Study population and setting
Routine RT-quantitative PCR diagnostic testing for SARS-CoV-2 relies on detection of the N and S genes. Genetic changes in viral variants, including a small deletion found in the B.1.1.7 variant, can prevent detection of the S gene, an anomaly referred to as S gene target failure (SGTF); samples with SGTF are considered positive based on detection of the N gene alone. Authors analyzed rates of SGTF in 0.5 million SARS-CoV-2 positive samples tested at Helix facilities in the United States between July 2020 and January 2021. Samples with SGTF (n=460) were sequenced in order to quantify B.1.1.7 prevalence in cases of both SGTF and SARS-CoV-2. Phylogenetic analysis was performed using genomic sequences from 212 confirmed B.1.1.7 samples collected between December 2020 and January 2021, combined with 292 international B.1.1.7 background sequences. These data were used to describe the introduction and early community spread of the B.1.1.7 variant in the United States. Estimated growth rates were used to predict the continued spread of the variant through the spring of 2021.
Summary of Main Findings
Rates of SGTF in the United States increased from 0.8% to 4.2% over the month of January 2021. By mid-January, the proportion of B.1.1.7 variant samples identified among nationwide SGTF samples was ~90%, and the overall prevalence of B.1.1.7 among COVID-19 cases was ~2.1%. Models estimating growth of the B.1.1.7 variant in the United States demonstrate an increased transmissibility of 35-46%. As such, the B.1.1.7 variant should become the dominant strain of SARS-CoV-2 in the United States by early March 2021. Phylogenetic analysis revealed at least eight independent introductions of the B.1.1.7 variant to the United States, beginning in late November 2020. Clustering of sequences from persons living in different states illustrates evidence of community transmission of the variant. Two additional mutations identified in B.1.1.7 samples from Florida illustrate ongoing variant evolution; one of these (Q349K) may play a role in evasion of the host immune response.
This study represents the largest volume sequencing effort targeted to include SARS-CoV-2 B.1.1.7 variant genomes in the United States. The strategy of only including samples with SGTF for sequencing allowed for effective enrichment of B.1.1.7 variant data.
Sequencing data collected through a national SARS-CoV-2 surveillance program would have provided a broader and more unbiased sample of variants across the United States. However, this project relied on sequencing residual diagnostic samples collected from Helix facilities, whose national coverage is uneven. This may have introduced sampling bias and may be responsible for the failure to identify the B.1.1.7 variant in some states. Additionally, both undersampling and sequencing bias may have impacted phylogenetic analysis, limiting clustering accuracy and the ability to estimate directionality of transmission. Finally, deidentification of B.1.1.7 samples prior to this study may have led to the inclusion of duplicate test results from the same individual, impacting prevalence and transmission estimates.
This study is the first to describe the genomic epidemiology of the SARS-CoV-2 B.1.1.7 variant in the United States. This work clearly illustrates how national genomic surveillance programs would enhance public health efforts to mitigate the impact of B.1.1.7 and other variants of concern, including those not yet identified.
This review was posted on: 5 March 2021