Scientists fear we are not ready for Nightmare New COVID variant

A wave of COVID infections caused by the BA.5 subvariant has peaked. Worldwide, new cases, hospitalizations and deaths are declining daily.

But the SARS-CoV-2 virus is almost certainly here to stay. A second wave is almost inevitable as new variants and subvariants mutate, compete for dominance and find new routes of transmission.

How fast that wave comes, and how bad it gets, will likely come down to a genetic competition between different mutations of the new coronavirus. If we’re lucky, a mild form of the virus wins out – and buys us time to prepare for one worse form of the virus that will almost certainly come, sooner or later.

If we are unfortunatethat worse will come faster.

The scientific community takes nothing for granted. “What we’ve learned from this pandemic is to expect the unexpected,” University of Florida epidemiologist Cindy Prins told The Daily Beast.

BA.5, an offshoot of the basic Omicron variant, was still dominant when epidemiologists began looking for the version of COVID that might come after BA.5. They have identified two main possibilities.

The best of the likely possibilities is yet another form of Omicron, a variant our immune system recognizes and knows how to attack. The worst is a completely new variant that can slip right past our antibodies. A Pi, Rho or Sigma variant, if you will.

Both outcomes are possible. The only thing experts don’t expect is that COVID will just… go away. “The virus always found a way to survive,” John Swartzberg, professor emeritus of infectious diseases and vaccinology at the University of California-Berkeley’s School of Public Health, told The Daily Beast. “I don’t see anything to suggest that it won’t continue to do so.”

BA.5 is the third major subvariant of Omicron, itself the third major variant of the virus after Alpha and Delta. The BA.1, the baseline Omicron, became dominant late last year, replacing forms of the Delta.

BA.1 was not as lethal as Delta was, mainly due to widespread immunity to vaccines and previous infections. The worst day for BA.1 deaths, 13,000 on 9 February, was less catastrophic than the worst day for Delta deaths, 18,000 on 20 January.

But BA.1 was road more contagious than Delta. Some epidemiologists described it as the most transmissible respiratory virus they had ever seen. BA.1 fueled a record wave of infections that peaked with nearly 4.1 million new cases globally on January 19.

But if we get Pi, Rho or Sigma, be prepared for possible disaster.

The BA.1 wave led to two minor increases in cases as new Omicron subvariants took over. BA.1 cases declined in February; BA.2 drove them up again in March. BA.2 infections eased in May. BA.5 drove them up again in June.

The BA.5 surge peaked with 1.6 million new cases on July 20 and 4,500 deaths on July 27. Now, infections and deaths are falling almost everywhere that isn’t Japan.

The relative decline in COVID belies what, by our pre-pandemic standards, is still widespread suffering. “It is quite a reflection of what we have faced in recent years that we may be in a situation with more than 120,000 known new infections per day, more than 43,000 hospitalizations per day – with 5,000 in intensive care units – and 450 deaths per day [in the U.S.] and being in a mindset where we think, ‘This isn’t that bad, we’ve seen worse,'” Anthony Alberg, an epidemiologist at the University of South Carolina, told The Daily Beast.

And the reprieve is temporary. If the past 32 months are any guide, the next wave of COVID will build this winter. The only variable is the form of the virus. Is the next dominant form of SARS-CoV-2 the fourth major Omicron subvariant? Or a completely new variant?

The distinction means a lot. All of the Omicron sublines share certain key mutations, particularly around the virus’ spike protein, the part of the pathogen that helps it grip and infect our cells.

Now billions of people have antibodies that recognize these mutations, whether the antibodies are from one of the safe and highly effective vaccines or from previous infections. It is the steady build-up of immunity over the past two years that has kept the death toll down even though infection rates are rising. Many people have caught COVID since last winter – some for the second or third time. Most had mild cases.

If yet another offspring of Omicron becomes dominant in the next few months, this trend will should Continue. It will probably be a week-long increase in cases. But deaths maybe increase just a little.

Our antibodies are ready, said Edwin Michael, an epidemiologist at the Center for Global Health Infectious Disease Research at the University of South Florida who has built sophisticated computer models to simulate the COVID pandemic.

“Naturally acquired immunity is long-lasting, estimated at 2.5 years in our models, and therefore new infections occur mostly in those who lose their vaccine-induced immunity that decays more quickly,” Michael told The Daily Beast. “This results in a steady but smaller rise and fall of cases, the swings or oscillations becoming progressively smaller in magnitude over time until an apparently endemic steady state is reached.”

But if we get Pi, Rho or Sigma, be prepared for possible disaster.

New variants of a virus become dominant through radical mutations that significantly change how the pathogen behaves – and give it an edge over its predecessors. With each new variant, there is a chance that it has changed so much that our antibodies no longer recognize it. “A major genetic shift that would greatly increase its ability to infect humans regardless of vaccination status and previous infections,” according to Alberg.

Epidemiologists call it “immune escape.” It’s the nightmare scenario when it comes to viruses.

Michael modeled the wave of a large variant of immune escape. How bad it gets depends on whether the new variant avoids vaccine-induced antibodies, natural antibodies from previous infections, or both. “If the immune evasion works the same way on both forms of immunity, you’ll get significant repetitive waves that form depending on the exact speed and strength at which escape occurs,” Michael said.

There are reasons to believe that another Omicron sub-line is likely to come next. Geneticists examining virus samples have noticed four forms of Omicron vying for dominance in recent weeks. BA.5, of course. But also BA.5.2, BA.2.75 and BA.4.6.

BA.5.2 is a slightly mutated form of BA.5 and probably does not have enough advantages to outcompete its predecessor, says Kristian Andersen, director of infectious disease genomics at the Scripps Research Translational Institute in California, to The Daily Beast. “So I think we’ll see BA.2.75 or something completely different become dominant.”

That “something else” hasn’t turned up yet in viral surveillance, meaning BA.2.75 may have a head start.

If it is a wildcard, it could be BA.4.6, a subvariant of BA.4, which is a close cousin of BA.5. “We don’t know much about .4.6 in terms of structure,” Swartzberg said. It is possible that BA.4.6 mutated for significant immune escape despite being only another Omicron subvariant. “We could wish for a new subvariant of Omicron that is so successful in evading immunity [that] it could be a serious problem for us.”

“Be careful what you wish for,” Swartzberg joked.

Still, as long as Omicron and its progeny are dominant, there’s a good chance the next COVID wave will be a pretty small one. That buys us time to prepare for the wave after that—and the increasing likelihood over time that some immune-evasive variant will eventually emerge.

No one expects another round of major shutdowns, even with a highly immune-evasive new form of COVID raging across the planet. Instead, our best tool against Pi, Rho or Sigma may be new formulations of the messenger RNA vaccines from Moderna and Pfizer.

mRNA is inherently flexible. It’s a plug-and-play delivery system for tiny bits of genetic material that trigger a particular immune response. Change the genetic material and you change the vaccine – and the antibodies it induces.

The current mRNA vaccines were designed for the Alpha variant, although they still work very well against Delta and Omicron. In anticipation of the arrival of an immune-escape variant, both Pfizer and Moderna are working on new “multivalent” vaccine formulations with broader efficacy against an even wider range of SARS-CoV-2 variants.

But these new formulations are not entirely clear. Both Massachusetts-based Moderna and New York-based Pfizer have run large-scale trials of their multivalent vaccines, but the US Food and Drug Administration is still scrutinizing the data.

Whether and when the FDA approves new vaccine formulations, a prerequisite for health agencies in many other countries to do the same, may depend on whether and when an immune-escape variant emerges. Swartzberg said the new jabs could receive FDA approval in about a month.

It is clear that regulators would prefer to study the new formulations without the pressure of a large increase in infections and deaths. And they can only get it, if the next wave is a BA.2.75 wave instead of something potentially much worse.

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