strain of the virus—between 20% and 30%,
the researchers estimate. That’s much less
than the drop in antibody efficacy. “T cells
are holding out against Omicron,” Burgers
concludes. “And the data is very consistent
across vaccines.”
That may help explain South Africa’s low
hospital burden, Burgers says. “Of course
it could be other things about the biology
of this variant,” she adds, “but certainly
from everything we know about T cells,
this is what they do—control a virus once
you’ve been infected. So this is their time
to shine.”
MEANWHILE, RESEARCHERS studying Omi-
cron’s behavior in the lab are turning up
surprises. “There is something very weird
about this virus,” Peacock says. Normally,
SARS-CoV-2 replicates well in Vero cells—
kidney cells from African green monkeys—
genetically engineered to be studded with
the virus’ receptors, ACE2 and TMPRSS2.
With any previous strain, such infections
lead to visible areas of damage in the cell
culture called plaques. But that’s happening
much less with Omicron, Peacock says. “It’s
not liking the cell lines that have been our
bread and butter all the way through.”
Researchers in Hong Kong have seen
notable differences in another system, in
which the virus infects healthy lung tissue
taken from lung cancer patients during sur-
gery. Omicron replicates much faster than
previous variants in cells from the bronchi,
but much slower in cells from lower in the
lungs. “Whilst the other strains take off
after about 72 hours in the bronchus, this
one goes up within 24 hours,” says John
Nicholls, a pathologist at the University of
Hong Kong. The data, published in a short
note online and submitted to a journal,
might explain why Omicron spreads better
while perhaps causing less severe disease.
Virus in the bronchi is more likely to be ex-
haled, whereas deep in the lung it is likely
to cause more severe disease. But Nicholls
urges caution in interpreting the data.
“We’re being very, very careful,” he says.
Some of Omicron’s many mutations
initially didn’t bode well. Scientists have
zeroed in on changes close to the furin
cleavage site, a motif in the spike protein
that allows it to be more easily cleaved,
which is an important step in the infec-
tion of a human cell. Mutations around this
site appear to have made both Alpha and
Delta more transmissible and better at in-
fecting cells. Omicron carries the mutation
Alpha had, P681H, and another one close by
called N679K. “Just from sequence gazing,
we thought, this is probably going to have
Delta-like transmissibility and pathogenic-
ity,” Peacock says.
But a preprint by virologist Ravi Gupta
of the University of Cambridge suggests
the opposite could be true: Using viruses
modified to carry the spike protein of Omi-
cron and other variants, they found that
Omicron’s spike is cleaved much less effi-
ciently than Alpha’s or Delta’s. That could
explain why Omicron might be worse at in-
fecting certain cells than previous variants.
His preprint also suggests another con-
trast. Research on previous variants has
suggested SARS-CoV-2 can cause neighbor-
ing cells to merge into syncytia, large cells
with multiple nuclei. Syncytia have been
found in the lungs of patients who died of
COVID-19 and may be related to disease se-
verity, Gupta says. Kei Sato, a virologist at
the University of Tokyo, has shown that the
more pathogenic Delta variant was more
likely to cause syncytia in cell culture. Now,
Sato and Gupta both have data suggesting
syncytia may be rarer with Omicron. Tak-
ing all of the data together, Gupta says, “I
think the evidence is mounting ... that the
virus potentially causes less progression to
severe disease.”
The role of syncytia is far from clear,
however. SARS-CoV, the virus that causes
severe acute respiratory syndrome, has not
been shown to cause them. And although
SARS-CoV-2 seems to trigger syncytia in
cell culture, they don’t appear in animal
models, Nicholls says: “In the hamsters we
looked at, in the mice we looked at, you
don’ t get the syncytia.” Christian Drosten, a
virologist at Charité University Hospital in
Berlin, says syncytia in COVID-19 patients
may have other explanations, such as the
reactivation of herpes infections, which
are known to cause syncytia formation.P E ACO C K SAYS it’s simply too early to draw
firm conclusions from the lab studies. “I
think there’s definitely something interest-
ing going on there. But I wouldn’t like to
bet that other people are definitely going
to find the exact same thing,” he says. Gary
Whittaker, a virologist at Cornell University,
says Omicron seems to behave more like
seasonal coronaviruses, which are often
hard to grow in cell culture. That makes ex-
periments on the new variant even harder
to interpret, he says. “We’ve got to get a sys-
tem which is much better matched to the
virus, otherwise we will very easily get led
astray if we’re not careful.”
Getting firm answers from the lab may
well take until Easter, Drosten says. By
that time, the world may have learned how
much severe disease the variant causes the
hard way. “So far, variants that replicate
more have caused more disease,” Drosten
says. “So we would do well to be very care-
ful with this variant.” j1544 24 DECEMBER 2021 • VOL 374 ISSUE 6575 science.org SCIENCENEWS | IN DEPTH
B
arely a year after vaccine develop-
ers reported spectacular successes
against SARS-CoV-2, the latest vari-
ant of the virus has presented them
with a new challenge. Omicron is
spreading at unprecedented speed,
and studies of blood samples and emerging
real-world evidence show one reason is its
ability to dodge immunity, whether from
previous infections or vaccination. The new
threat has galvanized vaccine developers
and public health officials—but they are not
all pushing in the same direction.
Reacting to evidence that an additional
dose can restore some protection against
Omicron, many countries are racing to give
booster shots of existing vaccines. Some
scientists think that is unnecessary, argu-
ing two doses of the current messenger
RNA (mRNA) vaccines may not prevent in-
fections but will suffice to keep most people
who are otherwise healthy from getting se-
riously sick with COVID-19. Others think it’s
time for revised vaccines. A booster tailored
to Omicron would likely offer better protec-
tion, says vaccinologist Florian Krammer
of the Icahn School of Medicine at Mount
Sinai. Vaccine manufacturers, eyeing a new
market, are doing the preliminary work to
concoct new formulations.
Rather than chasing SARS-CoV-2 vari-
ants with tailored shots, another camp says
it’s better to push for universal vaccines
that protect against all SARS-CoV-2 mu-
tants, as well as other coronaviruses that
nature throws at humans. Because of Omi-
cron, “There is even stronger interest in our
approach,” says Kayvon Modjarrad of the
Walter Reed Army Institute of Research,
who is developing a pancoronavirus vac-
cine candidate that has just completed a
phase 1 trial. Other pancoronavirus candi-
dates may start trials in 2022.
The dramatic rise of the Omicron vari-By Jon CohenCOVID-Omicron sparks
a vaccine
strategy debate
Current boosters,
variant-specific shots,
and universal coronavirus
vaccines all have fans