Explanation: Studies suggest why Omicron is less severe: it saves the lungs

Explanation: Studies suggest why Omicron is less severe: it saves the lungs


A number of new studies in laboratory animals and human tissues provide the first indication of why the omicron variant causes a milder disease than previous versions of coronavirus.

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

“It’s fair to say that the idea of ​​a disease that mainly manifests in the upper respiratory system is emerging,” said Roland Eils, a computer biologist at the Berlin Institute of Health, who has studied how coronaviruses infect the airways.

In November, when the first report on the omicron variant came out of South Africa, scientists could only guess how it might behave differently from previous forms of the virus. All they knew was that he had a distinctive and alarming combination of over 50 genetic mutations.

Previous research had shown that some of these mutations allowed coronaviruses to attach to cells more strongly. Others allowed the virus to escape antibodies, which serve as the first line of defense against infection. But how the new variant within the body might behave was a mystery.

“Virus behavior cannot be predicted from mutations alone,” said Ravindra Gupta, a virus expert at Cambridge University.

Over the past month, more than a dozen research groups, including Gupta’s, have been observing the new pathogen in the lab, infecting petri dish cells with omicron and spraying the virus on the animals’ noses.

As they worked, omicrons grew all over the planet, easily infecting even people who were vaccinated or had recovered from infections.

But as cases skyrocketed, hospitalizations increased only modestly. Early patient studies suggested that omicron was less likely to cause serious illness than other variants, especially in vaccinated individuals. However, these findings came with many warnings.

On the one hand, most early omicron infections occurred in young people, who are less likely to become seriously ill with all versions of the virus. And many of these early cases were happening in people with some immunity to previous infections or vaccines. It was unclear whether omicron would also be less severe in an unvaccinated elderly person, for example.

Animal experiments can help clarify these ambiguities, because scientists can test omicrons in identical animals that live in identical conditions. More than half a dozen experiments made public in recent days have led to the same conclusion: Omicron is lighter 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 omicron or one of several previous variants. Omicron-infected people had less lung damage, lost less weight, and were less likely to die, according to the study.

Although omicron-infected animals on average experienced much milder symptoms, scientists were especially shocked by the results in Syrian hamsters, a species known to be seriously ill with all previous versions of the virus.

“This was surprising, as all other variants have robustly infected these hamsters,” said Dr. Michael Diamond, a virus expert at the University of Washington and co-author of the study.

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

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The reason why omicron is lighter may be a matter of anatomy. Diamond and colleagues found that the level of omicron in the noses of hamsters was the same as in animals infected with a previous form of coronavirus. But omicron levels in the lungs were about a tenth of the level of other variants.

A similar finding came from researchers at the University of Hong Kong who studied fragments of tissue extracted from human airways during surgery. In 12 lung samples, the researchers found that omicron grew more slowly than delta and other variants.

Researchers also infected bronchial tissues, the tubes in the upper chest that carry air from the trachea to the lungs. And within these bronchial cells, in the first two days after an infection, the omicron grew faster than the original delta or coronavirus.

These findings should be followed by 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 could explain why people infected with omicron appear less likely to be hospitalized than those with delta.

Coronavirus infections begin in the nose or possibly in the mouth and spread down the throat. Mild infections do not go far beyond that. But when the coronavirus reaches the lungs, it can cause serious damage.

Lung immune cells can overreact, killing not only infected but also uninfected cells. They can cause uncontrolled inflammation, which scars the delicate walls of the lung. In addition, viruses can escape from damaged lungs into the bloodstream, causing clots and destroying other organs.

Gupta suspects new data from his computer gives a molecular explanation for why omicron is not doing so well in the lungs.

Many cells in the lung carry a protein called TMPRSS2 on their surface that can inadvertently help passing viruses into the cell. But Gupta’s team found that this protein doesn’t stick very well to the omicron. As a result, omicron does a worse job of infecting cells in this way than delta. A team from the University of Glasgow came to the same conclusion independently.

Through an alternative pathway, coronaviruses can also enter cells that do not produce TMPRSS2. Above the airways, cells tend not to carry protein, which could explain the evidence that omicron is found more often than lungs.

Gupta speculated that omicron became a specialist in the upper respiratory tract, thriving in the throat and nose. If this is true, the virus may be more likely to be expelled in small droplets into the surrounding air and find new guests.

“It’s all about what’s going on in the upper airways for it to be transmitted, right?” He said. “It’s not really going down to the lungs, where the serious things of the disease happen. So you can understand why the virus has evolved this way.”

While these studies clearly help explain why omicron causes a milder disease, they still don’t answer why the variant is so good at spreading from person to person. The United States reported more than 580,000 cases on Thursday alone, most of which are believed to be omicron.

“These studies address the question of what can happen to the lungs, but they don’t really address the issue 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, especially in humans instead of animals, before supporting the hypothesis that TMPRSS2 is the key to understanding omicron. “I think it’s still premature on that,” he said.

Scientists know that some of the contagiousness of omicron comes from its ability to evade antibodies, which allows it to easily enter the cells of vaccinated people much more easily than other variants. But they suspect that omicron also has other biological benefits.

Last week, researchers reported that the variant carries a mutation that can weaken the so-called innate immunity, a molecular alarm that quickly activates our immune system at the first sign of a nose invasion. But more experiments will be needed to see if this is really one of the secrets of omicron’s success.

“It could be as simple as, that’s 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 guests. “I think that’s a really important question,” he said.



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