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What does this mean for unvaccinated people? 

Infections that are novel. Transmission has been increased. Recommendations and regulations for new masks. The Delta variety is fuelling COVID-19 outbreaks across the United States, increasing concerns about the pandemic's future.

The extremely contagious Delta variation was discovered in March in India, and it now accounts for more than 93 percent of all sequenced coronavirus infections in the country.

The Centers for Disease Control and Prevention suggested this week that fully vaccinated people in high transmission areas return to masks in public indoor places, noting evidence that the Delta variant can cause high virus loads in the nostrils and throats of even completely vaccinated people.

While scientists agree that the vaccines continue to provide effective protection against Delta variant infection, particularly against severe disease and death, doubts persist. We're only now learning how the new version spreads so quickly, if it causes more serious illness, and why there are more breakthrough infections as Delta expands.

Nadia Roan, Ph.D., associate professor at UC San Francisco, and associate investigator at the Gladstone Institutes spoke with us about the most recent advances in our understanding of the Delta variation.

What difference does the Delta variation make in terms of infectiousness? How does it manages to do so?

The Delta variation, one of four “variants of concern” that have emerged from SARS-CoV-2, the virus that causes COVID-19, is more than twice as virulent as the original virus and as infectious as chickenpox, according to an internal CDC paper.

It's high infectiousness may be attributed to its capacity to multiply quickly in the body. According to a Chinese study, those infected with the Delta version can carry 1,000 times the viral load of those infected with the original virus. “That's startling to me,” Roan added. That study also discovered that those infected with the Delta variant had detectable virus four days earlier than people infected with the original virus (four days versus six days after exposure), and another investigation discovered that they remain infectious for a longer period of time (18 days versus 13 days).

“Not only is it reproducing more, but it is replicating faster, which is presumably why it is spreading so much more efficiently,” Roan explained.

That efficiency is determined by molecular features. We know that the Delta variety has several alterations, including those in the spike protein that it employs to latch onto and infiltrate cells. A spike protein mutation at the furin cleavage location is particularly noteworthy, according to Roan. This location is critical for “priming,” or activating newly replicated viruses so that they may begin infecting cells. According to unpublished research, the original virus primes approximately 50% of its viruses, whereas the Delta version primes more than 75%.

“That could potentially explain why it can transmit considerably more efficiently and why viral loads are so much larger, while other changes that Delta accrued could also, play a role,” Roan added.

Is the Delta variation associated with a more severe disease? 

There is currently no agreement on whether the Delta variation makes patients sicker. The internal CDC document cited studies from Canada and Singapore (not yet peer-reviewed) that found higher odds of hospitalization and death, as well as a study from Scotland that found a twofold increase in hospitalization risk compared to the Alpha variant, which was the dominant variant in the United States prior to Delta's rise.

This is concerning because the Alpha form has already been shown to induce more severe COVID-19 symptoms than the original virus, according to Roan.

What are breakthrough infections, and do they occur more frequently with the Delta variant?

A breakthrough infection is an infection that occurs in a person who has been fully immunized. They can arise when the body's immune system fails to mount a strong enough reaction to avoid an infection.

Overall, all of the vaccines continue to be highly successful in preventing serious disease and mortality caused by the Delta variety. Various studies, for example, have found that the Pfizer vaccine is 93 to 100 percent effective against hospitalization and death, but only 64 to 88 percent effective against all symptomatic disease.

Unvaccinated persons are still five times more likely to become infected than vaccinated people, and 25 times more likely to be hospitalized, according to a recent examination of breakthrough cases among UCSF employees and staff after Delta's outbreak.

While it is unclear why the Delta variety causes more breakthrough infections, “I would imagine the high viral load is a key part of the equation,” said Roan.

“When you're literally just exposed to so much more virus, there's a bigger likelihood of getting infected, whether you're vaccinated or not,” she explained. “Of sure, vaccination is one of the finest barriers, but it is not a complete barrier to infection.”

Breakthrough infections with the Delta form may have an influence on public health, despite the fact that they are currently rare. The CDC stated that the viral load was indistinguishable between breakthrough infections and cases in unvaccinated individuals in an examination of a recent outbreak in Provincetown, MA, that generated over 450 infections in the state.

“Of course, this was what prompted the CDC's suggestion that everyone, including vaccinated persons, wear masks indoors because the evidence would show that breakthrough infections may potentially transmit the virus,” Roan explained.

Do the breakthrough infections imply that the Delta version is more adept at evading vaccines? How does it accomplish this?

According to Roan, all of the variations thus far are considerably better at evading the immune system's antibody reaction as compared to the original virus. Because neutralizing antibodies recognize and bind to the spike proteins on the virus's surface, they prevent the virus from infecting cells. However, if the virus mutates its spike protein, the antibodies may not bind as strongly, giving the virus an advantage.

“The good news is that the vaccinations were intended to protect against severe COVID and are still working”.

Fortunately, the antibody reaction is only part of the picture, according to Roan, whose team examines the T cell response, another component of our immune system. She and her colleagues discovered evidence that genetic differences have less of an impact on our T cell response.

“T cells operate in a unique manner,” she explains. T cells do not directly target the virus, but rather recognize infected cells and destroy them, preventing the virus from reproducing inside them. Recognition can also activate "helper" T cells, which help other immune cells respond. An infected cell communicates with a T cell by displaying small bits of viral protein on its surface.

“The T cells are more resistant to the mutational effect because each person exposes a different tiny portion of the virus to their T cells,” Roan explained. As a result, a mutation would primarily impact people whose cells contain that specific component of the virus. “When the virus is transmitted to another person, that mutational advantage is gone, unlike in the case of antibodies, where neutralizing antibodies from different individuals frequently target the same sites in the spike protein.”

“In other words, as the virus mutates, antibodies are less able to execute their job, but T cells are more resistant to the mutation effects,” Roan explained.

How critical is our T cell response in combating the Delta variant?

Nadia Roan's photo Nadia Roan is a PhD candidate.

Roan's group is already planning to analyze the Delta version, and she is certain that the T cell response will be sustained. They've already demonstrated that the T cell response to the Alpha, Beta, and Gamma versions is just as robust as it is to the original virus.

Roan's team has also discovered that T cells may play a critical role in avoiding severe COVID-19 infections. In a study of COVID-19 patients in the ICU, those who recovered exhibited a large increase in T cell response just before being discharged from the hospital, whereas those who died never developed

“T cells are probably less critical for avoiding that first infection - that's where neutralizing antibodies come in,” Roan explained. “However, T cells play an essential role in ensuring that someone who has already been infected recovers.”

What does Does the Delta variation means for unvaccinated people? For folks who have had all of their vaccinations?

The Delta strain poses a major threat to the unprotected, and it is, therefore, more important than ever to get vaccinated. “It's absolutely going to be riskier,” Roan said. “Right now, as many people have stated, there is a pandemic of unvaccinated people in this country.” Currently, more than 97 percent of people hospitalized with severe COVID-19 are unvaccinated.

According to Roan, the faster we can get more people vaccinated, the faster we can recover from the present surges, minimize deaths, and prevent stressing the medical system.

While breakthrough infections are more common with the Delta variation, they are usually minor or asymptomatic. “The good news is that the immunizations were designed to protect against severe COVID, and they are still working,” Roan added.

Returning to indoor masks serve two goals for persons who are properly vaccinated, according to Roan. First, because fully vaccinated people can still carry high viral loads and transmit the virus, masking protects those who are not vaccinated, including children under the age of 12, as well as vaccinated individuals who may have weaker immune responses to the vaccine, such as immunocompromised people. The second reason is that we still don't know what the risk of long-term COVID-19 infection after a breakthrough infection is. “That's all unknown right now,” Roan explained, “so I think it's prudent to wear a mask.”

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