New Omicron studies help explain why the variant is mild but spreads quickly

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

“It spreads very, very quickly, but it doesn’t seem to have the virulence or the machismo to really cause as much of a stir as the Alpha or Delta variants,” James Musser, chair of the Houston Methodist Department of Pathology and Genomic Medicine Hospital and the leader of a new study of Omicron infections, said about the variant.

Recent lab studies suggest that Omicron’s lower virulence may reflect its apparent tendency to thrive in cells in the upper respiratory tract rather than the lungs, where Covid-19 infections can cause potentially fatal respiratory problems.

Experiments on human respiratory tissues recently conducted 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 trachea to the lungs, while the Delta variant infects and replicates better in lung tissue.

“Lower respiratory tract replication is a pathway or cause for serious illness, and we could have a situation where a virus leads us to a less serious illness outcome,” said Ravindra Gupta, a University of Cambridge virologist who was involved. during the investigation. .

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Similar results were reported by scientists who studied Omicron in mice and hamsters, who found that the variant infected the nasal passages of the animals, while other variants affected the lungs. The scientists, who posted their study online on Dec. 29 prior to peer review, also found that animals infected with Omicron developed less severe disease than animals infected with earlier variants.

“That suggests that the virus has inherent problems with the animal models that move from the upper respiratory tract to the lower respiratory tract,” said Michael Diamond, a viral immunologist at Washington University School of Medicine in St. Louis and one of the scientists who conducted the research. . “Whether it’s the same reason that happens in humans or not, we don’t know.”

dr. Diamond said Omicron was unique among several coronavirus variants tested so far because it affects hamsters’ upper respiratory tract, but not their lungs.

The findings are consistent with clinical results reported from South Africa, where Omicron was first identified in November. “We just don’t see patients being 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 of Communicable Diseases in Johannesburg.

Researchers said it’s too early to conclude that Omicron is less lethal than other variants.


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John Moore/Getty Images

But there are limits to how much we can deduce about human disease from tissue culture and laboratory animal experiments, said Vineet Menachery, a virologist at the University of Texas Medical Branch. In addition, he said, “hamster models and mouse models aren’t great for tests examining the upper airways,” because their lungs are more like humans than their upper airways.

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

The peak of Omicron shares mutations noted in previous variants that are known to bind virus particles more tightly to cells, a process Dr. Menachery compared it to a key that fits in a lock. Omicron also has two mutations, H655Y and P681H, which are known to enhance the virus’s ability to enter cells, said Dr. menachery.

Scientists are using automation, real-time analysis and pooling data from around the world to quickly identify and understand new coronavirus variants before the next one spreads widely. Photo illustration: Sharon Shi

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 is not yet clear how the course of symptomatic Omicron infections differs in unvaccinated people and those who have some immunity to vaccination or previous infections, although early reports suggest the infections are milder in people with previous immunity.

Likewise, researchers said it’s too early in the current wave to conclude that Omicron is less lethal than other variants, although scientists said the relatively low hospitalizations and reduced need for respiratory support associated with the variant mean it likely is.

“It’s hard to imagine that death rates won’t be lower as well,” said Robert Wachter, chair of the division of medicine at the University of California, San Francisco.

Then there is the question of how far immunity due to vaccination or previous infection explains why Omicron infections appear to cause less serious illness. “It’s hard to tell that apart,” said Dr. menachery. “Is it less severe because you’re dealing with a population that has more immunity? Or is it less serious because the virus itself is less serious?”

People infected with Omicron are less likely to require 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 individual, vaccination status, age and risk factors is on the order of 60% or 70% less severe,” said Dr. watchman.

The Omicron variant was first discovered by South African scientists in November.


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Jerome Delay/Associated Press

But public health officials have expressed concern that the sheer number of Omicron cases — including first-time infections and breakthrough infections among vaccinated people — could overwhelm US hospitals. As of Jan. 6, the U.S. had a seven-day average of 602,547 daily reported infections, according to a Wall Street Journal analysis of data from Johns Hopkins University.

As they learn more about Omicron, doctors and public health officials continue to urge Americans to get vaccinated and encouraged and to continue masking and social distancing.

“During the wave surge, you will probably see hospital admissions increase in absolute numbers, therefore it is a public health concern, and it will require all of us to take all the measures we can over the next six to eight weeks,” said Nahid Bhadelia, infectious disease 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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