Understanding Covid variants

Andy Felton on sequencing the SARS-CoV-2 genome to identify variants and inform community action

The Covid-19 public health crisis has continued to evolve since cases first began spreading. Although it was initially believed that mutations would have little impact on how the virus spreads, researchers quickly learned this was not the case. There are now thousands of different variants circulating around the world, some containing between 15-30 distinct mutations, with new strains becoming increasingly infectious due to selective pressures.

As new strains continue to emerge, there is an urgent need to understand not only if patients are Covid-19 positive or negative, but also what strain they are infected with to inform public health responses. Although global surveillance efforts are underway, there is also a need at the community level for rapid, cost-effective SARS-CoV-2 surveillance to help local public health officials quickly identify any potential outbreaks and make real-time, data-driven decisions on guidelines such as business openings, access to recreational sites and in-person learning.

Over the past year, we’ve seen rapid innovation and iteration in molecular technologies to try and gain a better understanding of Covid-19. In addition to the PCR tests used for diagnosis and population-scale screening, a dire need exists to ramp up viral genome sequencing to understand and track how SARS-CoV-2 is mutating. Next-generation sequencing (NGS) offers the full picture of the SARS-CoV-2 genome, capturing mutations across the virus to identify if a sample represents a new or known variant.

The CDC has announced that rapid genetic sequencing will be part of its overall strategy for managing this pandemic, and researchers globally are getting involved to provide more comprehensive sequencing coverage. To that end, Thermo Fisher Scientific has been working closely with many of these labs since the spring of 2020 to sequence millions of samples.

 As one example, Thermo Fisher helped North Carolina-based reference lab Mako Medical quickly ramp up NGS testing capacity in partnership with the CDC to identify emerging SARS-CoV-2 variants. Equipped with Thermo Fisher’s high-capacity sequencing platforms, Mako is sequencing samples from 43 states and has the capacity to process 6,000 positive Covid samples a week. The company is working with the CDC to increase awareness of what variants are circulating and monitoring new variants as they appear. It has observed 55 different lineages since May 2021, and is currently sequencing nearly all positive samples. In addition, with vaccinations increasing, Mako is regularly asked by state health departments to sequence specific samples from “breakthrough” infections in people who have been fully vaccinated to gain a better understanding of vaccine efficacy against new and emerging variants of concern.

In the UK, Oncologica, a private precision oncology lab, worked with Thermo Fisher to pivot from cancer sequencing to SARS-CoV-2 sequencing. With this new capability, Oncologica is partnering with the International Travel Testing Programme to sequence positive samples from travellers arriving in the country to better understand how variants are moving across borders.

To continue to support these programmes and the need for real-time insights, Thermo Fisher introduced the Ion Ampliseq SARS-CoV-2 Insight Research Assay, a highly sensitive assay for sequencing SARS-CoV-2 samples, including those samples with lower viral loads.

The assay leverages a targeted sequencing approach that yields improved coverage and uniformity from samples previously inaccessible by NGS. Given SARS-CoV-2 is mutating so rapidly, it is hard to predict where the next mutation is going to occur; labs need a tool that doesn’t exclude regions of the SARS genome based on existing known mutations, but instead provides a complete picture of the virus’ genetic makeup. By sequencing more than 99 percent of the SARS-CoV-2 genome, including all known serotypes, the assay provides increased resilience against the impact of new and emerging mutations.

Andy Felton is with Thermo Fisher Scientific

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