Experts Predict What The Next COVID-19 Variants Will Be Like


HuffPost 04 August, 2021 - 04:45am 53 views

What shocked scientists is the rate of evolution, or how quickly these variants of concern acquired new mutations, according to Nathan Grubaugh, an evolutionary virologist and associate professor of epidemiology at the Yale School of Public Health. In general, the coronavirus acquires about one or two mutations a month. But the variants of concern have acquired many more mutations much more quickly. Alpha, for example, didn’t just acquire one or two mutations, it picked up 17.  

According to Grubaugh, the same sort of rapid increase in mutations was identified with the beta variant detected in South Africa and the gamma variant that popped up in Brazil. “This phenomenon that we’re watching, of these variants that arise very quickly, I think caught a lot of us off guard,” Grubaugh said. 

It’s impossible to predict exactly what future variants will look like, but it’s pretty undeniable that we are going to see new variants emerge.

“We haven’t seen the end of variants and we certainly haven’t seen the end of variants that are more transmissible,” Grubaugh said. 

The development of new variants that rise to the level of concern is actually extremely rare. There have probably been hundreds of thousands of events where a host of new mutations have occurred, but those versions of the virus weren’t very fit so they died out before becoming a variant of concern. Just because the virus evolves, doesn’t mean it’s going to become a variant of concern.

But, when you give the virus so many different opportunities to infect new people, it will inevitably test out new variations. As long as there are people for SARS-CoV-2 to infect, the coronavirus will continue to evolve.

“We know that most of the variants we see emerge from people who are not vaccinated,” said Dirk Dittmer, a virologist at the University of North Carolina’s School of Medicine who is currently working on a variant tracking project in North Carolina

We’ve never seen anything like SARS-CoV-2 before. We’ve never had a pandemic of this scale with so much global mixing. A variant that pops up in Brazil can be in Japan or the United States in a moment’s notice, Grubaugh said. What happens around the globe is going to impact the rest of the world — we aren’t living in a vacuum. This makes it a lot harder to predict what’s going to emerge and where. 

“The key to stopping new variants is to vaccinate so thoroughly that SARS-CoV-2 is not able to find enough new hosts to sustain itself.”

Read full article at HuffPost

GoLocalProv | News | What Comes After Delta? RI’s Exploding Cases Creates Vulnerabilities for Dangerous New Variants

GoLocalProv 04 August, 2021 - 12:20pm

Now, Rhode Island's spread of the virus is one of the highest in the country.

Recent clinical studies have shown that the current mRNA vaccines are only about 40% effective in preventing infection or symptomatic illness, compared with 95% against the original strain, and even more recent studies confirm that vaccine effectiveness declines over time.

How long it will take before a completely resistant variant emerges is impossible to predict, but there are already two on the horizon that have been identified with potentially even greater resistance to the vaccines: Lambda (C.37), and B.1.621.

The code for how the virus is built is its ‘nucleotide sequence’, a set of about 30,000 ‘letters’ of RNA, ribonucleic acid.  As an infected cell builds new coronaviruses, it occasionally makes tiny copying errors as it reproduces, called mutations, which are a change in any one of these ‘letters’. These mutations can be tracked as they are passed down through a lineage, which is a branch of the viral family tree. A group of coronaviruses that share the same inherited set of mutations is called a variant. If enough mutations accumulate in a lineage, the viruses may evolve clear-cut differences in how they work. These lineages are known as strains. The disease COVID-19 is caused by a coronavirus strain known as SARS-CoV-2.

Mutations are random and most are irrelevant or can even be damaging to the virus. However, the rules of evolution select for mutations that help the virus survive. With billions and billions of mutations happening all the time, some turn out to be beneficial to the virus – which are usually harmful to us. Once that happens, a new variant can spread fast and quickly become dominant in an area. This has now happened several times around the world including Rhode Island. Earlier this year the Alpha variant (also called B.1.1.7) become dominant and has now been replaced by the more aggressive Delta (B.1.617.2). More are coming.

There are several ways for the coronavirus to mutate to increase its chances for survival, including:

The Delta variant has developed several of these weapons with its mutations. It creates over 1,000 times more copies of itself in our bodies more quickly, and thus spreads more easily and causes more serious illness. It is also partially resistant to vaccines because of changes to the shape of its spike protein that make it harder for antibodies created by vaccines to bind to it.

Because Delta reproduces so much faster with so many more copies of itself than previous strains, it can also create even more mutations and variants faster than ever before. The more copies of a virus there are, the more mutations and variants will be created.

The variants are getting better at evading our weapons, which is the natural process of evolution. Alpha was more contagious than the original strain, and Delta is more contagious than Alpha.

We also have to worry not just about new variants, but the declining effectiveness of vaccines over time. Antibody levels in our bodies decrease over time, making us more susceptible to aggressive variants.

The Pfizer and Moderna vaccines are initially about 95% effective. This drops to 70% by 200 days after vaccination, and 50% by 250 days. The antibodies from the Astra-Zeneca vaccine reach near zero after just 70 days.

As a result, Israel, Germany, and the United Kingdom have all decided to give third, booster shots of vaccine starting with older people.

Delta Variant may have killed a million in India PHOTO: Ninian Reed CC 2.0

Thousands of variants have been identified since the start of the pandemic. The total number of possible mutations is ridiculously high, and the number of potential variants impossible to predict.

Two new worrisome variants are already on the horizon. Little is known about them so far since they are so new, but enough to be concerned that they may continue the evolutionary drive of Alpha and Delta and be even more resistant to our vaccines.

Lamba (also called C.37) was first identified in Peru. It contains 7 mutations in the virus’s ‘spike’ region, including one, termed F490S, that a recent study says maybe a ‘vaccine escape mutation’. Studies have shown that it is more resistant to antibodies from vaccines than previous variants.

The B.1.621 variant is so new that it has not yet been assigned a Greek ‘letter’ name. It was first identified in Columbia, and has already spread so fast that it accounts for 10% of cases in Florida.

The European Center for Disease Control and Prevention has also named B.1.621 as a variant of interest, as the preliminary scientific evidence suggests it could have significant impact.

B.1.621 has several mutations in the ‘spike’ region. It’s rapid appearance and rise in such a short time in places that had good vaccination rates suggests it could be a major problem in the future.

As serious as the Delta variant is and as calamitous as the problems it is causing for us today, and as worrisome as the Lambda and B.1.621 variants appear to be, the pandemic will not end with them. Science has a great deal more to learn about the SARS-CoV-2 virus, but it is certain that evolution of the virus will continue, and rapidly, in ways to make it spread more quickly.

It is sometimes presumed that viruses generally evolve towards becoming less lethal, and some hope the SARS-CoV-2 virus might someday become more like the common cold. This is a dangerous assumption.

There are no evolutionary pressures to drive the SARS-CoV-2 virus to become more benign to humans. Evolution would indeed select against a virus that killed swiftly. For example, while Ebola is highly contagious, it has not become a widespread pandemic because it kills its victims quickly, before they have a chance to infect many others.

The SARS-CoV-2 virus does not behave this way. Death comes late in the COVID-19 infection process, leaving the virus plenty of time to reproduce and infect many new victims. Killing someone late in the infection process doesn’t inhibit a variant from propagating. A hypothetical coronavirus variant so virulent that it killed its targets early on would likely not become dominant and probably be an evolutionary dead end, but more virulent late killers like Delta do just fine. While there are no evolutionary advantages to drive the virus to kill faster, it would be naïve to hope that the coronavirus will rapidly evolve in ways to suit our purposes just to make us happy.

Rhode Island has done well with vaccinations, currently fifth in the country for fully vaccinated However, the Delta experience is painfully showing us that vaccination alone is not enough. The pandemic will not be contained solely by vaccination. It is a critically important tool for reducing severe illnesses and deaths, but other efforts are needed in addition to vaccination. “Herd immunity” simply is not possible with current vaccines. If we want to avoid a repeating pattern of surges, infections, overcrowded hospitals, and soaring deaths going on for many years into the future, then we need to shift strategy and do more.

Other states and countries grasp the enormity of the danger before us, and are responding in prudent, science-driven ways. France now requires proof of vaccination to enter restaurants, bars, and other public places, and New York City is adopting a similar approach and also requiring vaccination to enter restaurants and gyms. Many areas are following the recommendations of both the Centers for Disease Control and the World Health Organization by asking for masks in indoor spaces.

Governor McKee seems to be following Governor Raimondo’s example and other than vaccination, is currently doing almost nothing to respond to the greatest public health crisis in over a century. This is creating ideal conditions for new variants to form and spread in Rhode Island. Lambda and B.1.621 are hints at what is coming next after Delta. It will get worse before it gets better, and we are not prepared.

Other than vaccinations, Rhode Island has done a poor job at safeguarding our health and lives. We still have the second-highest overall infection rate in the country, and the fourth-highest per capita death rate. We are the only state in the top 5 for both.

The risk level in Rhode Island is “Very High”, and our COVID cases are up about 1,500% in the past month Rhode Island is experiencing the second fastest growth rate of new COVID cases in the country.

At this rate, we should not be surprised to see a new “Rhode Island Variant” in our future.

A doomsday COVID variant worse than Delta and Lambda may be coming, scientists say

The Weather Channel 04 August, 2021 - 04:00am

Scientists keep underestimating the coronavirus. In the beginning of the pandemic, they said mutated versions of the virus wouldn't be much of a problem—until the more-infectious Alpha caused a spike in cases last fall. Then Beta made young people sicker and Gamma reinfected those who'd already recovered from COVID-19. Still, by March, as the winter surge in the U.S. receded, some epidemiologists were cautiously optimistic that the rapid vaccine rollout would soon tame the variants and cause the pandemic to wind down.

Delta has now shattered that optimism. This variant, first identified in India in December, spreads faster than any previous strain of SARS-CoV-2, as the COVID-19 virus is officially named. It is driving up infection rates in every state of the U.S., prompting the Centers for Disease Control and Prevention (CDC) to once again recommend universal mask-wearing.

The Delta outbreak is going to get much worse, warns Michael Osterholm, an epidemiologist who leads the Center for Infectious Disease Research and Policy at the University of Minnesota. "The number of intensive-care beds needed could be higher than any time we've seen," he says. He adds that his team's analysis shows that almost every single one of the 100 million unvaccinated Americans who hasn't had COVID-19 yet will likely get it in the coming months, short of taking the sort of strong isolation and masking precautions that seem unlikely in the vaccine-hesitant population.

The variant is so contagious that it's set to smash through every previous prediction of how soon the U.S. might reach herd immunity. "We've failed to shut this down as we have other pandemics," says Jonathan Eisen, a biologist at the University of California, Davis, who studies how pathogens evolve. "It may be around forevermore, leaving us continually trying to figure out what to do next."

Delta, like most of the other variants, blindsided us, worsening and extending the pandemic. When the damage from Delta starts to subside, what other variants will be lurking just behind it to pull us back down again? The World Health Organization is already keeping an eye on several: Eta, which is now in several countries; Kappa, which arose in India; Iota, which first popped up in New York City—and especially Lambda, which has torn through Peru and shows signs of having unusual success in infecting fully vaccinated people, according to one early study. It has already spread to Argentina, Chile, Ecuador as well as Texas and South Carolina.

It's too soon to say whether Lambda will turn out to be the next big, bad thing that COVID-19 unleashes on us. But it's a good time to wonder: Just how destructive can these variants get? Will future variants expand their attack from the lungs to the brain, the heart and other organs? Will they take a page from HIV and trick people into thinking they've recovered, only to make them sick later? Is there a Doomsday variant out there that shrugs off vaccines, spreads like wildfire and leaves more of its victims much sicker than anything we've yet seen?

The odds are not high that we will see such a triple threat, but experts can't rule it out. Delta has already shown how much worse things can get. Its extreme contagiousness, with room to run freely through the tens of millions of Americans who haven't been vaccinated and millions more who have no access to vaccines in developing countries, has good odds of turning into something even more troublesome. "The next variant," says Osterholm, "could be Delta on steroids."

It wasn't supposed to happen this way. Early in the pandemic, most experts closely studying COVID-19 mutations downplayed the notion that variants would cause such serious problems. "They don't seem to make much of a difference," said Richard Neher, an evolutionary biologist at Switzerland's University of Basel, in August last year. "We probably only need to worry about it on a timescale of about five years." Today he calls Delta and other COVID-19 variants "the pandemic within the pandemic."

Delta, more than any other variant, has reset scientists' understanding of how quickly a virus can evolve into devastating new forms. "All coronaviruses mutate, and we knew this one was mutating, too," says Sharone Green, a physician and infectious disease researcher at the University of Massachusetts Medical School. "But we didn't think the mutations would so strikingly affect transmissibility and possible evasion of immunity."

It may seem surprising that scientists were caught off-guard by the rapid emergence of a more dangerous variant. But unlike most other pathogens, Eisen notes SARS-CoV-2 was largely unknown when it emerged. In the absence of data, scientists assumed it would follow other viruses in being relatively slow to spin off much more contagious mutations. Even more important, he adds, scientists underestimated the sheer scale the pandemic would eventually achieve—a critical factor, because the more people a virus infects, the more opportunities it has to develop significant mutations. "Having billions of people infected presents a breeding ground for variants unlike anything we've ever seen with these sorts of viruses," he says.

SARS-CoV-2 doesn't mutate particularly quickly, compared to many pathogens. Just as with most human and other cells, a mutation occurs in a virus when it replicates but fails to make a perfect copy of its genetic material. That imperfect copy is a mutant. The COVID-19 virus doesn't have a lot of genetic material to scramble compared to most organisms—about 15 genes, versus about 3,000 genes in an E. coli bacterium, a run-of-the-mill stomach bug, and about 20,000 in a human cell. What's more, COVID-19 has genetic checking mechanisms that make it reasonably adept at avoiding replication mistakes compared to most viruses.

But while COVID-19's mutation rate is on the low side—about one mutation for every 10 replications, or around a fifth of the flu's mutation rate and a tenth of HIV's—COVID-19 takes advantage of a grim numbers game. A single person infected with COVID-19 might carry 10 billion copies of the virus, enough to produce billions of mutated viruses every day. What happens to all those mutations? Almost always the answer is: nothing. The genetic scrambling is random, with the result that virtually all mutations either have no effect whatsoever on the virus, or else do something that makes the virus less effective or even renders it entirely non-functional.

But once in a while—perhaps every million trillion times—a random mutation confers some potentially dangerous new characteristic. What's more, much of what makes the virus dangerous has to do with a relatively small portion—the so-called spike proteins that protrude from its surface and enable the virus to latch onto and penetrate human cells. Most of the mutations we've seen so far represent tweaks to these spikes, which means it only takes a minimal change within any of the few viral genes that control the spikes to create a newly threatening mutation.

But even when a virus hits the jackpot with a mutation that sharpens its ability to wreak havoc, that doesn't mean a dangerous new variant has emerged. To become a significant variant, a mutated virus has to out-replicate the far more numerous copies of the virus that already predominate in the population, and to do that it needs features that give it big advantages.

What specific features will help the mutation become a better replicator and spreader in the population is determined by the environment. For example, in the case of a respiratory virus like COVID-19, the ability to travel longer distances in the air, and to latch more firmly onto cells in the nasal passage, would likely make a new strain a better contender to become a widely spreading variant.

"A virus' job is just to keep propagating," says Green. "Any mutation that helps the virus survive and spread will make it more successful as a variant."

All told, the chances that a virus in the population will produce a much more dangerous variant in the course of a year would normally be extremely low. But when billions of people are infected with billions of copies of a virus, all bets are off. Thanks to Delta's infectiousness, and the huge number of people whose refusal or inability to get vaccinated leaves them primed to become living COVID-19 mutation labs, the conditions are ripe to produce yet more, potentially more dangerous, variants in the coming months.

"It's going to be very difficult to stop it from happening with masks and social distancing at this point," says Preeti Malani, a physician and infectious disease researcher and chief health officer at the University of Michigan. "Vaccines are the key, and vaccine hesitancy is the obstacle."

The growing number of people with natural immunity, from having recovered from COVID-19, won't save the day either, says Eric Vail, director of molecular pathology at Cedars-Sinai Medical Center. "At best it's now a third of the U.S. population with natural immunity, and that may be an overestimation," he says. "It won't be enough to guarantee that Delta will be the last big variant."

The most likely way a new variant will plague us is the same way the U.K. variant did earlier this year, and Delta is now: by being more transmissible. At first glance, that seems a tall order, given that Delta is already one of the most transmissible viruses ever encountered, falling short only of the measles. Then again, notes Osterholm, scientists thought the original COVID-19 virus was a shockingly adept spreader, only to be surprised by how much more easily the U.K. variant spread, just to be caught off guard yet again with the rise of Delta, which is about five times more transmissible than the original.

There's no reason to assume Delta represents any sort of ceiling in infectiousness. "I wouldn't be incredibly surprised if something else came along that's even more transmissible," says Vail. Such a super-spreading virus might burn through the unvaccinated, non-previously infected population so fast that hospitals couldn't come close to coping.

Making that possibility more likely is the fact that sheer transmissibility, more than any other characteristic a virus might acquire through mutation, confers the greatest advantage on a variant when it comes to outcompeting other versions. "If a mutation comes up anywhere that's more transmissible, it will be selected out to propagate," says Green. That means a single ultra-transmissible mutation popping up anywhere in the world in a single infected person could be enough to unleash a fresh round of heightened global misery.

Might a new variant get around the vaccine? Delta appears to be able to infect the vaccinated more readily than previous variants, reducing the major vaccines' effectiveness at preventing infection from about 95 percent to around 90 percent. (A recent Israeli study claimed the Pfizer vaccine's effectiveness plunges to 39 percent, but experts caution that the finding is an outlier that may not hold up.)

Most of the COVID-19 vaccines work by getting human antibodies to target the spike proteins on the virus. But because mutations can slightly change the shape of the spike protein, they can potentially disguise it from some of those antibodies, thus weakening the vaccine's effectiveness. The different variants have different combinations of mutations in the spike protein, and while so far none of those combinations seem to do a great job of disguising the spike protein enough to get around the vaccine, some seem able to chip away at its effectiveness. Delta has three mutations that together seem especially good at keeping the spikes under the antibodies' radar, leading to the breakthrough infections.

Still, the vaccines remain highly effective in preventing Delta from causing severe illness leading to hospitalization or death, to judge by the fact that 99 percent of the patients struggling with COVID-19 in U.S. intensive-care units are unvaccinated.

COVID-19 may well continue to evolve into new, widely spreading variants, but there's reason to think that none of them are likely to routinely blow past the immune defenses conferred by vaccine, and even the lesser natural-immunity defenses. One reason, notes Vail, is that the vast majority of COVID-19 virus in circulation is in unvaccinated people who weren't previously infected, and mutations that can avoid immunity have no real advantage in that environment. An immune-evading variant would be more likely to thrive in a population of vaccinated or recovered people, where such a mutation would allow it to outcompete non-mutated viruses—but there just isn't enough virus circulating in that population to allow for rapid mutation.

That's how Delta emerged, notes Vail. "There were four variants that arose in India, and three of them had some ability to evade immunity," he says. "The fourth one was Delta, which didn't have as strong an evading mutation, and that's the one that spread."

Green points out a second reason being immune-evasive will be a huge challenge to COVID-19: The human immune system, once it's activated by vaccination or infection, is more resilient and effective than even most studies indicate. That's because studies tend to focus on how the virus fares against antibodies specifically developed by the body to fight the virus, as observed in test tubes. In real life, the body rolls out other weapons, including innate antibodies that target a broader array of pathogens, and T-cells that only kick in when an infection starts to take hold—both of which most lab studies can't easily measure. More thorough studies are underway, says Green, and the results should aid in the development of booster shots that will help block Delta and possible future variants.

The mechanics of mutation also work in our favor when it comes to dodging future variants that cause more severe illness. It's not that such mutations can't or won't spring up in the coming months. Rather, it's that causing the infected to be extremely ill takes them out of circulation, so they can't spread the more-sickening variant. That means the variant would be at a disadvantage to competing forms of the virus that leave most of the infected feeling well enough to walk around and transmit the infection.

A particularly dangerous scenario would be a variant that left people feeling well for a long time, and then lowered the boom later with severe illness. But few viruses—HIV being one exception—master that trick, and so far that doesn't seem to be a threat from COVID-19, either.

Eisen warns that such delayed-illness scenarios can't be ruled out, either. There are ways new variants could inflict worse damage without compromising their ability to spread. For example, a new variant might attack the brain, heart or other organs in more subtle, slower ways that leave victims walking around but that eventually take a large toll.

"We've already seen that different variants have differing abilities to enter some types of cells, and that might have an effect on the nervous system or lung function," says Eisen. "It's very concerning."

Malani notes that there's anecdotal evidence that more young people are getting severely ill with Delta than has been the case with previous variants. That uptick may just be due to higher numbers of young people getting infected, or it may indicate a troubling shift toward greater vulnerability among the younger. That wouldn't be a first: The 1918 flu pandemic preferentially killed younger adults.

It's not yet clear whether or not Delta is hitting the younger harder. "It's a mystery right now," Malani says. "Infected young people might walk around for days or even weeks even though they're feeling very poorly, so it's hard to judge." But even if Delta isn't targeting the younger, a spin-off variant might.

While increased infectiousness is the most likely path for a fierce post-Delta variant versus getting past vaccines or causing more severe illness, there's a catch: Such traits aren't mutually exclusive. Simply as a matter of chance, a mutation that confers increased transmissibility might also cause more damage to health or give the virus a better chance at slipping past the defenses conferred by a vaccine. Although these latter traits aren't likely to be selected on their own, they could ride the coattails of a transmissibility-boosting mutation. "There's nothing to stop them from happening at the same time," says Eisen.

Fortunately, there's a built-in impediment to what might otherwise be a potentially endless march toward ever-more-dangerous variants: The virus will at some point run out of ways to become nastier, thanks to the relatively simple structure of the spike protein, which can only be mutated in a few hundred different ways, most of which won't make the virus more harmful. "There are only so many changes that can be made to the spike protein without making it non-functional," says Vail. "I'd be cautious about saying that it can keep mutating indefinitely."

Another big break: Unlike the flu virus, SARS-CoV-2 doesn't have a structure that lends itself to mixing and matching genetic material between different variants. That "recombination" capability is what helps make the flu a moving target each year for vaccines.

Like the flu, COVID-19 is probably going to be with us for the foreseeable future. But a big pickup in vaccination rates would at least put the age of the most dangerous variants behind us. At that point, says Green, we can focus on occasional new vaccines or booster shots that make the virus a relatively tame threat.

"I don't think eradication is on the table," she says. "But I think we could come up with something that's better than what we have now for the flu."

On the other hand, notes Green, the flu kills as many as 60,000 people a year. If COVID-19 keeps mutating away from vaccine effectiveness and natural immunity, and a large portion of the population continues to neglect vaccinations, then we'll indeed end up permanently haunted by the virus.

In that case, we'd be lucky if COVID-19 "only" kills tens of thousands every year. Thanks to the ongoing threats of variants, we might be in for a lot worse.

The lambda variant may evade vaccines, spread fast, new paper says

Deseret News 03 August, 2021 - 06:51pm

The lambda variant might be more transmissible and be strong enough to avoid vaccines.

The lambda variant of the coronavirus may be highly infectious and more resistant to COVID-19 vaccines than the original variant of the coronavirus, Reuters reports.

A new study — published online through bioRxiv but has not been peer reviewed — found that the lambda variant has three mutations to the spike protein that help it resist antibodies created by the COVID-19 vaccines

The study said that there were two additional mutations that make lambda even more infectious.

The researchers warned that the lambda variant should be labeled a “variant of concern” by the World Health Organization and not a “variant of interest,” as it is now.

Per Reuters, it’s unclear if the lambda variant is more dangerous than the delta variant right now. But senior researcher Kei Sato, of the University of Tokyo, told Reuters that we should be concerned about the variant.

Indeed, the variant is behind 1,000 different cases in the United States right now, according to Newsweek. The variant was original discovered in Peru in August 2020 where it became the dominant strain of the virus. It has since spread to 29 different countries.

Dr. S. Wesley Long, medical director of diagnostic biology at Houston Methodist, told USA Today that the lambda variant might not be as concerning at the delta variant.

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