Nightmare Omicron COVID variants are cracking the code on our immunity systems

You may not know it by looking around at all those unmasked faces, but there are still plenty of new coronaviruses out there. And the virus appears to be mutating faster than ever, producing ever more contagious variants and subvariants.

The evolutionary trend of SARS-CoV-2 may not mean that there will definitely be large surges in infections, hospitalizations, and deaths. At least not everywhere or for long.

But it underscores an uncomfortable truth: Despite the lifting of COVID restrictions in most countries other than China, despite the enthusiasm of many people to overcome the pain and uncertainty of the past two years, the pandemic has not is over. The virus has not finished mutating.

The latter subvariants are the most transmissible so far. BA.4 and BA.5, both descendants of the Omicron variant, first appeared in South Africa last month. BA.2.12 and the closely related BA.2.12.1 first appeared in New York at about the same time.

BA.4 and BA.5 are 10 percent more contagious than its immediate predecessor, Omicron’s BA.2 form. BA.2.12 and BA.2.12.1 are 25 percent more contagious. Equally alarming, BA.4, BA.5, BA.2.12 and B.2.12.1 are rapidly becoming dominant in their respective home regions just a couple of months after BA.2 became dominant. BA.2, for its part, outgrew and replaced its own parent, BA.1, just a few months after BA.1 became dominant.

In other words, the major new subvariants seem to be coming to us faster and faster. In that sense, it might seem that the virus is winning a genetic game of chance. Confronted with a semi-permeable barrier of antibodies from past vaccinations and infections, the pathogen becomes more transmissible.

Immune pressure “will increase the selection rate of those fitter variants that are already circulating in the population,” Edwin Michael, an epidemiologist at the University of South Florida Global Health Center for Infectious Disease Research, told The Daily Beast. . “This will result in cascades of new variants appearing and spreading in the host population more frequently.”

But this cascade of variants is a price we pay for our expanding immunity throughout the population. You can’t have the latter without getting some of the former. So while it may appear that COVID is winning, in fact its genetic victories could be fleeting.

Niema Moshiri, a geneticist at the University of California, San Diego, urged The Daily Beast last year to think of every COVID infection like a gambler playing a slot machine. Each individual infection tends to produce two mutations every two weeks, Moshiri explained. In other words, the virus gets two pulls of the lever twice a month, hoping to win a genetic jackpot that will give it some new advantage over other viruses, and some new way to infect its host.

“What if we had 50 million people simultaneously pulling slot machine levers at the same time?” Moshiri asked. “We would expect at least one person to hit the jackpot pretty quickly. Now, replace the slot machine with ‘clinically significant SARS-CoV-2 mutation,’ and that’s the situation we’re in.”

To complete the metaphor, add a growing sense of urgency from the virus as immunity looms higher around it. Sensing threats all around him, the novel coronavirus is playing the slots with an increasingly grim determination.

Throughout the viral waves and crashes of the past 30 months, there have never been fewer than several million active COVID cases. During the worst surges in early 2021 and early 2022, there were tens of millions of simultaneous infections. Given the high rate at which SARS-CoV-2 mutates, it’s no surprise that the virus has produced a steady line of significant new variants — “lineage” being the scientific term.

There was Delta, the most virulent lineage driving the worst waves of infections of 2021 while much of the world was just beginning to gain access to effective therapeutics and vaccines. In late 2022, scientists in Botswana and South Africa detected the first cases of a new lineage, Omicron.

Mutations along the spike protein, the part of the virus that helps it latch onto and infect our cells, make Omicron more contagious than Delta. On the worst day of the Omicron wave on January 19, authorities counted no fewer than 4 million new infections in just 24 hours. That’s four times as many cases as were counted in the worst consecutive delta days in January and April 2021.

Strong global uptake of the vaccine, plus lingering antibodies in tens of millions of people due to past infection, mitigated Omicron’s worst results. When Omicron first appeared, about half of the world’s nearly 8 billion people had received at least one dose of the vaccine. Today, more than two thirds are at least partially punctured.

Add to that the natural antibodies from hundreds of millions of past infections, and the human species’ wall of immunity looks pretty impressive. Progressive infections are common, but all those antibodies are really good at preventing the virus from causing serious illness that can end in death.

So the cases increased as Omicron became dominant, but the deaths did not. On the deadliest day of the Omicron surge on February 9, 13,000 people died globally, 5,000 fewer than died on Delta’s worst day on January 20, 2021.

More cases but fewer deaths, a phenomenon epidemiologists call “decoupling,” has come to define the evolution of COVID as we move into the third year of the pandemic. There are signs that the decoupling could become more extreme. After all, the immunity that leads to uncoupling what’s more it stimulates a virus to mutate more rapidly into increasingly transmissible lineages.

Immunity encourages mutants, which can boost immunity by seeding antibodies from a mild infection. It is an accelerated positive feedback loop whose products are antibodies and viral lineages.

A widening gap between infections and deaths might actually be a best-case scenario, in the absence of the new coronavirus miraculously “self-extinguishing” by finding itself in a genetic corner. Many experts firmly believe that an evolutionary dead end is wishful thinking when it comes to respiratory viruses. “I think self-extinction is becoming more unlikely,” Jesse Bloom, a researcher at the Fred Hutchinson Cancer Research Center in Washington state, told The Daily Beast.

The bad news is that we probably need to learn to deal with increasingly contagious variants and sub-variants of SARS-CoV-2 that are appearing faster and faster. The good news is that we know how coping BA.4, BA.5, BA.2.12, and BA.2.12.1 all have some ability to evade our natural and vaccine-induced antibodies—”immune escape,” the experts call it.

Some immune escape does not mean a total immune escape. Natural and vaccine antibodies continue to work. They are the reason why the cases and deaths from the basic Omicron lineage were decoupled. They’re also the reason he’s likely to decouple with Omicron’s nasty little offspring. “The mutants don’t seem to be as pathogenic as, say, Delta,” Stephanie James, director of a COVID testing lab at Regis University in Colorado, told The Daily Beast.

All that to say, expect to hear a lot about new bloodlines and sub-bloodlines in the coming months as they appear and become dominant at a fast rate. Don’t be surprised if you get one of them, even if you’re vaccinated and boosted and maybe even have antibodies from a previous infection.

But don’t panic. Keep up with your shots and you’ll probably be fine.

Unless, of course, the evolution of SARS-CoV-2 takes a dangerous turn. The immune escape has been pretty minor with all the major lineages and sub-lineages that we’ve seen in the last two years. That doesn’t mean the virus can’t evolve to achieve a significant immune escape. If mutations are like the slot machine pathogen and a jackpot is a new variant, then a variant that can get through our antibodies is a mega jackpot.

If the virus ever wins that bet, everything changes.