How genomic sequencing can spot the next coronavirus variant

A new coronavirus variant that fuses elements of Delta and Omicron was identified last week, according to the World Health Organization and GISAID, the organisation that tracks the mutation of viruses. Its detection, say experts, highlights the important role played by genomic surveillance.

It has been detected in several regions of France, and in Denmark, the Netherlands and Germany. The variant has been in circulation since January. The WHO said it is not yet clear whether the variant is distinct from its predecessors in terms of infectiousness or severity, though studies are under way.

Two years after the WHO declared Covid-19 a pandemic, global cases are beginning to subside but it still kills 50,000 people a week. Around 6mn people have died in the pandemic, according to official data from governments, although a recent study suggests the true number of Covid-related deaths may be three times higher.

Public health officials have urged against complacency as countries around the world drop restrictions that were imposed to stop the spread of the disease. “We still face the threat of new Covid variants that could be more severe, they could be more transmissible or they could even escape the protection of current vaccines,” Sajid Javid, UK health secretary, said last week.

Epidemiologists agree that the emergence of viral variants will be the most important factor driving the course of the pandemic. Swift identification of variants of concern will play a key part in preventing future public health crises.

How do scientists identify and track new variants?

The main way is through “genomic sequencing” of samples taken from Covid PCR tests. The genetic code of Sars-Cov-2 — its genome — is stored as a sequence of four biochemical “bases” strung out along a long molecule of RNA.

To read the genome, scientists convert RNA to DNA, a closely related molecule that stores the genetic material in living cells. The genetic sequence of the virus can then be read by machines that are also used to decode human, animal, bacterial and plant DNA.

At the Wellcome Sanger Institute, the UK’s largest sequencing centre, it typically takes about five days to transfer samples from testing labs around the country to the sequencing machines and then two days to read out all 30,000 biochemical “letters” of the viral genetic code in each sample.

“It’s a big logistical operation,” said Ewan Harrison, a specialist in microbial genomics at the institute.

An alternative to analysing viruses from infected individuals is collective genomics, using samples of sewage and wastewater that retain traces of coronavirus excreted by people. This technology is becoming sensitive enough to distinguish different viral variants rather than just the presence of Sars-Cov-2 in the area.

“Wastewater monitoring has made some leaps forward during the pandemic and it is going to be part of surveillance in future,” said Harrison, “but it can never tell us as much as sequencing of individuals along with patient data that can tell us about the biology of the variant.”

Why is surveillance so important?

Surveillance through genomic sequencing must be maintained at an effective level worldwide to identify new threats as governments scale back Covid testing, said Peter Bogner, GISAID’s chief executive.

“If we were to ramp down testing overall, there is a significant risk that we would miss several new variants,” Bogner said. “The power of a good sampling strategy is that relevant changes can be captured effectively. But such surveillance efforts have to be done globally.” 

Importantly, recombination — when two molecules of DNA exchange pieces of their genetic material with each other — is to be expected, WHO officials and others have said, especially given the high viral circulation levels in the background. It is also quite common in influenza viruses.

How are different countries approaching testing and sequencing?

Wealthier countries such as the US and European nations typically sequence more than poorer counterparts. Much of this difference is due to advanced economies having more trained personnel and better access to the hardware — machines and reagents — needed to perform genomic sequencing.

Experts say Omicron exposed the extent to which inequalities in the handling of the pandemic were not confined to supply of vaccines or tests and extended to key tools like sequencing.

But sequencing in places with fewer resources can still yield powerful results, such as in South Africa.

Tulio de Oliveira, a bioinformatics professor at Stellenbosch University and one of the scientists behind the discovery of the Beta and Omicron variants, said countries with large resources and low infection rates, such as Denmark and Australia, could sequence “almost everything” before the arrival of Omicron. But that approach is no longer as viable when cases rise because sequencing cannot keep up with the number of cases.

De Oliveira said his team has since March 2020 focused on random and proportional sequencing each week. It means his researchers select provinces randomly and focus on samples to be sequenced in keeping with case numbers.

How concerned should we be about the new variant?

De Oliveira said he was not particularly concerned by the recombinant variant — which is yet to be named by scientists but has been dubbed Deltacron in some media reports — because of the small case numbers amid decreasing overall infections and rising vaccination rates.

“We are alert but we are not concerned,” he said.

Maria Van Kerkhove, the WHO’s Covid-19 technical lead, said it was too soon for people to be worried. “We have not seen any change in the epidemiology . . . [or] in severity,” she said, adding that a number of studies are under way.

What is the likelihood of a more pathogenic variant emerging and how likely are we to spot it?

Virologists are unanimous in the view that new variants will emerge. However, no one can predict the timing of their appearance or how virulent they are likely to be.

“We caution that the milder symptoms in the human population, and in animal models, associated with the Omicron variant compared with previous variants, is likely a chance event,” warned Nervtag, a group of health experts who advise the UK government on new and emerging viruses. “The loss of virulence as viruses evolve is a common misconception.”

GISAID’s Bogner said the identification of the recombinant variant “underscores the indispensable need for effective surveillance, as a ramping-down of testing overall bears the significant risk that we would miss recombinant viruses as the virus evolves”. 

“But such surveillance efforts have to be done globally and with a good sampling strategy,” he added.