Scientists fear we are not ready for nightmare New COVID variant

A wave of COVID infections caused by the BA.5 subvariant has reached its peak. Around the world, daily new cases, hospitalizations and deaths going downstairs.

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

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

if we are bad luckthe worse one comes sooner.

The scientific community doesn’t take anything for granted. “What we’ve learned from this pandemic is to expect the unexpected,” Cindy Prins, a University of Florida epidemiologist, told The Daily Beast.

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

Best of the likely possibilities is yet another form of Omicron, a variant that our immune system recognizes and manages to defeat. The worst is a brand new variant that could slip past our antibodies. A Pi, Rho or Sigma variant, if you will.

Both outcomes are possible. The one thing experts don’t expect is that COVID will just… disappear. “The virus has always found a way to survive,” John Swartzberg, a 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 indicate it won’t continue to do that.”

BA.5 is the third major subvariant of Omicron, itself the third major variant of the virus after Alpha and Delta. BA.1, the baseline Omicron, became dominant late last year, replacing forms of 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 Feb. 9, was less catastrophic than the worst day for Delta deaths, 18,000 on Jan. 20.

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

But if we get Pi, Rho or Sigma, brace yourself for a possible disaster.

The BA.1 wave led to two smaller peaks in cases as new Omicron subvariants took over. BA.1 cases disappeared in February; BA.2 brought them back up in March. BA.2 infections decreased in May. BA.5 brought them back up in June.

BA.5’s rise peaked with 1.6 million new cases on July 20 and 4,500 deaths on July 27. Now the number of infections and deaths is decreasing almost everywhere that is not Japan.

The relative decline in COVID belies what, by our pre-pandemic standards, is still widespread suffering. “It’s quite a reflection of what we’ve been through in recent years that we could 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 ICUs – and 450 deaths per day. [in the U.S.] and being in a mindset where we think, ‘This isn’t so bad, we’ve seen worse,'” Anthony Alberg, a University of South Carolina epidemiologist, told The Daily Beast.

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

The distinction matters a lot. All Omicron sublines share certain key mutations, especially around the virus’s spike protein, the part of the pathogen that helps it grab hold of and infect our cells.

By now, billions of people have antibodies that recognize these mutations, whether the antibodies come from one of the safe and highly effective vaccines or from a previous infection. It is the steady build-up of immunity over the past two years that has kept the death rate low, even as the infection rate rises. Many people have contracted COVID – some for the second or third time since last winter. Most had mild cases.

If another Omicron offspring becomes dominant in the coming months, that trend is should Get on. There will probably a weeks-long rise in cases. But deaths power only slightly increase.

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 advanced computer models to simulate the COVID pandemic.

“Naturally acquired immunity is long-lasting, estimated at 2.5 years in our models, and new infections therefore usually arise 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, with the fluctuations or oscillations getting smaller and smaller over time until an apparently endemic steady state is reached.”

But if we get Pi, Rho or Sigma, brace yourself for a possible disaster.

New variants of a virus become dominant through radical mutations that significantly alter the pathogen’s behavior — giving it an edge over its predecessors. With every 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 significantly increase the ability to infect humans regardless of vaccination status and previous infections,” Alberg said.

Epidemiologists call this ‘immune flight’. It’s the nightmare scenario when it comes to viruses.

Michael modeled the wave of an important immune-escape variant. How bad it gets depends on whether the new variant evades vaccine-induced antibodies, natural antibodies from a previous infection, or both. “If the immune evasion works the same way on both forms of immunity, then you get significantly large repeat waves, depending on the exact speed and strength of escape,” Michael said.

There are reasons to believe that another Omicron subline is likely next. Geneticists examining viral 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 doesn’t have enough benefits to surpass its predecessor, Kristian Andersen, director of infectious disease genomics at the Scripps Research Translational Institute in California, told The Daily Beast. “So I think we’re going to see BA.2.75 or something completely different dominant.”

That “something completely different” hasn’t surfaced in viral surveillance yet, meaning BA.2.75 could have an edge.

If there is a wild card, it could be BA.4.6, a sub-variant of BA.4, a close relative 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 a significant immune system escape, despite being just another Omicron subvariant. “We could wish for a new sub-variant of Omicron that is so successful at evading immunity [that] it could be a serious problem for us.”

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

Still, as long as Omicron and its offspring are dominant, there’s a decent chance the next COVID wave will be a pretty small one. That gives us time to prepare for the wave afterward – and the increasing likelihood, over time, that an immune-evasive variant will eventually show up.

No one expects another round of major lockdowns, not even with a highly immune-evasive new form of COVID raging across the planet. Instead, our best remedy against Pi, Rho or Sigma could be new formulations of the messenger RNA vaccines from Moderna and Pfizer.

MRNA is inherently flexible. It is a plug-and-play delivery system for small pieces of genetic material that trigger a particular immune response. Change the genetic material and you change the vaccine – and the antibodies it induces.

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

But these new formulations are not quite ready yet. Both Massachusetts-based Moderna and New York-based Pfizer have conducted large-scale trials of their multivalent vaccines, but the US Food and Drug Administration is still investigating the data.

Whether and when the FDA approves new vaccine mixes, a prerequisite for health authorities in many other countries to do the same, may depend on whether and when an immune-escape variant appears. Swartzberg said the new shots could be approved by the FDA in about a month.

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

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