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Ravindra Gupta, a virologist at Cambridge University, London, on February 28, 2019 (Jane Stockdale / The New York Times)
A series of new studies in human and laboratory animal tissues is providing us with the first clues as to why the disease caused by the omicron variant is milder than that produced by previous versions of the coronavirus.
In studies with hamsters and mice, omicron was found to cause less damaging infections and that they were almost always largely confined to the upper respiratory tract – nose, throat, and windpipe. This variant caused much less damage to the lungs, which is where previous variants almost always produced fibrosis and great difficulty in breathing.
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 versions of the virus. All they knew was that he had a characteristic and disturbing combination of more than 50 genetic mutations.
Previous research had shown that some of these mutations made the coronavirus more firmly attached to cells. Others enabled him to bypass the antibodies, which form an early line of defense against infection. But it was not known how this new variant could behave within the body.
“It is impossible to 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 teams, including Gupta’s, have been observing the new pathogen in the laboratory, infecting cells with omicron in Petri dishes and spraying the virus into the noses of the children. animals.
While they were working on this, omicron spread all over the planet and began to infect with great ease even vaccinated people or those who had recovered from previous infections.
However, although cases skyrocketed, hospitalizations increased very little. In the first studies carried out in patients it was observed that, unlike what happened with the other variants, people were less likely to get seriously ill with omicron, especially vaccinated people. However, those findings were full of caveats.
First, almost all of the first omicron infections occurred in young people, who are less likely to become seriously ill with either version of the virus. In addition, many of those initial cases were people with some immunity, acquired by previous infections or by vaccines. It was not known, for example, whether omicron would also prove to be less harmful to unvaccinated older people.
Animal experiments can help clarify these questions because scientists can test the omicron variant in identical animals living under identical conditions. More than half a dozen experiments released in recent days came to the same conclusion: omicron is less aggressive than the delta variant and other versions of the virus.
On Wednesday, a large consortium of Japanese and American scientists published a report of work done on hamsters and mice that had been infected with omicron or one of the many previous variants. This study found that omicron-infected animals had less lung damage, lost less weight, and were less likely to die.
Although, on average, the animals infected with omicron presented much milder symptoms, the scientists were very struck by the results obtained in the golden hamsters, a species known to become seriously ill with all previous versions of the virus .
“This surprised us very much, since all the other variants have caused very strong infections in these hamsters,” explained Michael Diamond, a virologist at Washington University and a co-author of the study.
Many other studies in mice and hamsters have reached the same conclusion. (Like the most pressing research on omicron, these studies have been published online, but not yet in scientific journals.)
The reason omicron is less aggressive could be attributed to its anatomy. Diamond and his colleagues found that the amount of omicron introduced into the hamsters’ noses was the same as in animals infected with an earlier version of the coronavirus. But the amount of omicron seen in the lungs was one-tenth less than that of the other variants.
Researchers at the University of Hong Kong who studied fragments of tissue obtained from the airways of humans (by surgery) found something similar. In twelve lung tissue samples, the researchers found that omicron grew more slowly than did delta and other variants.
The researchers also infected tissue in the bronchi, the tubes in the upper chest that carry air from the windpipe to the lungs. During the first two days after infection, omicron grew faster within these bronchial cells than delta or the parent virus did.
These findings need further investigation through other studies, such as experiments in monkeys or through examinations of the airways of people infected with omicron. If the results stand up to scrutiny, they could explain why people infected with omicron appear less likely to have to be hospitalized than those infected with delta.
Coronavirus infections start in the nose or, perhaps, in the mouth and work their way down the throat. Mild infections don’t go much further. But the coronavirus can do a lot of damage when it reaches the lungs.
Immune cells in the lungs can overreact and not only kill infected cells, but also those that are not infected. They can cause fibrosis and acute inflammation in the delicate lung walls. To make matters worse, viruses can escape damaged lungs and enter the bloodstream, form clots, and destroy other organs.
Gupta suspects that his team’s recent data explains, at the molecular level, why omicron doesn’t thrive in the lungs.
Many lung cells carry a protein called TMPRSS2 on their surface, which may inadvertently help passing viruses gain access to the cell. But Gupta’s team found that this protein doesn’t adhere very well to omicron. As a result, omicron does not have the same ability as delta to infect cells in this way. Independently, a team from the University of Glasgow came to the same conclusion.
Via an alternative route, coronaviruses can also sneak into cells that do not make TMPRSS2. In the upper respiratory tract, cells almost never carry proteins, which could explain the finding that omicron is more common in this area than in the lungs.
Gupta supposed that omicron evolved to specialize in the upper respiratory tract and that it multiplies in the throat and nose. If that’s true, the virus is more likely to be released into the surrounding air through tiny droplets that reach new hosts.
“For it to be transmitted, it is important to see what happens in the upper respiratory tract, right?” He said. “It’s not really about what happens in the lungs, where it takes place that makes a person seriously ill. Then we can understand why the virus has evolved like this ”.
Although these studies help to clearly explain why diseases are milder with omicron, they have not yet been able to determine why this variant is transmitted from one person to another so easily. On Thursday alone, the United States had more than 580,000 cases, and it is believed that most of them are omicron.