Is Delta the last Covid “super variant”? | Coronavirus

EVery weekly, a group of Northeastern U.S. epidemiologists will join a zoom call dedicated entirely to discussing new and up-to-date tips. COVID-19 Subspecies reported all over the world.

“It’s like a weather forecast,” says William Hanage, an epidemiologist at Harvard TH Chan Public School. health.. “In the past,’there’s a bit of gamma. Here’s alpha.’ But now it’s just a delta.”

Since its first detection in India in December 2020, the Sars-CoV-2 delta mutant has become highly ubiquitous, making it easy to speculate that the once rapid evolution of the virus has replaced the quiescent state. increase. According to the World Health Organization 99.5% of all Covid-19 genomic sequences It is currently Delta that is reported to the public database.

New strains such as the recent AY continue to emerge. 4.2 or Delta Plus British variant, this Scientists estimate We don’t have accurate data on this yet, but they are pretty much the same as the delta variants, except for the weird minor mutations here and there, because they are 10-15% transmissible. Hanage calls them the grandchildren of Delta.

“There were quite a few Delta Plus,” he says. “I did a recent radio interview, where I said Delta Plus is the code for those who are currently twisting. It’s not hugely contagious.”

But why Hanage and colleagues still scan databases like this: Pangolin When Nextstrain The purpose of weekly and regular Zoom calls is to predict what will happen next. Is Delta really the end of Covid-19, or is there something more ominous in the future? It’s a question no one is completely sure of the answer.

One possibility is that after the first dramatic jump in the gene sequence that gave rise to the first alpha and then the delta, Sars-CoV-2 mutated slowly and steadily, eventually in the current vaccine. Moving beyond reach, but only for the entire course for many years. Scientists have a hard time pointing out that their predictions are mostly informed guesses, but some recognize this as the most likely result.

“I expect the type of evolution we see to be so-called antigenic drift, in which the virus evolves slowly to escape the immune system,” he said. François Burrow, Director of the UCL Institute of Genetics. “In the case of influenza and other coronaviruses that we are familiar with, it takes about 10 years for the virus to accumulate changes that are not recognized by antibodies in the blood.”

However, an alternative is the sudden emergence of a brand new strain with game-changing transmissible, pathogenic, or antigenic properties. Ravi GuptaA professor of clinical microbiology at the University of Cambridge calls these strains “supervariants” and states that he is 80% confident that another strain will emerge. When is the problem?

“Currently, there is a Delta pandemic,” says Gupta. “This new DeltaPlus variant is relatively weak compared to what I’m talking about. There are two mutations from the Delta strain, I don’t think they’re too worrisome, and It hasn’t taken off much in other countries, but it’s inevitable that in the next two years there will be another significant variant that can compete with and surpass Delta. “

There are several ways this can happen.

Do you see wonderful Mutant?

In late 2020, epidemiologists began observing signs of a feared phenomenon known as viral recombination. In this phenomenon, different versions of Sars-CoV-2 exchanged mutations and combined to form a whole new strain.

Thankfully, Gupta seems to be less common in recombination, but is new, especially in parts of the world where a significant proportion of the population remains unvaccinated and viral strains are free to circulate. It states that it is one of the viable sources of supervariants. “Now that Delta is the overwhelmingly important virus, this is unlikely,” he says. “But there is a wide range of planets we haven’t sampled and we don’t know what’s going on, so that’s a very realistic possibility.”

The second is a series of major mutations, with Delta versions significantly enhanced or very different. It is believed that this is still quite possible. “A recent variant is the Delta version, but the virus is very likely to evolve in the future,” he said. Gideon Shriver, Professor of Biomolecular Science, Weizmann Institute of Science, Israel. “More complex mutations can evolve, and mutations can occur at multiple locations at the same time, which can be more problematic.”

In recent weeks, there have been concerns about the use of new antivirals, especially Merck tablets. Molnupiravir, Sars-CoV-2 can contribute to this by actively encouraging its evolution. Molnupiravir works by blocking the virus’s ability to replicate and spreading mutations in the genome until it can no longer replicate. Some virologists claim If any of these viral variants survive and spread to others, it could theoretically spur the rise of new variants. Others admit that while this is worth monitoring, denying potentially life-saving drugs to critically ill patients is not a sufficient concern.

According to Gupta, the bigger problem and more likely to lead to supervariants is the ability of Delta to be transmitted between vaccinated individuals, resulting in sustained infection rates in countries such as the United Kingdom. It’s expensive. “The higher the number of infections per day, the more likely it is that there will be infected patient X, and the immune system is suppressed, so T cells are not strong enough to get rid of the infection,” he says. .. .. “So they will be infected over the days. There is a partial vaccine reaction, the virus learns to avoid them and it leaks, so some antibodies are knocked around. doing.”

Earlier this year, Gupta paper This has shown that this process can occur in critically ill patients who receive convalescent plasma containing antibodies that kill the virus. Their immune system was still unable to get rid of the virus, so it learned to mutate around those antibodies. It is speculated that the widespread use of convalescent plasma in the early stages of the pandemic was responsible for promoting the emergence of mutants.

“I’m not sure, but a lot of plasma is used and it could be one of the variants’ drivers,” he says. “It is very widely used in Brazil, India, the United Kingdom and the United States, all of which have developed their own set of variants.”

Arms race for vaccine variants

Epidemiologists are now trying to model what the new super variant will look like. So far, the major changes in the virus have helped to increase its infectivity. Hanage explains that one of the reasons the delta mutant had such an effect was that it grew very rapidly in human cells before the immune system was activated.As a result, people infected with Delta carry About 1200 times Compared to the original Sars-CoV-2 strain, there are more virus particles in the nose and symptoms appear 2-3 days earlier.

This is the result of natural selection. Various copies of the virus are constantly being made, but the ones that survive and dominate are more likely to infect new people. However, in countries such as the United Kingdom, where the proportion of unvaccinated populations is declining, this can begin to change. Strains that can evade antibodies are more likely to predominate, and the following supervariants are much more likely to evade at least part of the immune response.

“The strain of virus that ultimately survives and becomes dominant depends on what stage of the pandemic you are in,” says Hanage. “So far, it has been much more important for the virus to effectively infect the remaining pools of unprotected people, but it is expected to change by this time.”

This may sound a little scary, but not all is bad news. Epidemiologists do not expect the new supervariants to make them completely useless, as the Covid-19 vaccine is designed with viral evolution in mind. Therefore, it is highly unlikely that it will lead to a major outbreak like the last two years.

In addition, there is a second generation Covid-19 vaccine that has been developed. Vaccine developer Novavax hopes to get Jab regulatory approval within the next few months, but more vaccines are expected to hit the market between now and 2023. All of these platforms have taken their own steps to combat potential future variants.

According to Karin Jooss, Executive Vice President and Head of R & D at Gritstone, a US pharmaceutical company that holds a second-generation Covid-19 vaccine in Phase I clinical trials, the company has all of the existing Sars-CoV-2. Strains are sequenced to produce a neutralizing antibody response against the area of ​​virus conserved among all these strains.

But epidemiologists also believe that relying solely on vaccines is not enough. Gupta said that even if trying to find a way to live with Covid-19 in the UK, some restrictions would need to be put in place to limit the spread of the virus and reduce the chances of the virus mutating. I am.

“At this point, the number of cases is so large that it is much better to prevent new infections,” says Gupta. “In other words, don’t walk around in crowded places or in unmasked buildings. It’s difficult. Looking at the variants we had, they’re all very advanced. It has emerged in uncontrolled infected countries: India, the United Kingdom and Brazil. There is a reason I have never heard of variants in Singapore or South Korea. “

It’s a philosophy that many of his colleagues agree on. “We want to limit the number of opportunities the virus can roll the dice,” says Hanage. “Natural selection is basically talking about the most creative power we know about solving problems. Great. And that’s why you never bet on it. Viruses have evolved. I expect to continue. “