Nightmare Omicron COVID variants crack the code to our immunity systems

You might not know it from looking around at all those unmasked faces, but there are still so many novel coronavirus the low. And the virus appears to be mutating faster than ever, steadily producing more contagious variants and subvariants.

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

But it underscores an uncomfortable truth: that despite the lifting of COVID restrictions in most countries they are not China, despite many people’s eagerness to overcome the pain and uncertainty of the past two years, the pandemic is not over. The virus has not finished mutating.

The latter subvariants are the most transmissible to date. BA.4 and BA.5, both from the Omicron variant, first appeared in South Africa last month. BA.2.12 and the closely related BA.2.12.1 first performed in New York Around the same time.

BA.4 and BA.5 are 10% more contagious than their immediate predecessor, Omicron’s BA.2 shape. BA.2.12 and BA.2.12.1 are 25% more contagious. Equally alarmingly, BA.4, BA.5, BA.2.12 and B.2.12.1 rapidly become dominant in their respective regions of origin only a few months after BA.2 becomes dominant. BA.2 for its part surpassed and replaced its own parent, BA.1, just months after BA.1 became dominant.

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

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

But this cascade of variants is one of the prices we pay for our population-wide expanding immunity. You can’t have the latter without getting some of the former. So while it might seem like COVID is winning, in fact, its genetic victories might be fleeting.

Niema Moshiri, a geneticist at the University of California, San Diego, last year urged The Daily Beast to view every COVID infection as 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 leveraged strokes twice a month, hoping to hit a genetic jackpot that will give it a new edge over other viruses – and a new way to infect its host.

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

To complete the metaphor, add a growing sense of urgency from the virus as immunity looms higher all around it. Sensing threats all around him, the novel coronavirus is playing slot machines with ever darker determination.

A man adjusts a COVID testing tent in Times Square on April 27.

Spencer Platt/Getty

All along viral waves and crashes of the past 30 months, there have never been less than several million active cases of COVID. During the worst surges in early 2021 and early 2022, there were tens of millions of concurrent infections. Given the high mutation rate of SARS-CoV-2, it is no wonder that the virus has produced a constant lineage of important new variants – “lineage” is the scientific term.

There was Delta, the most virulent bloodline that caused the worst waves of infections of 2021 when much of the world was just beginning to have access to effective therapies and vaccines. At the end of 2022, scientists from 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 grab onto and infect our cells, make Omicron more contagious than Delta. On the worst day of the Omicron wave, January 19, authorities counted no less than 4 million new infections in just 24 hours. That’s four times more cases than they counted on the worst days of back-to-back Delta waves in January and April 2021.

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

Add to that natural antibodies from hundreds of millions of past infections, and the human species’ wall of immunity looks quite impressive. Breakthrough infections are common, but all of these antibodies are really good at stopping the virus from causing serious illness that can lead to death.

Cases therefore increased as Omicron became dominant, but deaths did not. On the deadliest day of the Omicron surge on February 9, 13,000 people died worldwide, 5,000 less than 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 navigate the third year of the pandemic. There are signs that the decoupling may actually be getting more extreme. After all, the immunity that leads to decoupling also causes a virus to mutate more quickly into ever more transmissible lineages.

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

A growing gap between infections and deaths might actually be the best-case scenario, absent the miraculously “self-extinguishing” novel coronavirus rushing into a genetic corner. Many experts strongly believe that an evolutionary dead end is wishful thinking when it comes to respiratory viruses. “I think self-extinction is extremely 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 have to learn to deal with ever more contagious variants and subvariants of SARS-CoV-2 appearing faster and faster. The good news is that we know how to face. BA.4, BA.5, BA.2.12 and BA.2.12.1 have some ability to circumvent our vaccine-induced and natural antibodies – “immune evasion,” experts call it.

A traveler at Los Angeles International Airport wears a face covering April 18 after a federal judge in Florida overturned the nationwide mask mandate covering airplanes and other public transportation.

MediaNews Group/Long Beach Press-Telegram via Getty

Immune evasion does not mean total immune evasion. Natural and vaccine antibodies still work. They are the reason why Omicron baseline cases and deaths have decoupled. This is also why the decoupling is likely with Omicron’s nasty little offspring. “The mutants don’t seem to be as pathogenic as, say, Delta,” Stephanie James, head 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-lines in the coming months as they emerge and become dominant at an accelerating rate. Don’t be surprised if you catch one, even if you’re vaccinated and boosted and maybe even have antibodies from a past infection.

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

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

If ever the virus wins that play, everything changes.

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