Omicron Doesn’t Affect the Lungs So Well, Animal Studies Find

A series of recent studies in laboratory animals and human tissues provide the first clues as to why the Omicron variant causes milder illness than previous versions of the coronavirus.

In studies on mice and hamsters, Omicron produced less harmful infections that are usually largely confined to the upper respiratory tract: the nose, throat, and trachea. The variant did much less damage to the lungs, where previous variants often caused scarring and severe breathing difficulties.

Roland Eils, a computer biologist at the Berlin Institute of Health, said: “It would be fair to say that the idea of ​​a disease that manifests itself primarily in the upper respiratory system arose.” studied How coronaviruses infect the airway.

First report in November. Omicron variant Because it originated in South Africa, scientists could only guess at how the virus might behave differently from previous forms. All they knew was that he had a distinctive and alarming combination of more than 50 genetic mutations.

Previous research has shown that some of these mutations enable coronaviruses to attach more firmly to cells. Others allowed the virus to evade antibodies that acted as an early line of defense against infection. But how the new variant might behave inside the body was a mystery.

“You can’t predict the behavior of the virus from mutations alone,” said Ravindra Gupta, a virologist at the University of Cambridge.

Within the past month, Dr. More than a dozen research groups, including Gupta, observed the new pathogen in the lab, infecting cells in Petri dishes with Omicron, and spraying the virus into the animals’ noses.

As they worked, Omicron spread all over the planet, easily infecting even people who had been vaccinated or recovered from the infection.

But as cases skyrocketed, hospitalizations increased only modestly. Initial studies in patients suggested that Omicron was less likely to cause serious illness than other variants, especially in people who were vaccinated. Still, these findings came with many caveats.

First, the bulk of early Omicron infections were in young people who were less likely to become seriously ill with all versions of the virus. And most of these early cases were in people who had some immunity from previous infections or vaccines. For example, it was unclear whether Omicron would be less severe in an unvaccinated elderly person.

Experiments on animals can help clear up these uncertainties, because scientists can test the Omicron on identical animals living in the same conditions. More than half a dozen experiments that have been made public in recent days have pointed to the same conclusion: Omicron is milder than Delta and other previous versions of the virus.

On Wednesday, a large consortium of Japanese and American scientists statement On hamsters and mice infected with Omicron or one of several earlier variants. The study found that those infected with Omicron had less lung damage, lost less weight, and were less likely to die.

Although animals infected with Omicron experienced much milder symptoms on average, scientists were particularly impressed with the results in Syrian hamsters, a species known to have been seriously ill with all previous versions of the virus.

A virologist at the University of Washington and co-author of the study, Dr. “This was surprising because all the other variants strongly infected these hamsters,” said Michael Diamond.

A few other studies on mice and hamster have come to the same conclusion. (Like the most urgent Omicron research, these studies have been published online, but not yet in scientific journals.)

The reason the Omicron is lighter may be a matter of anatomy. Dr. Diamond and colleagues found that the level of Omicron in the noses of hamsters is the same as in animals infected with an earlier form of the coronavirus. Omicron levels in the lungs, however, were one-tenth or less that of the other variants.

A similar finding It came from researchers at the University of Hong Kong who studied pieces 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.

The researchers also infected tissues from the bronchi, which are tubes in the upper chest that carry air from the windpipe to the lungs. And inside these bronchial cells, in the first two days after an infection, Omicron grew faster than Delta or the original coronavirus.

These findings will need to be followed up with further studies, such as experiments with monkeys or examination of the respiratory tracts of people infected with Omicron. If the results are based on scrutiny, they may explain why people infected with Omicron seem less likely to be hospitalized than those with Delta.

Coronavirus infections start in the nose or possibly the nose. mouth and spread to the throat. Mild infections don’t go any further than that. However, when the coronavirus reaches the lungs, it can cause serious damage.

Immune cells in the lungs can overreact, killing not only infected cells but also uninfected ones. They can produce runaway inflammation by injuring the delicate walls of the lung. What’s more, viruses can escape from damaged lungs into the bloodstream, triggering clots and destroying other organs.

Dr. Gupta suspects his team’s new data offers a molecular explanation for why the Omicron isn’t performing so well in the lungs.

Many cells in the lung carry a protein called TMPRSS2, which can help viruses that accidentally pass on their surface enter the cell. However, Dr. Gupta’s team found that this protein does not grasp Omicron very well. As a result, Omicron does a worse job than Delta at infecting cells this way. A team at Glasgow University independently came to the same conclusion.

In an alternative route, coronaviruses can also enter cells that do not make TMPRSS2. Cells higher up in the airway tend not to carry the protein; this may explain the evidence that Omicron is more commonly found in the lungs.

Dr. Gupta speculated that Omicron had developed into an upper respiratory specialist who thrived on the throat and nose. If this is true, the virus may have a higher chance of being shed in small droplets into the surrounding air and encountering new hosts.

“It’s all about what happens to transmit in the upper respiratory tract, right?” said. “Actually, it’s not what’s down there in the lungs where serious disease events happen. So you can understand why the virus is evolving that way.”

While these studies help clearly explain why Omicron causes milder disease, they do not yet answer why the variant is so good at spreading from one person to another. USA signed in more than 580,000 cases On Thursday alone, the majority are thought to be Omicron.

“These studies address the question of what might happen in the lungs, but they don’t really address the issue of contagiousness,” he said. Sara Cherry, a virologist at the University of Pennsylvania Perelman School of Medicine.

Dr. Diamond said he wants to wait for more studies to be done, specifically in humans rather than animals, before confirming the hypothesis that TMPRSS2 is the key to understanding Omicron. “I think it’s still early on that,” he said.

Scientists know that part of Omicron’s infectivity comes from its ability to evade antibodies, allowing it to enter the cells of vaccinated people much more easily than other variants. But they suspect Omicron has other biological advantages as well.

Researchers last week reported A molecular alarm that quickly activates our immune system at the first sign of an invasion, that the variant carries a mutation that can weaken innate immunity. nose. But more experiments will be required to see if this is truly one of Omicron’s secrets to success.

Dr. “It could be that simple, these people have a lot more virus in their saliva and nasal passages,” Cherry said. But there may be other explanations for its efficient propagation: It may be more stable in the air or better able to infect new hosts. “I think that’s a really important question,” he said.

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