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https://www.wsj.com/articles/new-omicron-studies-help-explain-why-the-variant-is-mild-but-spreads-fast-11641637803

SCIENCE

New Omicron Studies Help Explain Why the Variant Is

Mild but Spreads Fast
Lab studies and clinical data support early reports about the variant that is responsible for the
dramatic surge in Covid-19 cases

People infected with Omicron are less likely to need hospitalization than those who have the Delta
variant, according to recent studies of clinical data.
PHOTO: ALLISON DINNER/BLOOMBERG NEWS

By
Nidhi Subbaraman
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Jan. 8, 2022 5:30 am ET

The threat posed by the Omicron variant has now come into sharper focus, with recent
clinical data and laboratory studies lending support to early reports suggesting that it is
milder but more transmissible than other variants of the new coronavirus.

“It spreads very, very fast, but it doesn’t appear to have the virulence or machismo to
really pack as much of a wallop as the Alpha or Delta variants,” James Musser, chairman
of Houston Methodist Hospital’s pathology and genomic medicine department and the
leader of a new study of Omicron infections, said of the variant.

Recent laboratory studies suggest that Omicron’s lower virulence may reflect its apparent
tendency to thrive in cells in the upper respiratory tract rather than in the lungs, where
Covid-19 infections can cause potentially fatal breathing problems.
Experiments on human respiratory tissues conducted recently at the University of
Cambridge and the University of Hong Kong showed that Omicron prefers to infect cells in
the bronchi, the tubes that connect the windpipe to the lungs, while the Delta variant
better infects and replicates in lung tissue.

“Lower-airway replication is a pathway or a reason for severe disease, and we may have a
situation where a virus is taking us towards a less severe disease outcome,” said Ravindra
Gupta, a University of Cambridge virologist who was involved in the research.

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Similar results were reported by scientists studying Omicron in mice and hamsters, who
found that the variant tended to infect the animals’ nasal passages while other variants
attacked the lungs. The scientists, who posted their research online Dec. 29 in advance of
peer review, also found that animals infected with Omicron developed less severe illness
than animals infected with earlier variants.

“That suggests that the virus has some inherent difficulty in the animal models going
from the upper airway to the lower airway,” said Michael Diamond, a viral immunologist
at Washington University School of Medicine in St. Louis and one of the scientists who
conducted the research. “Now, whether it’s the same reason that’s happening in humans
or not, we don’t know.”

Dr. Diamond said Omicron was unique among multiple coronavirus variants tested so far
in its tendency to affect hamsters’ upper airways but not their lungs.

The findings align with clinical results reported from South Africa, where Omicron was
first identified in November. “We’re just not seeing patients admitted with Covid
pneumonia and lung complications” that often accompany the most severe cases, said
Waasila Jassat, a public health specialist at the National Institute for Communicable
Diseases in Johannesburg.
Researchers said it is too soon in the current surge to conclude that Omicron is less lethal than other
variants.
PHOTO: JOHN MOORE/GETTY IMAGES

But there are limits to how much we can infer about human disease from experiments on
tissue cultures and lab animals, said Vineet Menachery, a virologist at the University of
Texas Medical Branch. What’s more, he said, “hamster models and mouse models are not
great for assays examining the upper airway” because their lungs more closely resemble
humans’ than their upper airways.

Specific mutations in Omicron’s spike protein, the structure the virus uses to attach to
and enter cells, may help explain why the variant spreads so easily. “If it’s better at
infecting cells, then the expectation is that it’s better at transmission,” Dr. Menachery
said.

Omicron’s spike shares mutations spotted in earlier variants that are known to bind virus
particles more tightly to cells, a process that Dr. Menachery likened to a key fitting a lock.
Omicron also has two mutations, H655Y and P681H, that are known to boost the virus’s
ability to enter cells, Dr. Menachery said.

Despite these recent findings, scientists have yet to answer many questions about
Omicron, which has now caused outbreaks in more than 100 countries.

For example, it isn’t yet clear how the course of symptomatic Omicron infections differs in
unvaccinated people and those who have some immunity from vaccination or prior
infection, though early reports suggest that the infections are milder in people with prior
immunity.

Similarly, researchers said it’s too soon in the current surge to conclude that Omicron is
less lethal than other variants—though scientists said the comparatively low
hospitalization rates and reduced need for breathing support associated with the variant
mean that is likely the case.

“It would be hard to imagine that the death rates won’t also be lower,” said Robert
Wachter, chairman of the department of medicine at the University of California, San
Francisco.

Then there is the matter of to what extent immunity resulting from vaccination or prior
infection explains why Omicron infections seem to cause less severe illness. “It’s hard to
tease that apart,” said Dr. Menachery. “Is it less severe because you’re dealing with a
population that has more immunity? Or is it less severe because the virus itself is less
severe?”

People infected with Omicron are less likely to need hospitalization or intensive care than
those who have the Delta variant, according to recent studies of clinical data by Dr.
Musser and other researchers.

“A case of Omicron compared to a case of Delta in a comparable person, comparable

vaccination status, comparable age and risk factors is on the order of 60% or 70% less
severe,” Dr. Wachter said.

The Omicron variant was first detected by South African scientists in November.
PHOTO: JEROME DELAY/ASSOCIATED PRESS

But public health officials have expressed concern that the sheer volume of Omicron cases
—including first-time infections as well as breakthrough infections among vaccinated
people—could overwhelm U.S. hospitals. On Jan. 6, the U.S. had a seven-day average of
602,547 daily reported infections, according to a Wall Street Journal analysis of Johns
Hopkins University data.
As they learn more about Omicron, doctors and public health officials continue to urge
Americans to get vaccinated and boosted and to continue with masking and social
distancing.

“At least during the surge you’re likely to see hospitalizations go up in absolute numbers,
which is why it’s a public health concern, and requires all of us at least for the next six to
eight weeks to take all the measures we can,” said Nahid Bhadelia, an infectious diseases
physician and director of the Center for Emerging Infectious Diseases Policy and Research
at Boston University.

Write to Nidhi Subbaraman at Nidhi.Subbaraman@wsj.com

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