Ômicron is less serious because it spares the lungs, studies show

A series of recent studies done in laboratory animals and human tissue is offering the first indication of why the omicron variant causes milder symptoms than earlier versions of the coronavirus.

In studies carried out with mice and hamsters, the omicron caused infections that were less harmful and, in many cases, were limited to the upper airways: nose, throat and trachea. The variant caused much less damage to the lungs, in which earlier variants often resulted in scarring and severe respiratory distress.

In November, when the first news of the omicron arrived from South Africa, scientists could only offer guesses as to how its behavior might diverge from earlier variants of the virus. All they knew was that omicron had a unique and troubling combination of more than 50 genetic mutations.

Previous research has shown that some of these mutations enable coronaviruses to adhere better to cells. Others allowed the virus to escape antibodies, which act as a first line of defense against infections. But the possible behavior of the new variant within the organism was unknown.

“It is not possible to predict the behavior of a virus from mutations alone,” explained virologist Ravindra Gupta, from the University of Cambridge.

Over the past month, more than a dozen research groups, including Gupta’s, have been looking at the new pathogen in labs, infecting cells in petri dishes with omicrons and spraying the virus on the snouts of animals.

At the same time, the omicron spread across the planet, easily infecting even people who had already been vaccinated or who had recovered from previous infections.

But while Covid’s cases soared, the number of hospitalizations rose only modestly. Initial patient studies suggested that omicron tended to cause less severe disease than other variants, especially in people already vaccinated. Even so, these conclusions were accompanied by many caveats.

To begin with, most early omicron infections have occurred among young people, who are less likely to become seriously ill with any version of the virus. And many of the early cases involved people who already had some immunity from previous infections or from being vaccinated. It was not clear whether omicron would also be less severe with an older, unvaccinated person, for example.

Animal experiments can help dispel these ambiguities because scientists can test the omicron with identical animals living under identical conditions. More than half a dozen experiments reported in recent days have all pointed to the same conclusion: omicron is milder than delta and other earlier versions of the virus.

On Wednesday (29/12) a large consortium of Japanese and American scientists released a report on hamsters and mice infected with omicron or one of several earlier variants. The study showed that those infected with omicrons had less lung damage, had lost less weight and were less likely to die.

Although omicron-infected animals had much milder symptoms, on average, what especially caught the scientists’ attention were the results obtained with Syrian hamsters, a species known to be seriously ill with all previous versions of the coronavirus.

“It was surprising, given that all the other variants seriously infected these hamsters,” said University Washington virologist Michael Diamond and one of the study’s co-authors.

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

The reason the omicron is milder may be a matter of anatomy. Diamond and his colleagues found that the level of omicrons in the noses of hamsters was the same as in animals infected with an earlier form of the coronavirus. But the omicron levels present in the lungs were one-tenth or less than with the other variants.

Researchers at the University of Hong Kong who studied tissue taken from human airways during surgery came to a similar conclusion. In 12 lung tissue samples, the researchers found that the omicron spread more slowly than the delta and other variants.

The scientists also studied infected tissue in the bronchi, the tubes in the upper chest that carry air from the trachea to the lungs. And inside these bronchial cells, in the first two days after infection, the omicron grew faster than the delta or the original coronavirus.

These findings will need to be followed up by further studies, such as experiments with monkeys or an examination of the airways of people infected with the omicron. If the results hold, they may explain why people infected with omicron appear to have a lower risk of hospitalization than those infected with delta.

Coronavirus infections start in the nose or possibly the mouth and spread down the throat. Mild infections don’t go far beyond the throat. But when the coronavirus gets to the lungs, it can cause serious damage.

Lung immune cells can overreact, killing not only infected cells but also uninfected ones. They can produce acute inflammation, marking the delicate walls of the lungs. And the virus can escape from injured lungs into the blood stream, causing clots and damaging other organs.

Gupta thinks his team’s new data offer a molecular explanation of why the omicron does not grow so well in the lungs.

Many cells in the lungs carry a protein called TMPRSS2 on their surface that may inadvertently help pass-through viruses enter the cell. But Gupta’s team found that this protein doesn’t adhere very well to the micron. For this reason, omicron does not infect cells as effectively as delta. A team from the University of Glasgow came to the same conclusion independently.

Through an alternative route, coronaviruses can also penetrate cells that do not produce TMPRSS2. Cells higher up in the airways tend not to have the protein. This may help explain the evidence that omicrons are found in the upper airways more often than in the lungs.

Gupta speculated that the evolution of the omicron made it specialized in the upper airways, propagating well in the throat and nose. If so, the virus may have a better chance of being expelled in droplets into the surrounding air, thus finding new hosts.

“Transmission happens from the upper airways, right?” he said. “It’s not really about what’s going on in the lungs, which is where we see the serious disease. So you can understand why the virus evolved that way.”

These studies clearly help explain why omicron causes milder disease, but they still don’t answer why the variant is transmitted so effectively. More than 580,000 new cases of coronaviruses were reported in the United States on Thursday (12/30) alone, and the majority are believed to have been omicrons.