Tracking New COVID-19 Variants With a PCR Quirk: Spike Gene Target Failure

Weekly SARS-CoV-2 lineage proportions from genomic sequencing (colors) and the share of pharmacy test results with the spike gene detected (black line, with 95% confidence interval), November 2021–January 2023. CDC.

The idea

Some PCR tests look for three parts of the virus's genome at once. When the Alpha variant appeared in late 2020, a small deletion in its spike (S) gene (Δ69–70) made one widely used test — the TaqPath COVID-19 Combo Kit — fail to detect the S gene while still detecting the others. This pattern is called S-gene target failure (SGTF); its absence is S-gene target presence (SGTP).

Dominant U.S. lineages have tended to alternate between SGTF and SGTP, so the share of each among routine test results gives an early signal of a new variant taking over — alongside genomic sequencing.

In late 2022, while Omicron BA.5-related lineages (SGTF) dominated, an SGTP lineage, XBB.1.5, began spreading rapidly in the Northeast and elsewhere.

The data

• Tests: through CDC's Increasing Community Access to Testing (ICATT) program, specimens from a national pharmacy chain were tested at a commercial lab using only the TaqPath kit. Results for all three gene targets went to HHS from November 1, 2021, to January 14, 2023.
• Sequencing: from CDC's national strain surveillance, contracted labs and public databases. Because sequencing results lag 2–3 weeks, the most recent weeks are nowcast estimates.

What it showed

• SGTP trends matched sequencing.
• Week ending December 24, 2022: sequencing put SGTP lineages at 21.5% (XBB.1.5 11.8%, XBB 4.4%, other BA.2-related 5.3%); the pharmacy SGTP estimate was 20%.
• Week ending January 14, 2023: the SGTP estimate was 40%. Sequencing nowcasts put SGTP lineages at 50.6% (XBB.1.5 43.0%) as first reported on January 13, revised to 45.5% (XBB.1.5 37.2%) on January 20.
• SGTP made up more than 50% of specimens in HHS Regions 1–3 (the Northeast and mid-Atlantic) and more than 20% elsewhere, except Region 10, where estimates were imprecise.
• Among sequenced pharmacy specimens, 412 of 415 (99%) XBB-related sequences showed SGTP; from December 1, 2022, to January 2, 2023, 294 of 495 (59%) SGTP specimens were XBB-related.

Strengths and limits

Strengths: diagnostic PCR is cheaper, higher-volume and faster than sequencing, so emerging variants can be studied without waiting for sequencing or for a variant to become dominant. CDC and the SARS-CoV-2 Interagency Group used SGTF/SGTP data to support guidance on monoclonal antibody treatments when early nowcasts were imprecise, and early studies used it as a proxy for variants in vaccine effectiveness and severity research.

Limits: it depends on a particular test; it assumes which lineages are behind the pattern, which sequencing must confirm; it cannot tell apart lineages beyond the Δ69–70 deletion (for example, BA.4 from BA.5); and it works only while the SGTF/SGTP pattern keeps changing between dominant lineages. Sequencing remains the standard for definitively classifying lineages — SGTF/SGTP is a useful complement.

Sources

Based on Heather M. Scobie, Akilah R. Ali, Philip Shirk et al., "Spike Gene Target Amplification in a Diagnostic Assay as a Marker for Public Health Monitoring of Emerging SARS-CoV-2 Variants — United States, November 2021–January 2023," Morbidity and Mortality Weekly Report, Centers for Disease Control and Prevention (Early Release, January 25, 2023); a work of the United States government in the public domain.