New variants pose fresh test for UK’s Covid defences

Two cases of a new and concerning coronavirus variant, originating from the Philippines, have been identified in England, posing a new challenge to the UK’s defence against mutant strains.

The variant, named P.3, was reported by Philippine officials on March 9, and includes a number of similar mutations to variants that have either been detected after arriving from overseas or evolved through transformations on British shores.

So far the UK has proved successful in preventing concerning variants from spreading like wildfire across its population. But experts believe their relatively modest proliferation to date stems at least in part from the fact that the UK’s homegrown “variant of concern” — first identified in Kent and known as B.1.1.7 — has an evolutionary advantage over new arrivals.

“It is increasingly clear that the other variants of concern are not as transmissible as B.1.1.7 in the UK,” said Dr Jeffrey Barrett, director of the Covid-19 genomics initiative at the Wellcome Sanger Institute.

Barrett noted that the intense national lockdown may have also contributed to the fact that “sparks” of concerning variants from around the world “have repeatedly landed this year but haven’t grown out of control”.

Scientists believe that on average Sars-Cov-2, the virus that causes Covid-19, acquires about two mutations a month, around half the rate of influenza and one quarter that of HIV. But only a few of these random genetic changes are a cause for concern.

One such lineage, known as 501.v2, was first found in South Africa late last year and emerged in the UK shortly afterwards. Several studies have suggested it is more transmissible, more lethal and better at evading vaccines than several of its predecessors. However, in the past six weeks, the number of cases in the UK has risen from 77 to just 344.

P.1, which originated from Brazil, also sent chills through government when six cases were identified in late February. Concerns about its rapid spread were exacerbated by studies that found it was around twice as transmissible as other strains circulating in Brazil and was able to evade natural immunity conferred by prior infection. 

Three weeks after its arrival in the UK, the number of P.1 cases detected has risen to only 12. 

Other variants of concern include the latest, P.3 from the Philippines, and another version of B.1.1.7 detected in the UK that has gained a mutation known as E484K to the spike protein, which the virus uses to pierce through human cells.

Some commentators argue that the spread of these variants has been limited at least in part by the government’s rapid containment strategy.

This series of new strains — all of which share intriguing genetic similarities — were seen as the ultimate challenge to the government’s £37bn test and trace programme, which has faced ongoing criticism for failing to have a significant impact on the epidemic curve.

Senior officials at test and trace point to the identification of the first six people infected with the P.1 strain — including a mystery person who was found in south London after a week-long hunt — as a testament to the skill of local and national teams working together to investigate small pockets of cases.

B.1.1.7 is currently believed to be the most transmissible lineage in the UK, causing about 97 per cent of disease, and has been found to be between 30 and 100 per cent more lethal than previous strains.

Professor Sharon Peacock, of Cambridge university, has said that it is “on course to sweep the world”, noting that it has become very dominant in every country it has reached. It now accounts for about 40 per cent of cases in the US and France.

Some have questioned whether enough was done to contain B.1.1.7 after it was identified in September. But Peacock insisted that when it first appeared it was one among 332,000 genomes in the UK’s database and it was unclear at that time whether its mutations would give it an evolutionary advantage. 

While it is becoming increasingly clear that B.1.1.7 has the upper hand over its closely related competitors, experts have cautioned that the balance of power may shift as the vaccination campaign gains pace.

This is because some of the new variants, such as P.1 and 501.v2, have shown warning signs that they can at least partially evade vaccine induced immunity, which B.1.1.7 cannot.

“The fraction of the population with immunity is going up very fast now thanks to vaccines,” said Barrett. “We’ll need to watch very closely as [lockdown measures] are eased.”

The UK’s ability to monitor the advance of these new variants is in large part a product of its world class skills in genomic sequencing, the complex process of reading the entire genetic code of an organism.

The UK is one of just a handful of countries, including South Africa and Denmark, that invested significantly in this niche and relatively young scientific field before the pandemic struck.

In March of last year, Peacock, who has been working in genomic sequencing since 2009, messaged five colleagues asking if they would be interested in setting up a team to monitor the real-time evolution of Sars-Cov-2.

A few weeks later, she had convened 16 sequencing labs under the umbrella of the Covid-19 Genomics UK (Cog-UK) consortium, and has since received more than £32m in funding from the UK government and the Wellcome Sanger Institute, which also does a large proportion of sequencing work for the government.

The UK is now able to sequence about 30,000 genomes a week from around 50,000 a year before the pandemic. The process — which involves breaking down, sequencing and reassembling the virus’s genetic code like a giant jigsaw puzzle — now takes about four days.

Six of the 10 variants of concern in the UK contain the same E484K mutation — nicknamed Eric or Eek — which alters the surface of the spike protein. This makes it harder for the immune system to recognise and destroy the virus, if it has been trained by vaccines based on previous forms.

Another common change responsible for increased virus transmission is the spike protein’s N501Y mutation, found in B.1.1.7 as well as those from South Africa, Brazil and the Philippines.

The scientific community is divided as to whether this “convergence” of genetic changes suggests that the virus has reached peak fitness, meaning any future mutations will make it less harmful, or whether more cunning adaptations are inevitable as vaccines apply greater evolutionary pressure.

“We’ve reached a plateau,” Peacock said, “but what we don’t know is whether there’s more in store”.