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Some COVID-19 Survivors May Be Better Protected From Variants Than Others

transmission electron microscope image shows SARS-CoV-2
Transmission electron microscope image of SARS-CoV-2. | NIAID

Vaccinated individuals and those who recovered from severe COVID-19 may be
at lower risk for subsequent severe infections with SARS-CoV-2 variants
than people who had milder cases, according to a new study in
the September 3 issue of Science Advances.

The analysis, which included blood serum samples from 69 COVID-19 patients
and 50 fully vaccinated healthcare workers in the Netherlands, found that
serum from all study subjects showed a reduced response to the alpha, beta,
and gamma variants compared to the original strain.

While serum from vaccinated individuals and those with severe enough
COVID-19 to require hospitalization still induced adequate antibody
responses, serum from patients with mild COVID-19 infections showed lower
antibody responses to the original virus. Serum from these mild COVID-19
patients also often showed no response to the beta and gamma variants.

"We were surprised at how well the vaccine studied here recognizes all
variants of concern — that's really a testament to how well the SARS-CoV-2
vaccines work," said Tom Caniels, a Ph.D. student at Amsterdam University
Medical Centers (UMC) and one of the first authors of the study.

People who have not been vaccinated and are relying on antibody protection
from a mild case of COVID-19, however, may be treading on thin ice.

"The main message to people that have had mild COVID-19 but are debating
whether to take a shot is quite simple: get a vaccine," said Caniels. "We
clearly show that these people have lower levels of antibodies than those
who are severely ill or those who are vaccinated. Sometimes, lower antibody
levels translate into an inability to recognize viral variants."

While the study was conducted before the delta variant became the dominant
strain worldwide, Caniels and colleagues are currently extending their
investigation to assess this variant.

"We have some preliminary data on multiple different vaccines, and it seems
that delta does not impact the antibody titers elicited by vaccination more
than any of the variants studied here," said Caniels. "The current vaccines
do a very good job of protecting against delta."

Do Variants Threaten Immunity?

The researchers began the study in late 2020, when the alpha variant
(B.1.1.7) was circulating widely around the world, beta (B.1.351) was on
the rise in South Africa, and gamma (B.1.1.28.P1) was raising concerns in
Brazil. Disturbed by mutations in the viral spike protein in beta and
gamma, which had been found to reduce antibodies' abilities to fend off the
viral invaders, Caniels and colleagues decided to investigate whether the
subtle genetic changes in these rapidly spreading variants could threaten
immunity conferred by vaccination or previous infection.

"When we initiated the study, there was not yet a complete overview with
multiple variants of concern," said Caniels. "Most other studies focused on
either one variant of concern or one study group, meaning only infected
individuals or only vaccinated individuals."

To uncover just how much of a hazard these variants posed to the previously
infected or vaccinated, the researchers assessed serum from 28 hospitalized
and 41 non-hospitalized COVID-19 patients in the Netherlands, who were
sampled four to six weeks after symptom onset between March 2020 and
January 2021, as well as serum from 50 health care workers who had received
two doses of the Pfizer vaccine.

Beta Proves Evasive

When Caniels and colleagues tested how well neutralizing antibodies in
serum from each group defended against each SARS-CoV-2 variant, they found
the largest decrease in antibodies' ability to recognize the beta variant,
particularly among patients with mild COVID-19. 39% of these
non-hospitalized patients had lost all ability to neutralize beta, while
34% could not neutralize gamma at detectable levels. Serum from these
patients could, however, still neutralize the alpha variant and a
SARS-CoV-2 pseudovirus (which, unlike a live virus, cannot replicate).

All of the hospitalized patients still showed at least some ability to
neutralize all three variants, and only one of the vaccine recipients lost
its neutralizing activity against beta.

"The beta variant has some mutations in its spike protein that are also
found in other strains," said Caniels. "If these strains remain dominant
across the globe and amass more mutations, cases of breakthrough infection
will occur."

Caniels suggests that if strains of the virus with spike proteins that
differ greatly from the one currently present in COVID-19 vaccines continue
to emerge and spread, it may eventually be wise to introduce an updated
vaccine. However, he does not think the time has come for a modified
vaccine designed to increase immune coverage.

"For now, two shots of the vaccine studied here protect very well and
induce very good immune responses against many different variants of
concern," said Caniels.


Shannon Kelleher

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