Scientists Fear We’re Not Ready for Nightmare New COVID Variant

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A wave of COVID infections caused by the BA.5 subvariant has peaked. Around the world, new cases, hospitalizations and deaths are falling every day.
But the SARS-CoV-2 virus will almost certainly stay. Another wave is all but inevitable as new variants and subvariants mutate, compete for dominance, and find new routes of transmission.
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How fast this wave is coming and how bad it is likely to be related to genetic competition between different mutations of the novel coronavirus. If we're lucky, a mild form of the virus will triumph - buying us time to prepare for a worse form of the virus that will almost certainly come sooner or later.
When we're unlucky, the worse comes sooner.
The scientific community takes nothing for granted. "What we've learned from this pandemic is to expect the unexpected," Cindy Prins, an epidemiologist at the University of Florida, 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. You have identified two main possibilities.
One thing stands between us and the COVID vaccine of our dreams
The best of the most likely possibilities is another form of Omicron, a variant that our immune system recognizes and knows how to defeat. The worst is a brand new variant that could slip right past our antibodies. A pi, rho or sigma variant, if you will.
Both outcomes are possible. The only thing experts don't anticipate is that COVID will just... go away. "The virus has 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 it won't continue to do so."
BA.5 is the third major variant of Omicron, itself the third major variant of the virus after Alpha and Delta. BA.1, the Omicron baseline, became dominant late last year, replacing forms of Delta.
BA.1 was not as deadly as Delta, largely due to widespread immunity to vaccines and past infections. The worst day for BA.1 deaths, 13,000 on February 9, was less catastrophic than the worst day for Delta deaths, 18,000 on January 20.
But BA.1 was much more contagious than Delta. Some epidemiologists have described it as the most transmissible respiratory virus they have ever seen. BA.1 led to a record wave of infections, peaking on January 19 with nearly 4.1 million new cases worldwide.
The BA.1 wave resulted in two smaller increases in some cases as new Omicron subvariants took over. BA.1 cases resolved in February; BA.2 drove them up again in March. BA.2 infections declined in May. BA.5 brought them back up 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 except Japan.
The relative decline of COVID belies what is still a widespread ailment by our pre-pandemic standards. "It pretty much reflects what we've seen over the last few years that we could be in a situation where we could be in a situation where there are more than 120,000 known new infections per day, more than 43,000 hospital admissions per day - of which 5,000 are in intensive care units - and 450 deaths per day [ in the US] and in a mindset where we're like, 'This isn't so bad, we've seen worse,'" Anthony Alberg, an epidemiologist at the University of South Carolina, told The Daily Beast.
And the grace period is temporary. If the last 32 months are any indication, the next wave of COVID will build up 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 whole new variant?
The distinction is very important. All Omicron sublineages share certain key mutations, particularly around the virus's spike protein, the part of the pathogen that helps it take hold and infect our cells.
Billions of people now 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's the steady build-up of immunity over the past two years that has kept death rates low even as infection rates are rising. Many people have contracted COVID since last winter - some for the second or third time. Most had mild cases.
If another Omicron offspring becomes dominant in the next few months, this trend should continue. There will likely be a week-long spike in cases. But deaths could increase only slightly.
Our antibodies are ready, said Edwin Michael, an epidemiologist at the University of South Florida's Center for Global Health Infectious Disease Research, 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 new infections therefore arise mostly in those who lose their vaccine-induced immunity, which wears off more quickly," Michael told The Daily Beast. "This results in a steady but smaller rise and fall in cases, with the swings or oscillations becoming smaller and smaller over time until a seemingly endemic steady state is reached."
But if we do get pi, rho, or sigma, brace yourself for potential catastrophe.
New variants of a virus become dominant through radical mutations that significantly change the behavior of the pathogen - and give it an edge over its predecessors. With every new variant, there is a chance that it will change so much that our antibodies will no longer recognize it. "A major genetic change that would significantly increase its 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 rise of a large immune escape variant. How bad it gets depends on whether the new variant bypasses vaccine-induced antibodies, natural antibodies from a past infection, or both. "If immune avoidance acts similarly on both forms of immunity, then significantly large repeat waves will form, depending on the exact rate and strength at which escape occurs," Michael said.
There is reason to believe that another Omicron subline will likely be next. Genetics studying viral samples have identified four forms of omicron that have been 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 advantages to outperform 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 else entirely become dominant."
This “something very different” has yet to show up in virus surveillance, which means BA.2.75 could have a head start.
If there is a wildcard, it could be BA.4.6, a subvariant of BA.4 that 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 is mutated for significant immune escape, although it is just another subvariant of Omicron. "We could wish for a new subvariant of Omicron that is so successful at bypassing immunity [that] it could pose a serious problem for us."
"Be careful what you wish for," Swartzberg quipped.
Still, as long as Omicron and his progeny are dominant, there's a good chance the next COVID wave will be fairly small. This buys us time to prepare for the wave after - and the increasing likelihood over time that an immune-avoidable variant will eventually emerge.
Nobody expects another round of major lockdowns, even as a highly immune-preventable new form of COVID rages across the planet. Instead, new formulations of Moderna and Pfizer's messenger RNA vaccines could be our best tool against Pi, Rho, or Sigma.
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MRNA is inherently flexible. It's a plug-and-play delivery system for tiny scraps of genetic material that trigger a specific immune response. Change the genetic material, 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 an Immunescape variant, both Pfizer and Moderna are working on new "multivalent" vaccine formulations with broader potency against an even broader spectrum 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 reviewing the data.
If and when the FDA will approve new vaccine blends, a requirement for health officials in many other countries to do the same, could depend on if and when an immune-escape variant emerges. Swartzberg said the new injections could be approved by the FDA in about a month.
Obviously, regulators would prefer to study the new formulations without the pressure of a large spike in infections and deaths. And they might get that if the next wave is a BA.2.75 wave and not something potentially much worse.
Read more at The Daily Beast.
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