In studies on mice and hamsters, omicron
produced less-damaging infections, often limited largely to the upper airway:
the nose, throat and windpipe. The variant did much less harm to the lungs,
where previous variants would often cause scarring and serious breathing
difficulty.
“It’s fair to say that the idea of a disease that manifests itself primarily in
the upper respiratory system is emerging,” said Roland Eils, a computational
biologist at the Berlin Institute of Health, who has studied how coronaviruses infect
the airway.
In November, when the first report on
the omicron variant came out of South Africa, scientists could only guess at
how it might behave differently from earlier forms of the virus. All they knew
was that it had a distinctive and alarming combination of more than 50 genetic
mutations.
Previous research had shown that some of
these mutations enabled coronaviruses to grab onto cells more tightly. Others
allowed the virus to evade antibodies, which serve as an early line of defence
against infection. But how the new variant might behave inside of the body was
a mystery.
“You can’t predict the behaviour of
virus from just the mutations,” said Ravindra Gupta, a virus expert at the
University of Cambridge.
Over the past month, more than a dozen
research groups, including Gupta’s, have been observing the new pathogen in the
lab, infecting cells in petri dishes with omicron and spraying the virus into
the noses of animals.
As they worked, omicron surged across
the planet, readily infecting even people who were vaccinated or had recovered
from infections.
But as cases skyrocketed,
hospitalisations increased only modestly. Early studies of patients suggested
that omicron was less likely to cause severe illness than other variants,
especially in vaccinated people. Still, those findings came with a lot of
caveats.
For one thing, the bulk of early omicron
infections were in young people, who are less likely to get seriously ill with
all versions of the virus. And many of those early cases were happening in
people with some immunity from previous infections or vaccines. It was unclear
whether omicron would also prove less severe in an unvaccinated older person,
for example.
Experiments on animals can help clear up
these ambiguities, because scientists can test omicron on identical animals
living in identical conditions. More than a half-dozen experiments made public
in recent days all pointed to the same conclusion: Omicron is milder than delta
and other earlier versions of the virus.
On Wednesday, a large consortium of
Japanese and American scientists released a report on hamsters and mice that
had been infected with either omicron or one of several earlier variants. Those
infected with omicron had less lung damage, lost less weight and were less likely
to die, the study found.
Although the animals infected with
omicron on average experienced much milder symptoms, the scientists were
particularly struck by the results in Syrian hamsters, a species known to get
severely ill with all previous versions of the virus.
“This was surprising, since every other
variant has robustly infected these hamsters,” said Dr. Michael Diamond, a
virus expert at Washington University and a co-author of the study.
Several other studies on mice and
hamsters have reached the same conclusion. (Like most urgent omicron research,
these studies have been posted online but have not yet been published in
scientific journals.)
The reason that omicron is milder may be
a matter of anatomy. Diamond and his colleagues found that the level of omicron
in the noses of the hamsters was the same as in animals infected with an
earlier form of the coronavirus. But omicron levels in the lungs were one-tenth
or less of the level of other variants.
A similar finding came from researchers
at the University of Hong Kong who studied bits of tissue taken from human
airways during surgery. In 12 lung samples, the researchers found that omicron
grew more slowly than delta and other variants did.
The researchers also infected tissue
from the bronchi, the tubes in the upper chest that deliver air from the
windpipe to the lungs. And inside of those bronchial cells, in the first two
days after an infection, omicron grew faster than delta or the original
coronavirus did.
These findings will have to be followed
up with further studies, such as experiments with monkeys or examination of the
airways of people infected with omicron. If the results hold up to scrutiny,
they might explain why people infected with omicron seem less likely to be
hospitalised than those with delta.
Coronavirus infections start in the nose
or possibly the mouth and spread down the throat. Mild infections do not get
much further than that. But when the coronavirus reaches the lungs, it can do
serious damage.
Immune cells in the lungs can overreact,
killing off not just infected cells but uninfected ones. They can produce
runaway inflammation, scarring the lung’s delicate walls. What’s more, the
viruses can escape from the damaged lungs into the bloodstream, triggering
clots and ravaging other organs.
Gupta suspects that his team’s new data
give a molecular explanation for why omicron does not fare so well in the
lungs.
Many cells in the lung carry a protein
called TMPRSS2 on their surface that can inadvertently help passing viruses
gain entry to the cell. But Gupta’s team found that this protein does not grab
on to omicron very well. As a result, omicron does a worse job of infecting
cells in this manner than delta does. A team at the University of Glasgow
independently came to the same conclusion.
Through an alternative route,
coronaviruses can also slip into cells that do not make TMPRSS2. Higher in the
airway, cells tend not to carry the protein, which might explain the evidence
that omicron is found there more often than the lungs.
Gupta speculated that omicron evolved
into an upper-airway specialist, thriving in the throat and nose. If that is
true, the virus might have a better chance of getting expelled in tiny drops
into the surrounding air and encountering new hosts.
“It’s all about what happens in the
upper airway for it to transmit, right?” he said. “It’s not really what happens
down below in the lungs, where the severe disease stuff happens. So you can
understand why the virus has evolved in this way.”
While these studies clearly help explain
why omicron causes milder disease, they do not yet answer why the variant is so
good at spreading from one person to another. The United States logged more
than 580,000 cases on Thursday alone, the majority of which are thought to be
omicron.
“These studies address the question
about what may happen in the lungs but don’t really address the question of
transmissibility,” said Sara Cherry, a virus expert at the Perelman School of
Medicine at the University of Pennsylvania.
Diamond said he wanted to wait for more
studies to be carried out, especially in people instead of animals, before
endorsing the hypothesis that TMPRSS2 is the key to understanding omicron. “I
think it is still premature on this,” he said.
Scientists know that part of omicron’s
contagiousness comes from its ability to evade antibodies, allowing it to
easily get into cells of vaccinated people far more easily than other variants.
But they suspect that omicron has some other biological advantages as well.
Last week, researchers reported that the
variant carries a mutation that may weaken so-called innate immunity, a
molecular alarm that rapidly activates our immune system at the first sign of
an invasion in the nose. But it will take more experiments to see if this is
indeed one of omicron’s secrets to success.
“It could be as simple as, this is a lot
more virus in people’s saliva and nasal passages,” Cherry said. But there could
be other explanations for its efficient spread: It could be more stable in the
air or better infect new hosts. “I think it’s really an important question,”
she said.
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