Omicron does not infect the lungs very well, animal studies show

A series of new studies in laboratory animals and human tissue provide the first indication of why the Omicron variant causes milder dis...


A series of new studies in laboratory animals and human tissue provide the first indication of why the Omicron variant causes milder disease than previous versions of the coronavirus.

In studies in mice and hamsters, Omicron produced less damaging infections, often limited largely to the upper respiratory tract: the nose, throat, and windpipe. The variant did much less harm to the lungs, where previous variants often caused scarring and severe difficulty breathing.

“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, computer biologist at the Berlin Institute of Health, who has studied how coronaviruses infect the respiratory tract.

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 earlier 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 more tightly to cells. Others have allowed the virus to escape antibodies, which serve as the first line of defense against infection. But how the new variant might behave inside the body was a mystery.

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

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

While they were working, Omicron swept across the planet, easily infecting even people who had been vaccinated or who had recovered from infections.

But as cases have skyrocketed, hospitalizations have increased only modestly. Early patient studies suggested that Omicron was less likely to cause serious illness than other variants, especially in people who were vaccinated. Still, these results came with a lot of caveats.

On the one hand, the bulk of early Omicron infections were among young people, who are less likely to get seriously ill with all versions of the virus. And many of those early cases were in people immune to infections or previous vaccines. It was not clear whether Omicron would also prove to be less serious in an unvaccinated elderly person, for example.

Animal experiments can help dispel these ambiguities, as scientists can test Omicron on identical animals living under identical conditions. More than half a dozen experiments made public in recent days have all come 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 Omicron or one of several earlier variants. According to the study, people infected with Omicron had less lung damage, lost less weight and were less likely to die.

Although animals infected with Omicron had on average much milder symptoms, scientists were particularly struck by the results in Syrian hamsters, a species known to be seriously ill with all previous versions of the virus.

“It was surprising, because all of the other variants heavily infected these hamsters,” said Dr. Michael Diamond, a University of Washington virologist and co-author of the study.

Many other studies on mouse and hamsters came to the same conclusion. (Like most of the urgent research on Omicron, these studies have been posted online but have not yet been published in scientific journals.)

The reason Omicron is softer may be an anatomical issue. Dr Diamond and his colleagues found that the level of Omicron in hamsters’ noses was the same as in animals infected with a previous form of the coronavirus. But the levels of Omicron in the lungs were a tenth or less of the level of the other variants.

A similar conclusion came from researchers at the University of Hong Kong who studied pieces of tissue taken from the 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 tissue in the bronchi, the tubes in the upper part of the chest that carry air from the windpipe to the lungs. And inside those bronchial cells, in the first two days after infection, Omicron grew faster than Delta or the original coronavirus.

These results will need to be followed by other studies, such as experiments in monkeys or examining the airways of people infected with Omicron. If the results stand up to scrutiny, they could explain why people infected with Omicron seem less likely to be hospitalized than those with Delta.

Coronavirus infections start in the nose or perhaps the stuffy and spread into the throat. Mild infections don’t get much further than that. But 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 cells. They can produce uncontrollable inflammation, scarring the delicate walls of the lungs. In addition, viruses can escape from damaged lungs into the bloodstream, causing clots and destroying other organs.

Dr Gupta suspects that the new data from his team gives a molecular explanation for why Omicron does not do as well in the lungs.

Many lung cells carry a protein called TMPRSS2 on their surface which can inadvertently help viruses enter the cell. But Dr. Gupta’s team found that this protein doesn’t attach very well to Omicron. As a result, Omicron succeeds in infecting cells in this way worse than Delta. A team at the University of Glasgow independently came to the same conclusion.

Alternatively, coronaviruses can also slip into cells that do not produce TMPRSS2. Higher in the airways cells tend not to carry the protein, which could explain the evidence that Omicron is found there more often than the lungs.

Dr Gupta speculated that Omicron has become an upper respiratory specialist, thriving in the throat and nose. If this is true, the virus might have a better chance of being expelled in tiny drops into the surrounding air and meeting new hosts.

“It all depends on what’s going on in the upper respiratory tract so that they can transmit, right? ” he said. “It’s not really what’s going on down in the lungs where serious disease occurs. So you can understand why the virus evolved this way. “

While these studies clearly help explain why Omicron causes milder disease, they don’t yet answer why the variant is so effective in spreading from person to person. The United States recorded more than 580,000 cases Thursday only, the majority of which would be Omicron.

“These studies address the question of what can happen to the lungs but do not really address the issue of transmissibility,” said Sara Cherry, virologist at the Perelman School of Medicine at the University of Pennsylvania.

Dr Diamond said he wanted to wait until more studies were done, especially in humans rather than animals, before endorsing the hypothesis that TMPRSS2 is the key to understanding Omicron. “I think it’s still premature about this,” he said.

Scientists know that part of Omicron’s contagiousness comes from its ability to escape antibodies, which allows it to easily enter the cells of vaccinated people much more easily than other variants. But they suspect that Omicron has other biological benefits as well.

Last week, researchers reported that the variant carries a mutation that can weaken so-called innate immunity, a molecular alarm that quickly 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 the secrets of Omicron’s success.

“It could be that simple, it’s a lot more virus in people’s saliva and nasal passages,” Dr. Cherry said. But there could be other explanations for its effective propagation: It could be more stable in air or better infect new hosts. “I think this is really an important question,” she said.

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Newsrust - US Top News: Omicron does not infect the lungs very well, animal studies show
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