Every week, a group of epidemiologists across the north-east of the United States joins a Zoom call entirely devoted to discussing the latest hints of new Covid-19 variants being reported around the world.

"It's like the weather report," says William Hanage, an epidemiologist at the Harvard TH Chan School of Public Health. "It used to be, 'We have a little bit of Gamma there, we've got Alpha coming up here.' But now it's just Delta."

Since it was first detected in India in December 2020, the Delta variant of Sars-CoV-2 has become so ubiquitous that it would be easy to assume that the once-rapid evolution of the virus has been replaced by a state of quiescence. According to the World Health Organization, 99.5% of all Covid-19 genomic sequences reported to public databases are now Delta.

While new strains have continued to emerge, such as the recent AY. 4.2 or the Delta Plus variant in the UK, which scientists estimate to be 10-15% more transmissible, although there is no exact data for this yet, they are almost identical to the Delta variant, apart from the odd minor mutation here and there. Hanage has taken to referring to them as Delta's grandchildren.

"There's been quite a few Delta Pluses," he says. "I did a recent radio interview where I said that Delta Plus is code for whatever people are getting their knickers in a twist about at the moment. It's not gigantically more transmissible."

But the reason Hanage and colleagues still scan databases such as Pangolin and Nextstrain each week, and the purpose of their regular Zoom calls, is to try and predict what might come next. Is Delta really Covid-19's endgame or is something more ominous looming in the future? It is a question to which no one is entirely sure of the answer.

It's inevitable there will be another significant variant in the next two years – and it may out-compete Delta

Prof Ravi Gupta, University of Cambridge

One possibility is that after the initial dramatic jumps in its genetic sequence, which gave rise to first Alpha, then Delta, Sars-CoV-2 will now mutate slowly and steadily, eventually moving beyond reach of the current vaccines, but only over the course of many years. While scientists are at pains to point out that their predictions are mostly informed speculation, some perceive this as the most likely outcome.

"I anticipate that the kind of evolution we will see is more what we call antigenic drift, where the virus gradually evolves to escape the immune system," says Francois Balloux, director of the UCL Genetics Institute. "For influenza and other coronaviruses we know quite well, it takes about 10 years for the virus to accumulate enough changes not to be recognised by antibodies in the blood."

But the alternative is the sudden appearance of a completely new strain, with game-changing transmissibility, virulence or immune-evasive properties. Ravi Gupta, professor of clinical microbiology at the University of Cambridge, refers to these strains as "super variants" and says he is 80% sure that another one will emerge. The question is when.

"We've got a Delta pandemic at the moment," says Gupta. "This new Delta Plus variant is relatively wimpy compared to the kind of thing I'm talking about. It has two mutations from the Delta strain, I don't think they are that worrisome and it hasn't taken off in a big way in other countries. But it's inevitable that there will be another significant variant in the next two years and it will compete with Delta and it may out-compete Delta."

There are a number of ways in which this might arise.

Will we see a  super variant?

During the latter half of 2020, epidemiologists began to observe signs of a concerning phenomenon known as viral recombination, in which different versions of Sars-CoV-2 exchanged mutations and combined to form a totally new strain.

Thankfully, Gupta says recombination does not appear to be that common, but it remains one feasible source of a new super variant, particularly in parts of the world where sizable proportions of the population remain unvaccinated and viral strains can circulate freely. "Now that Delta is overwhelmingly the key virus, this has become less likely," he says. "But there are large swaths of the planet that we're not sampling and we don't know what's going on. So it is a very real possibility."

More complex mutations can evolve in the future, which may be more problematic…