Swift Biosciences Inc. released an S gene panel for SARS-CoV-2 that covers 100% of the gene even with minimal viral titers. The S gene controls the spike protein, which enables the virus to bind to cells and affects transmissibility, and has accumulated multiple mutations in the concerning variants recently discovered in the U.K., South Africa, Brazil, Denmark and the U.S. The panel is expected to enable rapid scaling of surveillance efforts of the new strains and can be run by any lab using the Illumina system, the most common instruments for next generation sequencing (NGS).
"The S gene panel allows the scientific community to rapidly scale surveillance efforts and prioritize monitoring of emerging strains that are highly infectious due to mutations which encode for the spike protein," said Swift Biosciences Director of Manufacturing Sciences Jordan RoseFigura.
Emerging strains with S gene mutations and likely increased transmissibility have spread rapidly around the world and across the U.S. The U.K. variant has appeared in 70 countries and 28 states and is expected to be the dominant strain in the U.S. by March. The South African strain is known to be in 31 countries and was first detected in the U.S. in two samples from South Carolina on January 27, 2021, in individuals with no travel history. The Brazilian variant has been reported in at least six countries and, recently, in Minnesota; the Danish variant has spread throughout California and a homegrown variant that dominates in Columbus, Ohio, has also been detected in six other states.
While an increase in cases associated with greater infectivity is enough cause for alarm, recent research indicating that the U.K. variant may be 30% to 40% more virulent and that the South African strain could limit the effectiveness of antibody cocktails and plasma treatments ups the ante. Likewise, analyses suggest that the Brazilian variant may evade detection by antibodies in individuals who have already had COVID-19, enabling reinfection.
To get a better handle on their spread, the U.S. has ramped up its surveillance efforts to better identify new strains of SARS-CoV-2 and quickly identify emerging hot spots fueled by these more transmissible variants. That includes increasing the role of the U.S. CDC’s national genomics consortium, established last spring to coordinate, standardize and share SARS-CoV-2 genomic sequencing data. To date, efforts by the SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology and Surveillance (SPHERES) consortium have been fragmented and underfunded.
The new administration aims to make the program more centralized and efficient and to sharply increase the rate of sequencing. Currently ranked 43rd in the world for its rate of sequencing, the U.S. sequences about 0.3% of COVID-19 samples. In comparison, the U.K. sequences 5% of its samples.
Ann Arbor, Mich.-based Swift, a member of SPHERES, provides research and surveillance tools and technology to the consortium to aid in timely genomic sequencing and facilitate the development of diagnostics, therapeutics, and mitigation strategies to combat the virus, RoseFigura told BioWorld. The open source consortium provides access to data to researchers all over the U.S. to improve understanding of the novel coronavirus and its spread.
Upping the number of samples sequenced dramatically requires some simplification of the process and expansion of the labs able to do the sequencing.
Swift’s Swift Normalase Amplicon SARS-CoV-2 S Gene Panel (SNAP) facilitates more sequencing in several ways. It allows “researchers to sequence a higher number of samples more quickly by eliminating the tedious, time-intensive qPCR library quantification step,” RoseFigura said. Normalized complement DNA (cDNA) libraries are typically required to identify and analyze rare transcripts.
Further, “[t]he rapid protocol allows researchers to move from cDNA to sequencer in three hours. This enables labs to sequence samples that test positive for COVID and know within 24 hours which strains are in the local population.”
By focusing on the S gene, the panel enables “researchers to sequence a higher number of samples more deeply in order to identify current strains as well as emerging strains,” RoseFigura added. “Given the variants in the S gene that could impact the efficacy of available vaccines, focusing on the S gene can bring an important tool to surveillance and understanding of SARS-CoV-2.”
The panel incorporates redundancy to ensure it captures any novel variant, including dropouts. That’s important as strains with a specific deletion (H69del/V70del) such as the U.K. variant, has S gene dropout in PCR tests.
If variants in the E, M or N genes become more important, researchers could use Swift’s extended genome panel, SNAP with Additional Genome Coverage, to capture mutations in all genes. Targeted panels for study of the ACE2 receptor and for hybridization-capture of the virus from RNA libraries, with Arbor Biosciences, are also available.