POST 208. October 22, 2021, CORONAVIRUS. “What is the “delta plus” variant?” Scientists are monitoring the delta-related variant — known as AY.4.2. — to see if it might spread more easily or be more deadly than previous versions of the coronavirus.

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“What is the “delta plus” variant?

It’s a relative of the delta variant, identified by British scientists last month.

Because it isn’t a variant of interest or concern, it has not yet been officially named after a letter of the Greek alphabet, like the other worrisome variants.

Scientists are monitoring the delta-related variant — known as AY.4.2. — to see if it might spread more easily or be more deadly than previous versions of the coronavirus. In a recent report, U.K. officials said this variant makes up 6% of all analyzed COVID-19 cases in the country and is “on an increasing trajectory.”..

“Delta is dominant, but delta is evolving,” she said, adding that the more the virus circulates, the greater chances it has to mutate.

The U.N. health agency is currently tracking 20 variations of the delta variant. The AY.4.2 is “one to watch because we have to continuously keep an eye on how this virus is changing,”…

In the U.S., the delta variant accounts for nearly all COVID-19 cases. The newer “delta plus” variant has been spotted “on occasion,” but it’s not yet a concern, health officials said.” (A)

“U.K. government health officials have said it’s too early to tell whether the mutation poses a greater risk to public health than the delta variant, which itself is significantly more infectious than the original Covid-19 strain (and its successor, the alpha variant)…

Viruses constantly mutate and the coronavirus that emerged in China in late 2019 has gone through multiple minor variations that have made it virus more infectious and effective at spreading. This was first seen with the alpha variant (first sequenced in the U.K.) that went on to spread globally before it was usurped by the even more transmissible delta variant that was first discovered in India.

Delta, which was dubbed a “variant of concern” by the World Health Organization in May, remains globally dominant…

AY.4.2 is being identified in an increasing number of U.K. Covid cases, with some suggesting it could be a factor in the country’s growing health crisis that has prompted some doctors to call for Covid restrictions to be reimposed.

“This sublineage is currently increasing in frequency,” the U.K.’s Health Security Agency said last week, noting that “in the week beginning 27 September 2021 (the last week with complete sequencing data), this sublineage accounted for approximately 6% of all sequences generated, on an increasing trajectory. This estimate may be imprecise … Further assessment is underway.”

The U.K. is currently seeing a prolonged and worrying spike in Covid cases, reporting between 40,000-50,000 new infections per day in the last week, prompting experts to question why the U.K. is so vulnerable to Covid right now.

The delta subtype is reported to be 10-15% more transmissible than the standard delta variant, but it is too early to say for certain whether it has been causing a spike in cases in the U.K…

Health officials are remaining calm about the delta subtype, for now, noting that it’s crucial to keep an eye on the mutation but not to panic.

Commenting on “delta plus” on Wednesday, U.S. CDC Director Rochelle Walensky noted that “in particular the AY.4.2 variant has drawn some attention in recent days.” She added that: “we have, on occasion, identified this sub lineage here in the United States, but not with recent increase frequency or clustering, to date.”..

Andrew Pollard, head of the Oxford Vaccine Group, which helped to developed the AstraZeneca-Oxford University vaccine, said on Wednesday that the delta subvariant won’t change Covid picture.

“Discovery of new variants is of course important to monitor, but it doesn’t indicate that that new variant is going to be the next one to replace delta,” Pollard told BBC radio, Reuters reported.

“Indeed even if it does, delta is incredibly good at transmitting in a vaccinated population and a new one may be a bit better but it’s unlikely to change the picture dramatically from where we are today.”

Meanwhile, professor of immunology at Imperial College London, Danny Altmann, told CNBC Monday that the subtype “needs to be monitored and, so far as possible, carefully controlled.”

“Because delta has now been the dominant mutant in several regions for some six months and not been displaced by any other variants, the hope has been that delta perhaps represented [the] peak mutation performance achievable by the virus. AY.4 may be starting to raise doubts about this assertion,” he warned.” (B)

“Officials are keeping a close watch on a new descendant of the Delta variant of Covid that is causing a growing number of infections…

So far, there is no indication that it is considerably more transmissible as a result of these changes, but it is something experts are studying.

The mutations – Y145H and A222V – have been found in various other coronavirus lineages since the beginning of the pandemic.

Scientists are constantly checking for new genetic changes that Covid is undergoing.

Some emerging variants are worrying, but many are inconsequential. The difficult job is spotting, tracking and managing the ones that could matter.

The UK is a front-runner in carrying out these vital lab analyses, having completed more than a million tests so far.

The first step is to pick up new mutants worth watching, such as this new offshoot – AY.4.2.

Next, if there is a strong suggestion that the genetic changes might make the virus more contagious, it is classified as a variant under investigation and more checks are done.

If it becomes clearer that it could be more transmissible and escape some of the built up immunity from past infections or vaccines, or potentially cause more serious disease, it is moved into the variant of concern category. That’s the one Delta belongs to.

At this stage, experts don’t think AY.4.2 is likely to take hold – so in time it could well burn out and drop off the watch list.

Prof Francois Balloux, director of University College London’s Genetics Institute, said: “It is potentially a marginally more infectious strain.

“It’s nothing compared with what we saw with Alpha and Delta, which were something like 50 to 60 percent more transmissible. So we are talking about something quite subtle here and that is currently under investigation.

“It is likely to be up to 10 percent more transmissible.

“It’s good that we are aware. It’s excellent that we have the facilities and infrastructure in place to see anything that might be a bit suspicious.

“At this stage I would say wait and see, don’t panic. It might be slightly, subtly more transmissible but it is not something absolutely disastrous like we saw previously.”” (C)

“A new and potentially more transmittable version of the Delta variant has entered Israel just as the COVID infection rate has started to decline and the country prepares for flu season. Is the variant known as AY4.2 a reason to sound the alarms?

According to the Health Ministry, a single case of AY4.2 was identified in Israel in an 11-year-old boy who recently returned from a trip to Moldova. The boy tested positive for coronavirus while in isolation, the ministry said, and so far, it does not appear that others were infected…

“The variant was enough to catch the attention of former Food and Drug Administration commissioner Dr. Scott Gottlieb, who tweeted about the situation over the weekend.

“UK reported its biggest one-day Covid case increase in 3 months just as the new delta variant AY.4  with the S:Y145H mutation in the spike reaches 8% of UK sequenced cases,” he wrote. “We need urgent research to figure out if this delta plus is more transmissible, has partial immune evasion?”

The variant has been in the UK since about July, he said, but it has been slowly increasing in prevalence.

“There’s no clear indication that it’s considerably more transmissible, but we should work to more quickly characterize these and other new variants. We have the tools,” he said. “This is not a cause for immediate concern but a reminder that we need robust systems to identify and characterize new variants. This needs to be a coordinated, global priority for COVID, the same as similar international efforts have become standard practice in influenza.”…

The development of variants is a natural process, Sorek and Cohen said.

“Think about an article you are writing, and in the article, there are 30,000 letters – more or less the number of letters in the genome of Sars-CoV-2,” Cohen explained. “You are copying and pasting that article by hand, so at some point, the more you copy it, the more likely you will make a mistake.”

These mistakes are mutations. When the mistake replicates and starts to spread, this becomes a new variant.

The variants compete with each other to survive. Those that develop advantages, such as being more transmittable, will become more robust, while the others will become extinct….

In Israel, the Health Ministry is reporting between 1,000 and 2,000 new coronavirus cases a day, but it does not report which variants are tied to those cases. Cohen said that if one boy brought AY4.2 into Israel, it is likely that others have, too, but they may be asymptomatic or did not undergo genetic sequencing yet.

“There may also be other variants we are not aware of,” he said.

The Health and Tourism ministries are preparing to open up to vaccinated tourists beginning sometime next month, they have said. Cohen said he is supportive of the move, but that the country must remember “there is no free lunch.”

“To some extent, what is the difference if a tourist or an Israeli citizen is entering the country from abroad?” Cohen asked. “If both are vaccinated, it is just more of the same.”

He said he does not expect a major change in the probability per person to get new infections when the skies further reopen. However, he added that from the moment the number of people entering Israel is higher, “we multiply the chances of having new variants.

“We need to be aware of what is going on in Israel,” Cohen said, but when it comes to stopping the entry of new variants, short of shutting the airport again, “there is not much that we can do.”” (D)

The emergence of new SARS-CoV-2 variants that can spread rapidly and undermine vaccine-induced immunity threatens the end of the COVID-19 pandemic.

The delta variant (B.1.617.2) emerged in India and subsequently spread globally within a short time period. Also in Germany, almost all recent infections are due to this variant. In addition to Delta, so-called Delta Plus sub-variants have been observed, which carry additional mutations that may make them more dangerous…

“Our studies show that heterologous vaccination induces significantly more neutralizing antibodies to Delta than two vaccination shots with Oxford-AstraZeneca. Individuals who have received such a heterologous vaccination may have a very good immune protection against Delta and Delta Plus,” says Markus Hoffmann.

“Our results are consistent with the observation that vaccination efficiently protects against development of severe disease after infection with the Delta variant, but frequently fails to completely suppress infection. In light of the efficient protection against severe disease, the goal continues to be a high vaccination rate. This can prevent the health care system from being overwhelmed in case of increased spread of Delta and closely related viruses during the winter months,” says Stefan Pöhlmann.” (E)

Can new variants of the coronavirus keep emerging?

Yes, as long as the virus that caused the pandemic keeps infecting people. But that doesn’t mean new variants will keep emerging as regularly, or that they’ll be more dangerous.

With more than half the world still not vaccinated, the virus will likely keep finding people to infect and replicating inside them for several months or years to come. And each time a virus makes a copy of itself, a small mutation could occur. Those changes could help the virus survive, becoming new variants.

But that doesn’t mean the virus will keep evolving in the same way since it emerged in late 2019.

When a virus infects a new species, it needs to adapt to the new host to spread more widely, says Andrew Read, a virus expert at Pennsylvania State University.

According to the Centers for Disease Control and Prevention, the delta variant is twice as contagious as earlier versions of the virus. And while it could still mutate to become more infectious, it probably won’t double its transmission rate again, says Dr. Adam Lauring, a virus and infectious disease expert at the University of Michigan.

“We’ve seen a stage of rapid evolution for the virus. It’s been harvesting the low-hanging fruit, but there’s not an infinite number of things it can do,” Lauring says.

It’s possible that the virus could become more deadly, but there isn’t an evolutionary reason for that to happen. Extremely sick people are also less likely to socialize and spread the virus to others.

Experts are watching to see whether emerging variants could be better at evading the protection people develop from vaccination and infections. As more people get the shots, the virus would have to be able to spread through people who have some immunity for it to survive, says Dr. Joshua Schiffer, a virus expert at the Fred Hutchinson Cancer Research Center.

“The virus could take on a mutation that makes the immune response less effective,” he says.

If that happens, scientists may recommend that vaccine formulas be updated periodically, just as annual flu shots are.” (F)

“The coronavirus could shift in countless ways, but there are three concerning possibilities: It could become more transmissible, it could become better at evading our immune system or it could become more virulent, causing more serious disease…

Delta appears to evade some antibodies, but there are other variants, particularly Beta, that are even better at dodging these defenses. For now, Delta is so infectious that it has managed to outcompete, and thus limit the spread of, these stealthier variants.

But as more people acquire antibodies against the virus, mutations that allow the virus to slip past these antibodies will become even more advantageous. “The landscape of selection has changed,” said Jessica Metcalf, an evolutionary biologist at Princeton University. “From the point of view of the virus, it’s no longer, ‘I just bop around, and there’s a free host.’”

The good news is that there are many different kinds of antibodies, and a variant with a few new mutations is unlikely to escape them all, experts said.

“The immune system has also evolved to have plenty of tricks up its sleeve to counteract the evolution of the virus,” Dr. Pepper said. “Knowing that there is this complex level of diversity in the immune system allows me to sleep better at night.”…

Eventually, as viral evolution slows down and our immune systems catch up, we will reach an uneasy equilibrium with the virus, scientists predict. We will never extinguish it, but it will smolder rather than rage.

What that equilibrium point looks like exactly — how much transmission there is and how much disease it causes — is uncertain. Some scientists predict that the virus will ultimately be much like the flu, which can still cause serious illness and death, especially during seasonal surges.

Others are more optimistic. “My guess is that one day this is going to be another cause of the common cold,” said Jennie Lavine, who explored that possibility as an infectious disease researcher at Emory University.

There are four other coronaviruses that have become endemic in human populations. We are exposed to them early and often, and all four mostly cause run-of-the-mill colds.

Covid-19 might just be what it looks like when a novel coronavirus spreads through a population without any pre-existing immunity. “This may not be such a different beast than everything else that we’re accustomed to,” Dr. Lavine said. “It’s just a bad moment.”

Of course, plenty of uncertainties remain, scientists said, including how long it will take to reach equilibrium. With infections beginning to decline again in the United States, hopes are again rising that the worst of the pandemic is behind us.

But much of the world remains unvaccinated, and this virus has already proved capable of surprising us. “We should be somewhat cautious and humble about trying to predict what it is capable of doing in the future,” Dr. Crotty said.

While we can’t guard against every eventuality, we can tip the odds in our favor by expanding viral surveillance, speeding up global vaccine distribution and tamping down transmission until more people can be vaccinated, scientists said.

The actions we take now will help determine what the coming years look like, said Dr. Jonathan Quick, a global health expert at Duke University and the author of “The End of Epidemics.”

The future, he said, “depends much, much more on what humans do than on what the virus does.”” (G)

“Pfizer’s chief executive, Albert Bourla, made a bold promise in June. Standing next to US President Joe Biden at a press conference in St Ives, UK, just before the G7 summit meeting, Bourla said that should the need arise for a new COVID-19 vaccine, his company could get one ready within 100 days.

The need he was referring to is the possible emergence of an ‘escape variant’ — a dominant strain of SARS-CoV-2 that evades the fledgling immunity established through vaccines and previous infections. No such strain has yet been identified, but Pfizer and other leading COVID-19 vaccine makers are gearing up for that scenario.

What does it take to be nimble enough to design and test an updated vaccine against an unknown viral strain, in record time? Nature spoke to three COVID-19 vaccine makers — Pfizer, Moderna and AstraZeneca — to find out exactly how they are preparing.

Over the past few months, all three companies have been running dress rehearsals by practising on known SARS-CoV-2 variants. This involves updating their vaccines to match variants such as Beta and Delta, testing them in clinical studies, tuning their internal workflows and coordinating with regulators. Their goal is to learn from these warm-up trials and smooth out kinks in their processes, so that they can move fast if, or when, a true escape variant emerges.

“At some point, inevitably, we’re going to have to make variant vaccines — if vaccines are the way population immunity will be maintained — but we’re not at the point where we can confidently predict the evolution of the virus,” says Paul Bieniasz, a virologist at the Rockefeller University in New York City. “Practising with existing variants seems like a reasonable approach.”…

Determining the true efficacy of variant vaccines will be difficult. In regions where COVID-19 vaccine trials are well established, it can be hard to find volunteers who have not yet received a vaccine, yet are willing to enroll in an experimental trial of a new one. There might also be ethical concerns around recruiting placebo groups for randomized controlled trials, given that effective vaccines are available….

How public-health authorities will determine that a variant has escaped — and therefore the world needs a new COVID-19 vaccine — isn’t yet clear. Pangalos offers one way to measure that: “If we start to see lots of people going into the hospital that have been vaccinated, then we have a problem,” he says. “But right now, we’re nowhere near that.”

The World Health Organization has a regimented process for determining when and how to change an influenza vaccine to match an emerging strain. These decisions are based in part on a long history of monitoring and immunizing against the virus’s evolution. “That doesn’t exist for COVID,” says Hepburn.

Miller hopes that the process of updating a COVID-19 vaccine will eventually become as streamlined as changing a flu vaccine, which typically doesn’t require much in the way of clinical studies. And because RNA vaccines can be manufactured more quickly than conventional jabs, she adds, “the idea would be to make that switch even more rapidly than we’re able to do with flu”. (H)

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