The Delta variant has been caged. Whisper it, but this may all be over soon

But what is the likelihood of this happening? What exactly is the scale of the variant threat?

Virologists are, in fact, cautiously hopeful that the danger is not as bad as feared. Nobody is certain, of course. The experiences of December and April are too fresh in the mind for any expert to rule out the possibility of a drastic turn of events.

But some are now willing to stick their heads above the parapet. “I suspect we won’t get a major surge of new variants,” said Paul Hunter, professor of health protection at the University of East Anglia. “People who continuously warn about new variants are, I think, mistaken.”

To understand his optimism, it is worth explaining how and why viruses mutate. When the Sars-CoV-2 virus jumped from bats to humans in late 2019, it was the first time it had come into contact with human cells. The virus was able to latch on, infect the cells, and replicate itself. And it spread from person to person.

Scientists believe there is a slim chance of a new variant emerging that would evade vaccines completely

TIM P. WHITBY/GETTY IMAGES

Over the next few weeks and months, its ability to undergo this process improved. Every time it replicated, there were minor mutations. Evolutionary pressure meant the most transmissible mutations — those that made the virus better at latching onto cells — spread the most effectively. When the Wuhan virus spread through China in January, every patient transmitted it to an average of 2.6 others. By the time it had reached Europe, this figure — which scientists call the R₀ — had risen to 3. The Alpha variant increased this to about 4, and the Delta to between 6 and 8.

But this process has its limits. “In the first year, increased transmissibility is important,” Hunter said. “But there is a maximum fit [between the virus and the human body] that can be achieved.” He pointed out that all four main variants of concern now in circulation appeared in the space of a few months. While others have since emerged, none has taken off. “Once that maximum fit is achieved the appearance of new variants slows dramatically,” he said.

This process is elegantly explained in a paper published in the Nature Reviews Microbiology journal in May 2019, before Covid burst into the world. “There seems to be a beautiful paradox in virus evolution,” the Oxford University scientists wrote. “The same remarkable ability of viruses to rapidly adapt to new hosts ... may also help to create the evolutionary stasis of viruses in long-term host relationships.”

The virus has to be able to continue the process of infection, replication, and reinfection. If it makes too many mutations, evolves too far, it loses its ability to coexist with its host. “We might describe this constraint as a cage,” the scientists wrote.

Hunter believes the virus has now reached the bars of that cage. “I think Delta is probably going to be the best fit,” he said.

Delta has remained remarkably stable since it emerged. A sublineage that is thought to have emerged in Nepal, which included a worrying additional mutation, never spread far.

Jonathan Ball, professor of virology at Nottingham University, said: “I think very often a virus has to trade off in one area with fitness in another. It just finds a middle ground.”

Virtually all other variants have been driven off by the far more transmissible Delta, which now makes up more than 99 per cent of British cases. “As soon as Delta comes along everything else turns up its toes and dies,” Hunter says.

So does that mean the virus will not mutate at all? Not quite. The first type of mutation affects transmissibility, and is driven by the virus adapting to human cells. But there is a second type of evolution — the “escape” mutation — which is driven by the virus adapting to the immune system. As our bodies learn to kill the virus, either through infection or vaccination, the virus adapts to try to hide from it.

The Beta variant, which first appeared in South Africa, and the Gamma variant, which appeared in Brazil, both have mutations that allow them to reinfect people and to evade the vaccines. Delta, to a less extent, has also evolved to escape immunity.

So should we fear these escape mutations? After all, vaccines are our route out of the crisis. If a new variant emerged which was to evade them completely, we would be back to square one.

But the odds of that happening are quite slim. All the vaccines at our disposal are at least partly effective against the various variants of concern. According to a new Canadian study of 70,000 people, the AstraZeneca jab, the one bypassed most effectively, is still 50 per cent effective against symptomatic infection with Beta or Gamma after a single dose. And it remains 82 per cent effective against hospital admission or death. The Pfizer and Moderna vaccines provide even greater protection.

A variant that could render that immunity entirely redundant would have to make a significant evolutionary leap. That leap is unlikely, again because of the “cage” that constrains viral mutation.

The Covid vaccines work by teaching the immune system to recognise the spike protein, a microscopic protrusion on the outside of the Sars-CoV-2 virus that latches onto human cells. The virus evades immunity by altering the spike protein in subtle ways, so antibodies can no longer recognise it quite so well.

But the spike protein can be altered only so far while retaining the ability to latch on. Beyond a certain evolutionary point, the further the virus moves away from the original, the less effective it will become at infecting human cells. The virus comes up against the bars of the cage once more.

And what if it does work out a way to escape? The immune system will respond. Hunter believes we will see minor mutations “every three, four or five years”.

He said: “If you look at other human coronaviruses you see these regular escape mutations, but it doesn’t mean everybody’s susceptible again, it’s just a bit more resistant to prior immunity.”

Anthony Fauci, chief medical adviser to the US president, described in a 2008 paper how the virus that caused the Spanish flu pandemic of 1918-19 had continued to circulate through the decades. But while it initially caused devastating disease, killing 50 million worldwide, nearly a century later it was relatively benign, occasionally mutating enough to cause a winter outbreak, but then being brought under control as immunity was reasserted.

“The 1918 influenza virus and its progeny, and the human immunity developed in response to them, have for nearly a century evolved in an elaborate dance,” Fauci wrote. “The partners have remained linked and in step, even as each strives to take the lead.”

Most scientists agree that Covid is not going away. We will continue to live with the virus for generations. But perhaps it will follow a similar path to that of Spanish flu, constrained in the cage of its human host, evolving and mutating and occasionally escaping, in a dance in step with our immunity.

Perhaps the Delta variant will be as bad as it gets. If so, but whisper it, the worst of the pandemic may soon be behind us after all.