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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