Omicron may cause milder disease. A lab study hints at why.

The omicron variant of SARS-CoV-2 may be less efficient at infiltrating the lungs and spreading from cell to cell, compared with other versions of the coronavirus, early studies of human cells in a lab dish suggest. 

This may help explain why some early data from countries such as South Africa and England suggest the strain causes less severe disease. But although omicron may not invade lung cells efficiently, the new study, posted Tuesday (Dec. 21) to the preprint database bioRxiv, confirmed that the variant dodges most of the antibodies made by fully vaccinated individuals. 

And similar to other research, the team showed a "booster" dose of the Pfizer vaccine significantly increased the neutralization power of vaccinated people's antibodies, "though we'd still expect a waning in immunity to occur over time," senior author Ravindra Gupta, a professor of clinical microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases, said in a statement.

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The research has not yet been peer-reviewed or published in a scientific journal, but the findings hint "that omicron's mutations present the virus with a double-edged sword: it's got better at evading the immune system, but it might have lost some of its ability to cause severe disease," Gupta said. That said, scientists still need to confirm that these results from experiments in lab dishes match what happens in human patients, and that omicron's mutations actually influence the severity of infection.

Data from South Africa, England and other countries suggest that omicron infections might be less severe, on average, but background levels of immunity from natural infection and vaccination make these results tricky to interpret, NPR reported.

Omicron has more than 30 mutations in the genes that code for its spike protein, the part of the virus that plugs into cells to trigger infection, Live Science previously reported. Of those, 10 code for parts of the "receptor binding domain" (RBD), or the specific portion of the spike protein that latches onto cells. 

To probe how these spike mutations might change how the virus interacts with cells, the researchers engineered synthetic viruses, called pseudoviruses, that carry the omicron spike protein. For comparison, they also generated pseudoviruses with the delta spike protein and some with the Wuhan-1 spike, or that of the original SARS-CoV-2 virus.

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The team wanted to understand how three omicron-specific mutations in the so-called polybasic cleavage site (PBCS) affect the virus's ability to enter cells. After the spike protein plugs into a cell, the PBCS cleaves, or splits open, to allow genetic material from the virus to enter the host cell; the alpha and delta variants carry PBCS mutations that help them enter cells more easily, according to a previous study by the researchers, published June 8 in the journal Cell Reports.

Omicron carries similar mutations in its PBCS genes, so the team predicted that it might slip into cells as easily as alpha and delta do. They tested this theory by using their pseudoviruses to infect human lung cells in lab dishes, as well as lung organoids — 3D clusters of cells made to mimic features of full-size lungs. They found that, despite its concerning PBCS mutations, omicron entered the lung cells and organoids less efficiently than delta and instead more closely resembled Wuhan-1.

Delta also outperformed omicron in a second experiment. Upon entering a cell, the delta pseudoviruses triggered cell fusion, a phenomenon that sticks neighboring cells together and allows the virus to quickly spread between them. Widespread cell-cell fusion in the lungs is often seen in the context of severe COVID-19, the researchers noted in their report. However, in their experiments, omicron initiated cell fusion less efficiently than delta, and this seemed to hinder the virus's ability to replicate in lung cells. 

(A separate study, also not peer reviewed, found that omicron replicated much more efficiently than delta in upper airway cells, but less efficiently than even the original strain of SARS-CoV-2 in lung cells.) 

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"We speculate that the more efficient the virus is at infecting our cells, the more severe the disease might be," Gupta said in the statement. "The fact that omicron is not so good at entering lung cells and that it causes fewer fused cells with lower infection levels in the lab suggests this new variant may cause less severe lung-associated disease."

Future studies will need to confirm that these experiments in lab dishes translate to the human body. In the meantime, the team's experiments with antibodies affirm that to achieve maximum protection against the variant, people should get booster shots ASAP, Gupta said in the statement.

"Individuals who have only received two doses of the vaccine — or worse, none at all — are still at significant risk of COVID-19, and some will develop severe disease," he said. "The sheer number of new cases we are seeing every day reinforces the need for everyone to get their boosters as quickly as possible."

Originally published on Live Science.