known virus strains over time. These assays provide a fast option for mutation analysis using the same PCR equipment as diagnostic tests. Labs have flexibility to build the panel they want for variant detection and can adapt over time as needed. Encouragingly, a recent study showed 100% agreement between genotyping analyses and whole genome sequencing in the ability to identify the Omicron variant within a sample, backing this solution as a reliable option for variant-specific surveillance activities .
To learn more about how Thermo Fisher is working to provide a continuous supply of reliable solutions for the testing and monitoring of COVID-19, watch the Labroots webinar on demand. For additional information on our specific COVID-19 detection and surveillance technologies, please visit our webpage.
ƚ Vanessa Lacey, PhD, Staff Scientist, Molecular Biology, Clinical Applications, Thermo Fisher Scientific
ƚƚ Jelena Feenstra, Sr. Manager of Global Scientific Communications for Genetic Sciences at Thermo Fisher Scientific
*For Emergency Use Authorization (EUA) only. For prescription use only. For in vitro diagnostic use.
**For Research Use Only. Not for use in diagnostic procedures.
- WHO Coronavirus (COVID-19) Dashboard | WHO Coronavirus (COVID-19) Dashboard With Vaccination Data
- Guidance for Antigen Testing for SARS-CoV-2 for Healthcare Providers Testing Individuals in the Community | CDC
- Omicron BA.2 subvariant fuels new global surge of the pandemic – World Socialist Web Site (wsws.org)
- A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron | medRxiv