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

Abstract

Monitoring emerging SARS-CoV-2 lineages and their epidemiologic characteristics helps to inform public health decisions regarding vaccine policy, the use of therapeutics, and health care capacity. When the SARS-CoV-2 Alpha variant emerged in late 2020, a spike gene (S-gene) deletion (Δ69-70) in the N-terminal region, which might compensate for immune escape mutations that impair infectivity (1), resulted in reduced or failed S-gene target amplification in certain multitarget reverse transcription-polymerase chain reaction (RT-PCR) assays, a pattern referred to as S-gene target failure (SGTF) (2). The predominant U.S. SARS-CoV-2 lineages have generally alternated between SGTF and S-gene target presence (SGTP), which alongside genomic sequencing, has facilitated early monitoring of emerging variants. During a period when Omicron BA.5-related sublineages (which exhibit SGTF) predominated, an XBB.1.5 sublineage with SGTP has rapidly expanded in the northeastern United States and other regions.

FIGURE

Trends in estimated proportions of SARS-CoV-2 reverse transcription–polymerase chain reaction test results with S-gene target presence and variant proportions and nowcast projections from genomic surveillance classified by S-gene target presence or S-gene target failure* — United States, November 1, 2021–January 14, 2023 Abbreviations: S-gene = spike gene; SGTF = S-gene target failure; SGTP = S-gene target presence. * Estimates of variant proportions and nowcast projections (for the most recent 3 weeks) are shown. The Delta (B.1.617.2) variant exhibited SGTP; the Omicron (B.1.1.529) variant and BA.1.1 sublineage exhibited SGTF; the Omicron BA.2 and BA.2.12.1 sublineages exhibited SGTP; Omicron BA.4 and BA.5 sublineages (which have the same spike sequence), BA.4-related (BA.4.6) and BA.5-related sublineages (BA.5.2.6, BQ.1, BQ.1.1, BF.7, and BF.11) exhibited SGTF; and BA.2-related sublineages (BA.2.75, BA.2.75.2, BN.1, XBB, and XBB.1.5) exhibited SGTP. The spike deletion (Δ69-70) that results in SGTF is not 100% penetrant in a lineage; SGTF/SGTP classification was made based on a 50% threshold. Most BA.2-related sublineages exhibit >99% SGTP.