Covid Omicron Needs 3 Simultaneous Evolutionary Breakthroughs To Be Dangerous

Vaccine manufacturers will continue to develop new versions to address new variants. The science is no longer that difficult. It is the time required to manufacture and distribute them that creates risk - but the most vulnerable continue to be the willfully unvaccinated. 

For everyone sensible enough to be vaccinated, there remains as yet no evidence that Omicron poses a more serious threat than its predecessor variants. JL

Faye Flam reports in Bloomberg:

Worst case would require the coincidence of three simultaneous evolutionary advances. The variant would have to be transmissible enough to defeat the now-dominant delta strain and thereby spread throughout the human population. It would have to be virulent enough to overwhelm hospitals and provoke damaging lockdowns and restrictions. And it would have to be novel enough to infect and sicken the growing number of people who are immune to previous versions of SARS-CoV-2 by virtue of vaccines or previous illness. That combination of evolutionary surprises is possible, but not all that likely.

There’s a lot to be learned about the omicron coronavirus variant, but scientists already know enough to prescribe a rational response to the threat. As the world waits for data, there’s plenty of useful knowledge that comes from evolutionary biology.

Revamping vaccine formulas and updating travel restrictions to slow down and catch omicron infections make sense, even understanding that the new variant might well fizzle out. Failing to prepare for a worst-case scenario would be a potentially disastrous mistake.

That worst case would require the coincidence of three simultaneous evolutionary advances. The variant would have to be transmissible enough to defeat the now-dominant delta strain and thereby spread throughout the human population. It would have to be virulent enough to overwhelm hospitals and provoke damaging lockdowns and restrictions. And it would have to be novel enough to infect and sicken the growing number of people who are immune to previous versions of SARS-CoV-2 by virtue of vaccines or previous illness.

That combination of evolutionary surprises is possible, but not all that likely. Scientists have been so surprised by the number of mutations in omicron that they’ve been calling it “insane,” but they don’t yet know what they mean.

Some researchers are scrambling to test how well omicron can stand up to the antibodies that are elicited by existing vaccines, and preliminary data show it can bypass these antibodies more readily than existing variants. But antibodies provide only part of the protection immune systems generate, so their potential vulnerability is only part of the story.

On a more optimistic note, the chair of the South African Medical Association, Angelique Coetzee, observed that infections in many of her patients were mild — an indication that omicron is probably not vastly more virulent than existing strains. But since mild cases are common with delta as well, it will take a few weeks to see how they compare.

In the meantime, an understanding of evolution can also inform predictions and decision making — sorting out what’s likely from what’s possible from what’s extremely improbable.

There are two important parts of evolution.

The first is the generation of new diversity through mutations and other genetic changes. In 2020, scientists were thinking that SARS-CoV-2 would do this more slowly than influenza viruses, but because the new virus has spread to so many people in such a short time, it’s getting millions of chances to stumble on new combinations of genes. SARS-CoV-2 can generate new variants by mutations as well as a process called recombination, by which viral particles exchange genetic material.

The other component of evolution is natural selection; survival of the fittest in response to what scientists call evolutionary pressure.

Evolutionary pressure would favor new variants that spread faster than existing versions. That’s why delta took over, and now accounts for more than 99% of cases in the U.S.

There are different ways the virus can become more transmissible. It can get better at multiplying fast in parts of the human respiratory tract where it’s easily aerosolized. It can stumble on better ways to survive in the air, and it can improve its ability to invade the cells of a new host. But delta is already good at all of these — so a successful new variant will have to beat tough competition.

Immunity creates a new evolutionary pressure, bestowing a bigger advantage to newcomers that can evade antibodies from vaccination or past infection. Jesse Bloom, a researcher at the Fred Hutchinson Cancer Research Center, has already jumped into studying omicron, and told me by email that his educated guess is that vaccines will remain at least somewhat effective in preventing severe disease and death.

Then there’s a big wild card: whether the new variant will cause more severe or less severe disease. There’s no evolutionary pressure to make the virus more deadly, so new variants might be more or less deadly by chance. (There’s even a best-case scenario where a new variant comes to dominate and proves relatively harmless, thereby turning the pandemic into something like the flu or the common cold.)

Given what’s known, then, revamping the existing vaccines makes sense, because they’re unlikely to cause different or worse side effects. Moderna has already announced it will start work on making a new booster adjusted for omicron. And BioNTech, Pfizer’s partner, has said it will do the same.

This happened once before. Last week, I learned from Harvard University vaccine researcher Dan Barouch that a previous variant called beta posed enough of a potential threat to prompt pharmaceutical companies to create a new, beta-targeted version of their vaccines. The altered vaccines were never deployed because beta petered out. It couldn’t compete with the ultra-transmissible delta. That could happen again, but hurrying to update the vaccines is a risk worth taking.

Travel restrictions make sense, too, despite objections that they unfairly punish countries such as South Africa for doing good surveillance work and warning the rest of the world.

Since the new variant has already appeared in many other countries, a better approach for the U.S. would be to change travel policy across the board — shifting the focus away from reliance on vaccine passports alone and requiring everyone entering the country to undergo thorough testing for omicron and an appropriate quarantine period. The omicron variant is probably already in the U.S., but it will be easier to understand and combat if it’s not continuously pouring in through unfettered travel.

As for the longer-term outlook, Bloom said that at some point the virus should hit a plateau in its ability to spread between people. Before the pandemic, he studied influenza evolution and indeed, flu viruses keep exchanging pieces of genetic information so they can evade immunity. But they don’t become wildly more transmissible or more deadly year after year. So there’s some hope that science and good policy can keep a step ahead of the virus that causes COVID-19.