Omicron puts scientists on red alert

Omicron, a new variant of the coronavirus, has put the world on red alert. Reports emerged from South Africa on Nov. 24, and 2 days later the World Health Organization dubbed Omicron a variant of concern. The news rattled financial markets and prompted countries to close their borders, though authorities found within a week that the variant was already in Australia, China, Europe, and the US.

The international response to Omicron has been swifter and more severe than for previous variants for two reasons: cases in South Africa are rising more rapidly than expected, and the variant contains an unprecedented number of mutations.

As soon as Omicron’s genetic sequence was shared, scientists began racing to understand whether it will pose a greater challenge to vaccines and therapies than its predecessors.

“It is just a different beast, and that has sent the alarm bells ringing,” says Richard J. Webby, an influenza scientist at St. Jude Graduate School of Biomedical Sciences.

Omicron contains more than 50 mutations, including at least 30 in its spike protein, which the virus uses to infect human cells. The COVID-19 vaccines are based on the original virus’s spike. They spur our immune systems to make antibodies that bind to a crucial region of the spike called the receptor-binding domain. The Delta variant has two mutations in that region, and the Beta variant has three. Omicron has between 10 and 15.

“The list of mutations goes on so much longer in Omicron, and that was really startling to see,” says Rommie E. Amaro, a computational biologist and chemist at the University of California San Diego.

The COVID-19 vaccines were less effective against the Beta variant, which had mutations that helped it partially evade immune responses. But Beta faded as a concern because of the far more transmissible Delta. Omicron shares mutations with Beta and Delta and has many more whose functions are unknown.

“It is pretty clear we are going to take a hit, but we don’t know how big of a hit,” says Nicole Doria-Rose, chief of the Humoral Immunology Core at the US National Institutes of Health’s Vaccine Research Center.

Academic, institutional, and industrial scientists are planning studies to see if antibodies produced from vaccination or natural infection can neutralize Omicron. These tests will take time, as scientists have to either grow the virus or create synthetic versions of it. The first results could come from South Africa in mid-December, and data from other groups should arrive later in the month.

Firms including Johnson & Johnson, Moderna, Novavax, and Pfizer have also announced plans to make new versions of their vaccines tailored to Omicron.

Gilead Sciences, Merck & Co., and Pfizer say their small-molecule antiviral therapies, which target coronavirus enzymes, should work against Omicron, although they plan further testing. Regeneron Pharmaceuticals says the mutations in Omicron’s spike could reduce the ability of its monoclonal antibody therapy, which targets the spike, to neutralize the virus.

“There is a lot that we don’t know” about Omicron, says David Montefiori, an HIV scientist at Duke University Medical Center. Epidemiologists will watch to see if this variant spreads faster than Delta and whether its infections are more or less severe, he says. “I would guess over the next 4 weeks that we will be able to understand that from the way the infections play out in the real world.”