SARS-CoV-2 Variants

Variants of Concern (VOC)

Note: These numbers are continually being updated. Because of this, the most recent datapoint on the dashboard should be cautiously interpreted—we may still be processing data from that time point. Also, these numbers only reflect cases identified by Helix and do not include cases identified by other organizations. Numbers may differ from other publicly reported dashboards due to a time lag from detection to reporting of the cases. The numbers displayed in the map graphic above show the total number of non-SGTF samples sequenced, NOT the total number of VOCs.


Background on our VOC work

Helix is working together with the CDC, local public health agencies, and other organizations on national viral surveillance efforts. Drawing from samples collected during routine lower-nasal swab COVID-19 testing, typically at Helix-supported testing sites across the country, a subset of positive samples are chosen for follow-on sequencing based on demographics, sample quality, test characteristics, or simply random selection.
 

Once raw sequencing data is generated, Helix uses Pangolin and Nextclade to identify which strain of the SARS-COV-2 virus is present in each sample, as well as its recent evolutionary relationship to other strains. The results of this work are shown in the above dashboard.
 

For Variants of Concern (VOC), we further notify State Departments of Health for contact tracing within 24 hours of receipt of sequencing results.
 

A downloadable version of the data presented above can be found here.

Trends in S gene target failure (SGTF)

What is SGTF and why does it matter?

We first reported the potential spread of the B.1.1.7 variant in the United States based on the occurrence of S gene dropout—a phenomenon where qRT-PCR testing fails to detect the presence of the virus’ S gene, owing to a deletion mutation affecting amino acids H69 and V70 (this is also known as S gene target failure, or SGTF). This deletion is one of several mutations that distinguish the B.1.1.7 from other SARS-CoV-2 strains. In these cases, qRT-PCR testing is still able to identify the presence of the virus thanks to two other targets on the virus: the N gene and ORF1 gene.

 

Subsequent viral sequence analysis of SGTF samples using Illumina’s COVIDSeq Test confirmed that only a subset of these samples harbored all variants that define B.1.1.7. The remaining SGTF samples were other variants of the virus. We have assigned each of the SGTF sequences to a phylogenetic clade in order to understand the recent evolution of this virus.

 

To monitor trends in B.1.1.7 transmission, as well as the dynamics of other variants harboring the H69/V70 deletion, we will continue to regularly sequence high-quality SGTF samples with N gene Cq<27* from our lab and place these strains on the SARS-CoV-2 phylogeny. While growing in prevalence, SGTF samples represent a small subset of all positive Helix® COVID-19 Test results. We are also expanding this surveillance program beyond SGTF samples to proactively monitor for the emergence and spread of new variants.


The interactive dashboards provided above and below are updated on a weekly basis. The above dashboard serves to specifically highlight B.1.1.7 cases in the US.


*Cq is defined by the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines as the quantification cycle and is equivalent to quantification threshold (Ct)


 

Limitations

  • Following a conservative approach, we only analyze positive samples with strong amplification of the N gene (Ct < 27), and dropout samples with absolutely no S gene detected. Because some samples may have lower viral titer, and therefore result in a weaker amplification signal, we are not analyzing all positive samples here. Therefore, the final fraction of SGTF may differ slightly.
  • Since samples are deidentified prior to analysis, and some individuals may test more than once, there may be some duplicate individuals that could cause deviation from the true population fraction.
  • Testing per state does not reflect the population distribution of the US, and therefore some states without S gene dropout may be false negatives.

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Citing the Helix® COVID-19 Surveillance Dashboard

If you use the Helix® COVID-19 Surveillance Dashboard in your research, we ask that you cite its use and include a link to this page.
 
Example: Data sourced from the Helix® COVID-19 Surveillance Dashboard. Accessed at Helix.com/covid19db on [date].

National SARS-CoV-2 Viral Surveillance

Helix and Illumina, with support from the CDC, are collaborating to augment national surveillance infrastructure in the US to track the emergence and prevalence of novel variants of SARS-CoV-2. Sequences are deposited regularly to GISAID and Genbank by the CDC. All B.1.1.7 variants are also reported to relevant public health departments for contact tracing efforts.

Helix's COVID-19 Research and Testing Efforts

In addition to conducting viral sequencing, Helix is one of the nation's largest COVID-19 laboratories—funded in part by the NIH's RADxATP program—and is helping to drive several research initiatives.

The Helix COVID-19 Test

The Helix® COVID-19 Test is a real-time RT-PCR test that received Emergency Use Authorization from the FDA in July of 2020. This expanded EUA enables both supervised and unsupervised self-collection on-site—meaning no healthcare professional is required to be on-site—our partners significantly streamline their operations and decrease their collection costs.


Clinical performance studies show a consistent limit of detection (LoD) of 1000 Viral copies / mL and was recently found to be one of the most sensitive tests on the market in a study conducted by the FDA.


Early identification of B.1.1.7

Helix researchers first reported the potential spread of the B.1.1.7 variant in the United States based on the occurrence of S gene dropout—a phenomenon where qRT-PCR testing fails to detect the presence of the virus’ S gene, owing to a deletion mutation affecting amino acids H69 and V70 (this is also known as S gene target failure, or SGTF). This deletion is one of several mutations that distinguish the B.1.1.7 from other SARS-CoV-2 variants. Subsequent viral sequence analysis of SGTF samples led to the identification of 51 of the US's first confirmed B.1.1.7 cases.

NIH Rapid Acceleration of Diagnostics (RADx) award

Helix has been awarded $33.4 M in funding from the National Institutes of Health (NIH) under the Rapid Acceleration of Diagnostics (RADx) program. These funds will support rapid scaling of our COVID-19 infrastructure and operations, with a goal of reaching a capacity of 100,000 COVID-19 tests per day.

COVID-19 Research

As this pandemic continues to unfold, Helix researchers are working with international collaborators to advance our understanding of COVID-19. Helix researchers have helped shed light on the drawbacks of saliva as a COVID-19 sample source; identify genetic factors that contribute to severe COVID-19; and are continuing to collect longitudinal survey data to help in future discoveries.

Helix Viral Surveillance Program

Frequently Asked Questions

  • Overview of the Helix Viral Surveillance Program

    Helix is working together with the CDC and other public health agencies on national viral surveillance efforts. Helix receives nasal swabs as part of our normal workflow for COVID-19 testing as the lab processing samples for several commercial partners. After processing these samples and reporting SARS-CoV-2 detection, positive samples may be selected for follow-on sequencing, based on demographics, sample quality, test characteristics (such as SGTF), or simply random selection. These samples are submitted for sequencing where they are further processed and aligned to the SARS-CoV-2 reference genome (NC_045512.2) to obtain sequencing results. Raw sequence information is transferred to Helix as well as to the CDC for nationwide testing and surveillance. Helix and/or our partners may also submit raw data, consensus sequence, and metadata to NCBI and GISAID. Helix monitors the data that becomes publicly available and, in turn, makes these identifiers available in an aggregated report in our public Github repository: https://github.com/myhelix/helix-covid19db.

    Helix further processes the sequence data to identify phylogenetic lineage and clade using Pangolin and Nextclade. These annotations are also available in our GitHub, which is the data that backs our Dashboard. For Variants of Interest or Concern (VOI, VOC) such as B.1.1.7, we further notify State Departments of Health for contact tracing within 24 hours of receipt of sequencing results.

  • What specimens are sequenced?

    We use the residual samples after completion of processing the Helix® COVID-19 Test or other COVID-19 tests as requested, which uses samples collected from anterior nares swabs in saline. The assay is a 3-gene target panel based on Thermo Fisher Scientific's TaqPath™ COVID-19 Combo Kit. You can read about our testing program here: helix.com/covid19. In order to qualify for sequencing, we require sufficient concentration of virus in the original sample. Therefore we have set a threshold of Cq(N gene) < 27, and a minimum volume of 500ul/sample.

  • How are samples selected for Helix’s viral surveillance program?

    Initial sample selection was enriched with all S Gene Target Failure (SGTF) samples from all US states to ensure identification of B.1.1.7 nationwide, as well as randomly selected additional samples for general surveillance.

    B.1.1.7 has now reached saturation of SGTF in many parts of the US, so we can simply use SGTF as a proxy for B.1.1.7 in our studies, and thereby scale down selection of these samples for sequencing. This allows us to increase widespread random sampling in order to detect other variants of concern and monitor the rise of new variants. We continue to work with the CDC to update our sampling strategy based on their feedback and public health needs.

    Not all residual samples have enough volume or enough virus particles to have success during sequencing. Regardless of sampling strategy, we filter all samples for Cq (N gene or ORF1ab) < 27 prior to sequencing to ensure robust sequencing efforts.

  • How long does it take to get a sample sequenced?

    It typically takes 1-2 weeks to sequence selected samples. As the program continues to grow, we expect the turnaround time to decrease - there are currently 2-3 sequencing runs per week. Note that this timeframe is for viral sequencing. General COVID-19 testing to detect SARS-CoV-2 usually takes less than 24 hours after receipt in the Helix laboratory.

  • Is Helix’s viral surveillance program monitored by an external committee?

    • The Helix COVID-19 biobank and viral surveillance program has been reviewed and approved by Western Institutional Review Board Protocol WIRB#20203438.
    • We are currently working with the CDC, San Diego County, and some additional partners who request individual samples be sequenced.
    • Patient privacy is our utmost concern. Within our research protocol, we have received a waiver of consent for a limited dataset under HIPAA regulations for the purposes of public health (Privacy Rule (45 CFR § 164.512(b)). The Helix research team receives no individually identifiable information beyond the limited dataset that includes sample collection date and zip code. This information is sensitive and is not revealed in the data available for public download in GitHub.

  • Does the Helix® COVID-19 Test detect B.1.1.7 or other Variants of Concern (VOCs)?

    The Helix COVID-19 Test is a 3-gene panel based on Thermo Fisher’s TaqPath assay that includes detection of the S gene. An unintended outcome of testing samples with B.1.1.7 is the inability to amplify S gene due to a nucleotide deletion in the S gene and overlapping with assay probes (also called S Gene Target Failure, SGTF). However, many SARS-CoV-2 lineages also have the same deletion mutation as is found in B.1.1.7. Only sequencing of the sample can confirm what lineage is present. The SGTF status is not reported in our standard COVID-19 test.

    Other VOCs do not have the same mutation, and at present there are no other known testing anomalies that would indicate the other VOCs. Confirmation of any VOC can only be made with viral sequencing. Viral sequencing with Helix will identify not just the variants that have already been identified as VOCs, including B.1.1.7 (UK) and B.1.351 (South Africa), but the results would enable identification and tracking of any novel variants that arise. Helix performs regular reprocessing of previously sequenced viral genomes to ensure retrospective annotation of newly classified variants.

  • Why is some of your data missing in GISAID?

    There are numerous steps that happen between a sample being sequenced and the data appearing on GISAID. After a sample is sequenced, we have to analyze and assemble the data. After that, the sequences are submitted to GISAID, which sometimes requires some troubleshooting. There is typically a 2 ½ week lag from collection of the initial sample to upload of the data on GISAID, but may be longer for some samples.

  • How do I access FASTA files, information in GISAID, and raw sequencing results (BAMs, FASTA)?

    Sequencing data generated from samples originating at Helix can be obtained from two public repositories: GISAID and NCBI. Deposition into these public repositories is being done by our collaborators at CDC and Scripps.

    All samples that originate at Helix should have “STM” in the sample name. This string can be used when searching for samples at NCBI or GISAID.

    In order to assist with your research, you can find a summary of the sequence data at our public GitHub repository here: https://github.com/myhelix/helix-covid19db

  • How can I get a complete list of sequenced samples for my state?

    We make limited metadata including State and NCBI accession number for Helix samples available on our public GitHub repository, which can be used to filter for your state of interest: https://github.com/myhelix/helix-covid19db

  • I want to find out more about this program. Who do I contact?

    For press inquiries, please contact press@helix.com.
    For establishing new viral surveillance programs with Helix, please contact covid@helix.com.
    For public health reporting, please contact dphreporting@helix.com.
    For research questions, please contact research@helix.com.
    Follow @my_helix on Twitter where we will update about the program and significant research findings.

Contact us to learn more about our COVID-19 testing and research

For press inquires, please email press@helix.com

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