This is how the mysterious mutations that make the delta variant so dangerous work. And it's going to get worse

By Liz Szabo - Kaiser Health News

At first glance, mutations in the highly contagious delta variant of COVID-19 don't seem as worrisome.

For starters, it has fewer genetic changes than previous coronavirus mutations.

"When it became known that the epidemic in India was delta-driven, no one imagined that it would be as bad or that it would outperform other variants," said Trevor Bedford, a biologist at the Fred Hutchinson Center for Cancer Research.

They were wrong.

Delta has kept some of the most successful mutations found in previous variants, but it also contains new genetic changes that allow it to spread twice as fast.

Delta is more dangerous in many ways.

It has an incubation period of four days, instead of six, which makes people catch it sooner.

When the pandemic started, people were infecting an average of two to three people.

Today there are, on average, six.

As of the middle of this week, the delta variant had caused at least 92% of new infections in the United States, according to covariants.org, a Swiss research company.

Although the delta variant is not necessarily more deadly than others, it can kill large numbers of people simply because it infects many more, said Dr. Eric Topol, founder and director of the Scripps Research Translational Institute.

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Scientists have sequenced the delta mutations but are still trying to understand their relevance, said Angela Rasmussen, a virologist with the University of Saskatchewan Vaccine and Infectious Diseases Organization.

"When we see that the same mutations appear repeatedly and independently, that suggests they are important," Rasmussen said.

Scientists know best about mutations in the so-called spike (or spike) protein, which protrudes from the virus's surface like a club, and has been studied most intensively for its serious ramifications, Rasmussen explained.

The coronavirus uses the spike protein to enter human cells, and its changes can help the virus evade antibodies.

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Scientists believe that one of the most important areas of this peak is the receptor-binding region (RBD), the specific part of the protein that allows the virus to latch onto a receptor on the surface of our cells, said Vaughn Cooper, professor. of Microbiology and Molecular Genetics from the University of Pittsburgh.

Receptors are like sockets or docking stations that allow proteins to interact with the cell.

Once the virus enters the cell, it can wreak havoc, hijacking the genetic machinery and turning it into a virus factory.

The worrying delta mix

Delta's rapid spread is surprising, since it lacks the two mutations that made the earlier variants so fearsome.

Delta does not have the N501Y mutation found in alpha, beta, and gamma variants, which allowed them to invade cells more successfully than the parent virus.

That mutation changed an amino acid - a building block of proteins - in RBD, the virus's receptor that helps it penetrate the cell.

Delta also lacks the E484K mutation, which has made the gamma variant so worrisome.

This genetic change, sometimes called Eek, allows the virus to spread even between vaccinated people.

Scientists use the Greek alphabet to name the variants that are of most concern.

"The 'D' in delta stands for 'different' and a 'detour' to a different genomic mutation pathway," Topol said.

"But it doesn't mean 'destruction,'" he added, noting that existing COVID-19 vaccines are still effective.

Vaccines protect people from the coronavirus by providing them with antibodies that stick to the spike protein, preventing the virus from entering cells.

By dramatically reducing the number of viruses that enter cells, vaccines can prevent people from developing serious disease, and it also makes them less infectious.

Delta is more dangerous in many ways.

It has an incubation period of four days, instead of six, which makes people catch it sooner.

Delta shares mutations with other successful variants.

Like all identified strains, delta contains a spike mutation called D614G, sometimes known as Doug, which became ubiquitous last year.

Scientists believe that Doug increases the density of the peak protein on the surface of the virus particles and facilitates the entry of the virus into cells.

Delta also has a spike mutation called P681R, which closely resembles an alpha variant mutation that would produce higher viral loads in patients, according to Cooper.

People infected with delta have 1,000 times more viruses in their airways, making them more likely to spread the virus when they sneeze, cough, or speak.

The P681R mutation, which is also found in the kappa variant, is located early in a part of the genome called the furin cleavage site, Cooper explained.

Furin is a natural human enzyme that the coronavirus hijacks: it uses it to cut the spike protein in an optimal way to enter the cell, Rasmussen said, noting that the new mutation makes that work more efficient.

Another delta mutation, which is also found in kappa and epsilon, is called L452R.

Experiments suggest that this mutation, which also affects RBD, works by preventing antibodies from neutralizing the virus, Cooper explained.

These mutations appear to be more formidable as a team than individually.

The genetic changes "certainly do something, but it's not entirely clear why that combination makes the delta variant more suitable," Bedford said.

"Getting together seems to be the key."

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Delta has also developed genetic changes that are not seen in other variants.

One of those peak mutations is D950N.

"This may be different," Cooper said.

"We don't see it anywhere else," he added.

Cooper explained that the D950N mutation is different because it is located outside the receptor-binding region, in an area of ​​the coronavirus genome that helps it fuse with human cells.

This fusion allows the coronavirus to shed its genetic material into those cells.

This mutation could affect the types of cells that the virus infects, allowing it to damage different organs and tissues.

Mutations in this region are also associated with a higher viral load, Cooper said.

Delta also contains mutations in a part of the spike protein called the N-terminal domain, which provides a supersite for antibodies to adhere to the virus and prevent its entry into cells, said Dr. Hana Akselrod, an infectious disease specialist at the School. of Medicine and Health Sciences from George Washington University.

Mutations in this region make monoclonal antibodies less effective in treating COVID-19, and increase the ability of the delta variant to escape antibodies generated by the vaccine, Akselrod noted.

This could explain why vaccinated people are slightly more likely to be infected with delta, which causes mild illness, but allows them to spread the virus.

The future behavior of delta

Scientists say it is impossible to predict exactly how delta will behave in the future, although Topol said: "It will get worse."

Topol noted that delta outbreaks typically last 10-12 weeks as the virus "rampages" among susceptible populations.

If the United States follows the pattern seen in the United Kingdom and the Netherlands, infections could rise from the current seven-day moving average of 42,000 cases to 250,000 a day.

However, Topol noted that the United States is unlikely to suffer from the high death rates seen in India, Tunisia and Indonesia because nearly half of the population is fully vaccinated.

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While some studies have concluded that the Johnson & Johnson vaccine stimulates strong and persistent antibodies against delta, a new report found that the antibodies raised by a single injection may not be enough to neutralize it.

The authors of that study, from New York University's Grossman School of Medicine, suggested that a second dose might be necessary.

Two doses of the Pfizer-BioNTech vaccine protect 94% of people from any symptomatic infection with the alpha variant, compared with 88% against the delta variant, according to a new study published in the New England Journal of Medicine.

Two doses of AstraZeneca vaccine protect 75% of people from the alpha variant and 67% from delta.

Cooper said COVID-19 vaccines offer remarkable protection.

"I will always celebrate these vaccines as one of the scientific achievements of my time," he remarked.

The best way to slow the evolution of variants is to share vaccines with the world, vaccinating as many people as possible, Bedford stressed.

Because viruses only undergo genetic changes when they spread from one host to another, stopping transmission denies them the opportunity to mutate.

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Whether the coronavirus develops more deadly variants "is entirely in our hands," Cooper said.

"If the number of infections remains high, it will continue to evolve."

By not containing the virus through vaccination, wearing face masks and avoiding crowds, you are allowing the coronavirus to transform into increasingly dangerous forms, warned Dr. William Haseltine, a former Harvard Medical School professor who helped to design treatments for HIV / AIDS.

"It's getting better, and we're doing better," he said, "having half the population vaccinated and the other half unvaccinated and unprotected: that's the experiment I would do if I were a demon and tried to design a virus that destroys vaccines".

KHN (Kaiser Health News) is the newsroom of KFF (Kaiser Family Foundation), which produces in-depth journalism on health issues. Along with Policy Analysis and Surveys, KHN is one of KFF's top three programs. KFF is a nonprofit organization that provides health information to the nation.