The recently reported Omicron variant of SARS-CoV-2 has a 69-70del mutation in the S-gene (which codes for the spike protein). This implies that the S-gene is not detected on PCR tests. The World Health Organization (WHO) in a statement on November 26, 2021, stated that this S-gene “dropout” or S-gene target failure (SGTF) could be used as a biomarker to detect the variant at faster rates than previous variants pending sequencing for confirmation.
There are several problems with using SGTF as a biomarker.
- Although the Delta and Omicron variants are the dominant SARS-CoV-2 variants as of this writing, previous variants like the Alpha variant also had the 69-70del mutation that resulted in SGTF.
- Factors like poor sample collection or test kit variability could also result in what could be deemed an SGTF.
- Although next-generation sequencing (NGS) is a powerful diagnostic tool, labs and institutions could waste money and time sequencing samples by depending solely on SGTF as a biomarker for Omicron.
- A newly described “stealth” sub-strain of the Omicron variant does not contain the 69-70 deletion that leads to SGTF. Furthermore, an N-gene target failure (NGTF) was detected on two EUA assays in late November. Thus, the FDA has said that the use of SGTF and NGTF to definitively distinguish Omicron is “not ideal”.
“The advantage of using Seegene’s FDA EUA AllplexTM 2019-nCoV (SARS-CoV-2) assay, and NovaplexTM Variants assay (Research Use Only-RUO) is that we can screen out what we already know. By isolating the results that don’t align with the already-described Alpha, Beta, and Delta variants, we are able to pinpoint the exact samples that would be sequenced for the Omicron variant. Doing this helps us to avoid assay competition on the same sequencing chip and saves us a considerable amount of time and money,” says Aron Banks, CEO of CardioPath Laboratories. CardioPath Laboratories is a US-based comprehensive laboratory that performs COVID-19 testing with a high-throughput capacity of 1,000 patient samples per day. CardioPath is registered as a CLIA (Clinical Laboratory Improvement Amendments) and CAP-accredited high-complexity lab. They routinely run testing LDT validated protocols using Seegene’s AllplexTM 2019-nCoV (SARS-CoV-2) Assay (EUA), NovaplexTM Respiratory Syndromic, Gastrointestinal and Urinary Tract Infection Panels (all currently available for Research Use Only in the U.S.).
Using an algorithm that screened for already-described variants and then sequenced positive samples that were unspecific for a variant, CardioPath was able to detect the Omicron variant and get results within 30 hours instead of the typical 72-hour timeframe.
“A delay in detecting and understanding new variants means we’re not able to pivot fast enough. This is especially important to public health and hospital systems because lives are impacted by the early detection (or lack thereof) of SARS-CoV-2 variants,” according to Banks.
Having mutation-specific assays for variants of concern means in the future, labs will be able to sift through patient samples quickly, eliminate those that are positive for another variant and encourage quick movement on detecting a new variant. This could potentially shave weeks off detecting a new variant of concern.
Banks added, “What I find extremely exciting is the fact that FDA recently opened up applications for genotyping-based PCR assays. This is a huge step forward from the straight positive/negative assays to assays that detect both the presence of the virus as well as the strain. This will accelerate our sequencing workflows and shorten time to results for better patient care and overall surveillance.”
Seegene recently confirmed that the performance or quality of the Seegene EUA Allplex™ 2019-nCoV Assay for SARS-CoV-2 is not impacted by either the Omicron or Delta variants. Seegene carried out an in-silico analysis to study the Omicron variant, indicating that their assay can amplify and detect the SARS-CoV-2 Omicron sequence.
Seegene also recently introduced a new PCR test, NovaplexTM Variants VII Assay, that is designed to detect mutations consistent with the Omicron Variant and its stealth version in a single tube. This assay is currently for RUO in the U.S. and not for use in diagnostic procedures.