Omicron can cause milder illness. A laboratory study explains why.

The omicron variant of SARS-CoV-2 may be less effective at infiltrating the lungs and spreading from cell to cell, compared to other versions of the coronavirus, suggest the first studies of human cells in a laboratory box.

This may help explain why some early data from countries such as South Africa and England suggests the strain causes less severe disease. But although the omicron cannot invade lung cells efficiently, the new study, published Tuesday, December 21 in the Preprint Database bioRxiv, confirmed that the variant dodges most of the antibody made by fully vaccinated individuals.

And as in other research, the team showed a “booster” dose of Pfizer vaccine dramatically increased the antibody neutralizing power of those vaccinated, “although we still expected a decrease in immunity over time,” lead author Ravindra Gupta, professor of clinical microbiology at the Cambridge Institute for therapeutic immunology and infectious diseases, said in a press release.

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The research has not yet been peer-reviewed or published in a scientific journal, but the results suggest “that omicron mutations exhibit the virus with a double-edged sword: it’s better to escape the immune system, but it might have lost some of its ability to cause serious illness, ”Gupta said. That said, scientists have yet to confirm that these results of experiments in lab dishes match up with what happens in human patients, and that omicron mutations actually influence the severity of infection.

Data from South Africa, England and other countries suggest omicron infections may be less severe, on average, but baseline levels of immunity to natural infections and vaccination make these results difficult to ascertain. to interpret, NPR reported.

Omicron has over 30 mutations in the Genoa which codes for its spike protein, the part of the virus that connects to cells to trigger infection, Previously reported live science. Of these, 10 encode parts of the “receptor binding domain” (RBD), or the specific part of the spike protein that attaches to cells.

To probe how these spike mutations might change the way the virus interacts with cells, the researchers designed synthetic viruses, called pseudoviruses, that carry the spike omicron 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.

The team wanted to understand how three omicron-specific mutations in the polybasic cleavage site (PBCS) affect the ability of the virus to enter cells. Once the spike protein has plugged into a cell, the PBCS cleaves or opens to allow the virus’s genetic material to enter the host cell; alpha and delta variants carry PBCS mutations that help them enter cells more easily, according to a previous study by researchers, published June 8 in the journal Cell reports.

Omicron carries similar mutations in its PBCS genes. So the team predicted that it could slip into cells as easily as alpha and delta. They tested this theory by using their pseudoviruses to infect human lung cells in lab dishes, as well as lung organoids – 3D clumps of cells designed to mimic features of normal-sized lungs. They found that despite its disturbing mutations in PBCS, omicron penetrated lung cells and organoids less efficiently than delta and looked more like Wuhan-1.

Delta also outperformed omicron in a second experiment. On entering a cell, delta pseudoviruses trigger cell fusion, a phenomenon that sticks neighboring cells together and allows the virus to spread rapidly between them. Large-scale cell fusion in the lungs is often seen against the backdrop of severe COVID-19, the researchers noted in their report. However, in their experiments, omicron initiated cell fusion less efficiently than delta, and this appeared to hamper the virus’s ability to replicate in lung cells.

(A separate study, also unpaired, found that omicron replicated much more efficiently than delta in upper respiratory cells, but less efficiently than even the original strain of SARS-CoV-2 in lung cells.)

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“We assume that the more efficient the virus is at infecting our cells, the more severe the disease can be,” Gupta said in the statement. “The fact that omicron is not very efficient at penetrating lung cells and causes fewer fused cells with lower infection levels in the lab suggests that this new variant may cause less severe lung disease.”

Future studies will need to confirm that these experiments in laboratory dishes result in the human body. In the meantime, the team’s experiments with antibodies say that for maximum protection against the variant, people should be given booster shots as soon as possible, Gupta said in the statement.

“People who have only received two doses of the vaccine – or worse, none – are still at significant risk of COVID-19, and some will develop serious illness,” he said. “The large number of new cases that we see every day reinforce the need for everyone to get their recalls as quickly as possible.”

Originally posted on Live Science.