Omicron may be milder because it has a less effective way of attacking lung cells, studies say

• Two recent lab studies suggested a reason why Omicron could be more mild than other variants.
• They said its way of attacking cells works badly in the lungs, where the virus does the most damage.
• Conversely, Omicron’s method is more effective elsewhere, which could account for its infectiousness.

The Omicron coronavirus variant may be less severe in humans because it attacks human lung cells in a different way, according to two laboratory studies published recently.

A group of 31 scientists from different universities collaborated on the project for the first study. The second study was authored by 34 scientists from Scottish and English institutes. Both studies were published in preprint form, which means it has yet to be reviewed by other scientists.

The researchers said that Omicron’s numerous mutations appear to have completely changed how it replicated itself in the body.

“[Omicron] is actually doing its own thing in many ways,” Ravindra Gupta, a leading variant researcher from Cambridge University and an author on the first study, told Insider.

“The biology of the virus is not the same as it was before. It’s almost a new thing.”

This provides new evidence supporting the idea that Omicron is less dangerous, Gupta said. Numerous other studies, and some real-world data, have suggested the virus is causing less severe disease and death.

Experts have been hesitant to accept the findings too quickly, hoping for more conclusive data. The paper by Gupta and his colleagues may explain the difference in severity.

Two ways to take over the body

There are two ways the virus can infect a cell. 

One way relies on the shell of the virus fusing with the membrane of the human cell. This route, called “cell surface fusion,” is the route Delta prefers, per Gupta’s previous work.

Cell surface fusion can only be used if a cell carries high levels of a molecule called TMPRSS2, which snips the virus spike protein in half. 

TMPRSS2 is found in large quantities in the lungs, meaning that variants like Delta can thrive there, causing serious damage to the people it infects.

“That is thought to be one of the dominant roots for infection in deep and lung tissue that’s associated with more severe disease,” said Gupta

Delta’s mutations mean it is much better at having its spike protein snipped than other variants, Gupta said.

By contrast, Omicron’s spike protein is very difficult to snip in half, according to lab test results cited in the study on which Gupta is an author. This would make it much worse at infecting the lungs in the way Delta does.

On the other hand, Omicron’s spike protein is much better at binding human cells in general — that gives it an advantage in cells without TMPRSS2, the study said.

Airway cells only have low levels of TMPRSS2, so Omicron is much more suited to infect these cells using a route called “endosomal fusion.” This would make it more capable of causing infections with mild symptoms, but less likely to kill somebody.

These findings come after other lab studies observed Omicron replicating much faster in airway and bronchial cells than in the lungs.

Real-world data supports this finding, as Omicron was found to lead to fewer hospitalizations than Delta in South Africa, in the UK, and in the US.  

These results are preliminary, but support the idea that the variant is inherently less dangerous, rather than the other theory that vaccination and immunity are the cause of less-severe responses.

“So this is what we think ties it all together,” Gupta said. 

Good news and bad news

“We probably need to express some caution. It is nice to see that this variant is potentially less severe. But we don’t know by how much yet,” said Gupta

It’s also not clear whether Omicron could cause other long-term consequences, collectively known as long COVID, as was the case in other variants.

Gupta also warned that it might be possible for future variants to appear that are again more deadly. “The next variant could have combined characteristics, so I don’t think we can be complacent,” he said.