Is Delta the last Covid super variant? | Coronavirus

E.Each week a group of epidemiologists in the northeastern United States joins a Zoom call devoted solely to discussing the latest evidence of new variants of Covid-19 that are being reported around the world.

“It’s like the weather report,” says William Hanage, an epidemiologist at Harvard TH Chan School of Public Health. “It used to be said, ‘We have a bit of gamma there, we have alpha here.’ But now it’s just Delta. “

The delta variant of Sars-CoV-2 has been so ubiquitous since it was first detected in India in December 2020 that one could easily assume that the once rapid development of the virus has been replaced by a dormant state. According to the World Health Organization, 99.5% of all Covid-19 genome sequences reported to public databases are now Delta.

While new tribes have kept coming up, like the youngest AY. 4.2 or the Delta Plus variant in the UK, which is estimated by scientists to be 10-15% more transmissible, although there is no exact data on this yet, they are almost identical to the Delta variant except for a few minor mutations here and there. Hanage has taken to calling them Delta’s grandsons.

“There have been a few Delta Pluss,” he says. “I recently gave a radio interview where I said Delta Plus is code for anything people are turning upside down. It is not gigantically transferable. “

But the reason Hanage and his colleagues are still scanning databases like Pangolin and Nextstrain every week, and the purpose of their regular Zoom calls, is to try to predict what might be next. Is Delta really the endgame of Covid-19 or is something more sinister looming in the future? It’s a question that no one is entirely sure of.

One possibility is that Sars-CoV-2, after the initial dramatic jumps in its genetic sequence that first produced Alpha, then Delta, is now slowly and steadily mutating and is finally out of the reach of current vaccines, but only in the course of the Time of many years. While scientists try to point out that their predictions are largely informed speculation, some consider this to be the most likely outcome.

“I assume that the type of evolution we’re about to see is more of an antigen drift, where the virus gradually evolves to escape the immune system,” says Francois Balloux, director of the UCL Genetics Institute. “With influenza and other coronaviruses, which we know quite well, it takes about 10 years for the virus to accumulate enough changes that the antibodies in the blood cannot detect it.”

Passers-by with mask in London
High virus concentrations increase the likelihood that dangerous variants will appear. “If you look at the variants that we had, they all occurred in countries with very high, uncontrolled transmission,” says William Hanage of Harvard University. Photo: Dominic Lipinski / PA

But the alternative is the sudden appearance of an entirely new strain with breakthrough portability, virulence, or immunevasive properties. Ravi Gupta, a professor of clinical microbiology at the University of Cambridge, calls these strains “supervariants” and says he is 80% certain that another one will emerge. The question is when.

“We have a delta pandemic at the moment,” says Gupta. “This new Delta Plus variant is relatively weak compared to what I mean. It has two mutations of the Delta strain, I don’t think they’re that worrying and it hasn’t seen a big boom in other countries. But it is inevitable that there will be another major variant in the next two years that will compete with Delta and potentially outperform Delta. “

There are several ways this can arise.

Will we see one Super Variant?

In the second half of 2020, epidemiologists began observing signs of a worrying phenomenon known as viral recombination, in which different versions of Sars-CoV-2 mutations exchanged and combined into an entirely new strain.

Fortunately, recombination doesn’t seem to be as common, Gupta says, but it remains a potential source for a new supervariant, especially in parts of the world where a significant portion of the population remains unvaccinated and strains of the virus can freely circulate. “Now that Delta is overwhelmingly the key virus, the likelihood has become less likely,” he says. “But there are large parts of the planet that we don’t sample, and we don’t know what’s going on. So it’s a very real possibility. “

The second is a series of major mutations that either result in a greatly improved version of Delta or something entirely different. It is believed that there is still considerable scope for this. “While newer variants are versions of Delta, the virus has enormous potential to develop in the future,” says Gideon Schreiber, professor of biomolecular science at the Weizmann Institute of Science in Israel. “More complex mutations can develop with simultaneous mutations in more than one position, which can be more problematic.”

In recent weeks there have been concerns that the use of new antiviral pills, particularly Merck’s molnupiravir, might help by actively encouraging Sars-CoV-2 to evolve. Molnupiravir works by disrupting the virus’ ability to replicate and mutating its genome until it can no longer reproduce. Some virologists have argued that if one of these viral mutants survived and spreads to others, it could, in theory, fuel the emergence of new variants. Others concede that while this should be monitored, it is not enough to prevent critically ill patients from receiving a potentially life-saving drug.

Gupta says a bigger problem, likely leading to a supervariant, is the persistently high rate of infection in countries like the UK due to Delta’s ability to transmit between vaccinated individuals. “The more infections there are per day, the greater the likelihood that someone is out there, patient X, who becomes infected and whose T cells are not strong enough to clear the infection because they are immunocompromised,” he says . “So you have the infection for several days; They have some antibodies knocking around because they had a partial vaccination reaction and the virus learns to dodge them and then it gets released.

Earlier this year, Gupta published a paper showing that this process could occur in critically ill patients given convalescent plasma loaded with antiviral antibodies. Since her immune system still couldn’t clear the virus, it learned to mutate around these antibodies. It has been speculated that the widespread use of convalescent plasma at the start of the pandemic was responsible for the appearance of variants.

“We don’t know for sure, but a lot of plasma was used and it may have been one of the drivers for the variants,” he says. “It was used very widely in Brazil, India, the UK, and the US, all of which developed their own variants.”

The arms race for the vaccination variant

Epidemiologists are now trying to model what a new supervariant might look like. So far, the major changes in the virus have helped increase its transmissibility. Hanage explains that the Delta variant had such an impact because it grows extremely quickly in human cells before the immune system gets going. As a result, people infected with Delta carry around 1,200 times more virus particles in their noses and develop symptoms two to three days earlier than the original Sars-CoV-2 strain.

This is a result of natural selection. Different copies of the virus are constantly being made, but those that have survived and become more dominant are more likely to be able to infect new people. However, this could change in countries like the UK, where the proportion of the unvaccinated population is declining. Strains that can bypass antibodies are likely to become more dominant, making the next supervariant much more likely to be able to evade at least some parts of the immune response.

The antiviral drug molnupiravir.  from Merck
Concerns have been raised that the way Merck’s antiviral drug molnupiravir works will create new mutations. However, most scientists don’t expect these to be harmful. Photo: Merck & Co Inc / Reuters

“The strains of the virus that end up surviving and becoming dominant will vary depending on what stage of the pandemic you are in,” says Hanage. “Up until now, it has been much more important that the virus is effectively transmitted into the remaining pool of unprotected people. But that is likely to change now. “

This may sound a little terrifying, but it’s not all bad news. Since the Covid-19 vaccines were designed with viral evolution in mind, epidemiologists do not expect a new supervariant that would render them completely unusable, and it would therefore be extremely unlikely that there would be large, serious outbreaks like those of the past two years.

In addition, a second generation of Covid-19 vaccines has been developed. Vaccine developer Novavax hopes to get regulatory approval for its vaccinations in the next few months, while many more vaccines are expected to hit the market by 2023. These platforms each take their own steps to combat potential future variants.

According to Karin Jooss, executive vice president and head of research and development at US pharmaceutical company Gritstone, which has a second-generation Covid-19 vaccine in Phase I clinical trials, companies are sequencing all existing strains of Sars-CoV-2 and seek to generate neutralizing antibody responses against areas of the virus that are conserved between all of these strains.

But epidemiologists also believe that simply relying on vaccines is not enough. Gupta says that even if we try to find a way to live with Covid-19 in the UK, some restrictions should still be in place to limit the spread of the virus and reduce the number of chances of mutation.

“The number of cases is so high at the moment that it is much better to prevent new infections,” says Gupta. “In other words, we shouldn’t be walking around crowded places, in buildings without a mask, even if it’s difficult. If you look at the variants we had, they all originated in countries with very high, uncontrolled transmission – India, UK, Brazil. There’s a reason we’ve never heard of a Singaporean or a South Korean variant. “

A philosophy that many of his colleagues agree with. “They want to limit the number of opportunities the virus gets to roll the dice,” says Hanage. “Natural selection is basically the most creative force we know when it comes to solving problems. It is wonderful. And that’s why you would never bet against it. We assume that the virus will continue to develop. “

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