A wave of COVID infections caused by the BA.5 subvariant has peaked. Around the world, new daily cases, hospitalizations and deaths are on the decline.
But the SARS-CoV-2 virus is almost certainly here to stay. Another wave is almost inevitable as new variants and sub-variants mutate, compete for dominance and find new routes of transmission.
How quickly this wave comes and how severe it becomes likely comes down to genetic competition between different mutations in the novel coronavirus. If we’re lucky, a mild form of the virus wins out and buys us time to prepare for a worse form of the virus that will almost certainly arrive, sooner or later.
Whether unluckythat worst comes sooner.
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 base Omicron variant, was still dominant when epidemiologists began searching for which version of COVID might come after BA.5. They identified two main possibilities.
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The best of the probable possibilities is yet another form of Omicron, a variant that our immune system recognizes and knows how to beat. The worst is a whole new variant that could evade our antibodies. A Pi, Rho or Sigma variant, if you will.
Either outcome is possible. The one thing experts don’t expect is for COVID… to 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, School of Public Health told The Daily Beast. “I don’t see anything to suggest he’s not going to keep doing that.”
BA.5 is the third major sub-variant of Omicron, itself the third major variant of the virus after Alpha and Delta. BA.1, Omicron’s baseline, became mainstream late last year, replacing the Delta shapes.
BA.1 was not as lethal as Delta, mainly 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 way 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 that peaked at nearly 4.1 million new cases worldwide on January 19.
The BA.1 wave brought two smaller increases in the number of cases as new Omicron subvariants took over. BA.1 cases subsided in February; BA.2 pushed them back in March. BA.2 infections decreased in May. BA.5 brought them back up in June.
The BA.5 outbreak peaked with 1.6 million new cases on July 20 and 4,500 deaths on July 27. Now infections and deaths are declining almost everywhere outside of Japan.
The relative decline of COVID belies what, by our pre-pandemic standards, is still widespread suffering. “It is very reflective of what we have faced over the past few years that we could be in a situation with more than 120,000 new known infections per day, more than 43,000 hospitalizations per day – including 5,000 in ICU – and 450 deaths per day. [in the U.S.] and being in a state of mind where we think, ‘It’s not 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 COVID wave 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 subvariant of Omicron? Or a totally new variant?
The distinction matters a lot. All Omicron sublines share some key mutations, particularly around the virus’ spike protein, the part of the pathogen that helps it latch onto and infect our cells.
Right 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 past infection. It is the steady buildup of immunity over the past two years that has kept death rates low even as infection rates rise. 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 coming months, this trend should Carry on. There will be Most likely be a multi-week increase in cases. But the dead strength increase only slightly.
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 new infections therefore occur mainly in those who lose their vaccine-induced immunity which breaks down more quickly,” Michael told the Daily. beast. “This results in a steady but smaller rise and fall in cases, with the fluctuations or oscillations becoming progressively smaller over time until an apparent endemic steady state is reached. “
But if we get Pi, Rho or Sigma, prepare for possible disaster.
New variants of a virus become dominant through radical mutations that dramatically alter the behavior of the pathogen 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 change that would greatly increase its ability to infect humans, regardless of vaccination status and prior infections,” according to Alberg.
Epidemiologists call this “immune evasion”. This is the virus nightmare scenario.
Michael modeled the outbreak of a major variant of immune evasion. The severity of the situation depends on whether the new variant avoids vaccine-induced antibodies, natural antibodies from a previous infection, or both. “If immune evasion acts the same way on both forms of immunity, you’ll get significantly large repeated waves depending on the exact speed and strength with which the evasion occurs,” Michael said.
There is reason to believe that another Omicron sub-lineage is most likely to come next. Geneticists examining viral samples have noted 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 mildly mutated form of BA.5 and probably doesn’t have enough of an edge 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’ll see BA.2.75 or something completely different become dominant.”
This “something completely different” has yet to show up in virus surveillance, meaning BA.2.75 may have a head start.
If there 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 evasion although it is just another sub-variant of Omicron. “We could wish for a new sub-variant of Omicron that is so successful in evading immunity [that] this could be a serious problem for us.
“Be careful what you wish for,” Swartzberg joked.
Still, as long as Omicron and his offspring are dominant, there’s a good chance the next wave of COVID will be quite small. It buys us time to prepare for the wave that will follow – and the increasing likelihood, over time, that an immune evasive variant will eventually emerge.
No one expects another round of major lockdowns, even with a new, highly immune form of COVID raging across the planet. Instead, our best tool against Pi, Rho or Sigma might be new formulations of the messenger RNA vaccines from Moderna and Pfizer.
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RNAM is inherently flexible. It is 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.
Current mRNA vaccines were designed for the Alpha variant, although they still work very well against Delta and Omicron. Anticipating the arrival of an immune evasion variant, 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 quite ready. 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 approves new vaccine mixtures, a prerequisite for health agencies in many other countries to do the same, it could depend on whether and when an immune evasion variant appears. Swartzberg said the new jabs could get FDA approval in about a month.
Clearly, regulators would prefer to study new formulations without the pressure of a sharp rise in infections and deaths. And they just might get it, if the next wave is a BA.2.75 wave instead of something potentially much worse.
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