The Third Wave Coronavirus Mutants Are Spreading Fast

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BERLIN, GERMANY - JANUARY 30: Children enjoy snow during the second wave of the coronavirus pandemic on January 30, 2021 in Berlin, Germany. Authorities extended the current hard lockdown till February 14 as daily Covid-19 infection rates and deaths remain high. (Photo by Maja Hitij/Getty Images)

The coronavirus mutants are spreading at breakneck speed in Germany. They have left puzzled researchers asking what makes them so highly infectious? And why are they infecting so many young people in Israel?

By Rafaela von Bredow und Veronika Hackenbroch

We can’t take it anymore, raged Sonja Ultsch in a video on Facebook last week. “We’ve already let them slap us on the left cheek for Ischgl, now we have to turn our right cheek, too!” It was a reference to the Austrian ski town that was responsible for one of the biggest outbreaks of the novel coronavirus in Europe during the first wave last year.

As if in a commercial for pleasant skiing holidays, the hotelier filmed herself against a sunlit Alpine backdrop, railing against the Austrian government’s efforts to seal off Tyrol because of a major outbreak of the South African B.1.351 virus mutant in the region. “I’ve had it, let them lock us in!” Ultsch railed, her eyes hidden behind sunglasses along with pink lipstick and light blond hair. “But then we’re going to open everything here!”

The defiant video went viral, and Ultsch certainly spoke from the heart of many a Tyrolean. And not only them. There is probably no country in the world where people aren’t fed up with the lockdown, which has transformed from an emergency measure to an entire new way of being. The frustration and suffering is growing louder because of the pandemic’s depressing and seemingly nonstop reign.

And ever since the virus mutants began spreading around the globe, even the last motivation for bravery is fading: the hope that the nightmare will soon end thanks to vaccination. Because as incredibly fast as it was possible to find and produce vaccines, the mutants were faster. And they are still faster.

For physicist and mathematician Michael Meyer-Hermann of the Helmholtz Center for Infection Research in Braunschweig, one thing is clear: “Vaccination isn’t going to help us slow down the momentum of infections until the younger population has been immunized.” And what about higher temperatures in the spring and summer? It might help a bit, Meyer-Hermann thinks, when people start spending more time outside. “But that alone will in no way suffice.”

Meaning that the virus could continue to run rampant until enough people have been vaccinated.

In addition, the South African and Brazilian variants have some particularly nasty characteristics. For one, it’s likely they can re-infect people who have already suffered from an infection with the original coronavirus. And the vaccines also appear to be weaker against the new strains.

It’s like a whole new pandemic has begun with the mutants. Things had been looking pretty good in Germany: The incidence rate was falling and continues to fall, and the measures seem to be working. But now, still invisible in the mountain of case numbers, the highly contagious mutants are spreading, most notably B.1.1.7, the virus variant that overran the United Kingdom in a matter orfweeks and led Portugal to have the highest incidence levels in the world. It will inevitably dominate infection trends in Germany, as well. The question is no longer whether the dangerous mutants will run rampant, only when.

This puts politicians in a bind. They are being forced to position themselves somewhere between two extremes, with one just as nightmarish as the other. On the one hand, you have the eternal lockdown, from which it is only ever possible to briefly emerge. On the other, by loosening up the measures, you risk giving the mutants free rein, which could push the case numbers in this country into the tens of thousands every day with many fatalities, including younger victims, people with long-term symptoms and constant series of new virus mutants.

Because this is also clear: High infection rates and increased numbers of people available for the virus to attack mean the virus can multiply freely. And with each replication, the likelihood increases of new mutations emerging. In most cases, more harmless, but also some more dangerous ones or even variations that are resistant to vaccines.

What, then, is the country facing? It’s as if the pandemic has transported us into a weird state of limbo where people who are already pandemic-weary, frustrated and angry are granted a brief respite in which everything now depends on how they behave and decide to act.

It is possible to stop the mutant through a hard lockdown, as we are currently seeing in the UK and Ireland. But it is not possible to sustain that lockdown until a larger proportion of the population finally gets vaccinated in the summer or autumn. How much opening, then, is possible without the situation spinning out of control again? Scientists and politicians around the world are currently wrestling with that question. Last Wednesday, German Chancellor Angela Merkel and the governors of the country’s 16 states debated the issue.

The federal government and the governors decided to extend the current lockdown until early March, with restrictions placed on social contacts, social distancing and bars. Restaurants have been ordered to stay closed until at least March 7. The only rule to be loosened is that hairdressers can open their doors to customers again at the beginning of March. The German states will decide on their own when to reopen schools.

Ultimately, the politicians had to yield, at least in part, to the findings of scientists worldwide who are rushing to do research on the new mutants. The calculations of epidemiologists, in particular, predict a disaster if a relaxation of rules were to take place now, even if it were at primary schools.

Still, that didn’t prevent individual governors from causing the usual local chaos in loosening the lockdown rules the day after the federal and state decisions were made. Just an example: On Saturday, flower shops were allowed to reopen in Lower Saxony. They were allowed to open in Bavaria on Sunday, too, but only because it was Valentine’s Day. On March 1, the northern state of Schleswig-Holstein will allow garden centers, zoos and nail studios to reopen.

“The current measures aren’t even sufficient for stopping the exponential spread of the new variant,” says Meyer-Hermann of the Helmholtz Center for Infection Research. The physicist plugged all the basic assumptions available about the new variants into his models and calculated how they would affect the development of infections.

What he’s saying is that a third wave is coming.

Beyond Meyer-Hermann’s models, the figures from neighboring countries also show what will happen in Germany. British researchers have created an animation showing Britain divided into counties. It shows how B.1.1.7 starts in the south, soaking the country in a pale pink all the way up to the north until it becomes deep violet at lightning speed in the disease’s march to victory.

The UK example also shows how hard the lockdown has to be in order to stop the mutant’s spread. And in Israel, we are currently seeing how the virus can evade even an aggressive vaccination strategy. It appears that it then just starts infecting more children – another unpleasant finding.

The numbers illustrating the success the B.1.1.7 mutant has had are quickly outdated. The week before last, the Robert Koch Institute, Germany’s center for disease control, reported that the share of the British variant in Germany was just under 5.6 percent. By last Thursday, though, that figure had doubled to 11.2 percent. Less than a week later, it had almost doubled again to over 20 percent.

On Thursday, the city of Düsseldorf announced that B.1.1.7 had been detected in every fifth infected person there. An outbreak had occurred in a homeless shelter, among other places. In the northern German town of Flensburg, about one in three infections with SARS-CoV-2 was an infection with the British variant. And in the northern Bavarian regions of Hof, Wunsiedel and Tirschenreuth, the proportion of new mutants in the positive tests is already at 40 to 70 percent.

In Cologne, too, at the initiative of Florian Klein, director of the Institute of Virology at the city’s university hospital, all positive coronavirus samples are currently being examined for the new variants using a special PCR test. Right now, B.1.1.7 accounts for around 15 percent of all cases and the South African mutant for around 5 percent.

But the increase didn’t surprise the virologist. “There is no reason to assume that developments in Germany should be fundamentally different from those in other countries,” says Klein.

The latest figures indicate that the mutant from the UK currently has a reproduction number of 1.3, meaning that 10 infected people spread the disease to 13 others. “Then the number of cases doubles about every one to two weeks,” calculates physicist Viola Priesemann. If it were to stay that way, there would be more than 30,000 new infections a day in Germany again after Easter, despite the extension of the lockdown.

“According to our predictions, if you were to relax the (lockdown) rules now, then one would expect that B.1.1.7 would be dominant sometime in March,” says modeler Meyer-Hermann. Dominant means that the mutant would account for half of all infections.

It’s still not clear exactly why B.1.1.7, but also the South African and Brazilian variants, manage to infect so many people so easily. However, virologists have identified the mutation that enables the pathogen to do so: It’s called N501Y and it affects the binding of the virus to host cells. According to the initial findings, it helps the pathogen infect a human being in a significantly shorter amount of time. As such, the definition of what can be described as a close contact may have to be changed.

Initially, it appeared that the new variants were killing disproportionately more than the previous SARS-CoV-2 virus simply because they were infecting so many more people. More recent data, however, has led to the suspicion that they actually also cause more dangerous progressions of the disease. “There is a realistic possibility that infection with VOC (variant of concern) B.1.1.7 is associated with an increased risk of death compared to infection with non-VOC viruses,” stated a report by British government advisers in late January.

A lot will depend on how quickly vaccinations are now administered. In response, in the UK, where B.1.1.7 was first identified, the public health service has ramped up all systems, and just under one-fifth of the population has already been vaccinated. Clearly ahead in the vaccination race right now, though, is Israel, where 3.7 million people have already received their first dose of vaccine – 41 percent of the population. Meanwhile, in Germany, following the debacle surrounding the European Union’s vaccine orders, the government is promising to make “an offer of vaccination” to all adults by the end of summer.

The good news is that the vaccines available now provide reasonable protection against B.1.1.7, with minor declines in efficacy. But B.1.351 from South Africa and P.1 from Brazil, the so-called escape mutants, are proving to be more of a problem. The two SARS-CoV-2 variants each have another mutation in their genome: E484K. As if in some horror movie, American infectious disease specialists are now calling it the “eeek mutation.”

Experiments conducted in South Africa have shown that it helps the virus trick its victims’ immune systems. Researchers there mixed the mutated viruses with the blood serum of patients who had recovered from COVID-19. It turned out that the antibodies were only able to render the mutants harmless to a small extent, meaning the South African mutant could infect people who have already been sick with COVID-19 or were at least infected with SARS-CoV-2. In other words, people who were believed to have immunity. But this also means that treatments using monoclonal antibodies will no longer work as well. And that vaccines currently available are less reliable.

“The vaccines that were designed for the previous variants will lose effectiveness,” says Alex Sigal, who heads a branch of the Berlin Max Planck Institute for Infection Biology in Durban, South Africa. “This has been shown most dramatically with AstraZeneca’s vaccine.”

The vaccine had only 10 percent efficacy left, although these are preliminary and not representative results. “The solution is the redesign of the vaccines targeting the new variants,” says Sigal. “What we are checking now is to see if antibodies to the new variants are cross protective, that is they can target both old and new,” he says. “If yes, this might be a solution.”

And if not? How will we deal with them? And how alarming are these findings? Austria was hit hard by the wave of the coronavirus that emanated from the ski resort town Ischgl – it should be an example of what people had been hoping for: that people can become immune to SARS-CoV-2.

But rather than having developed herd immunity, it appears that the E484K mutation is also reinfecting people who had earlier strains of the coronavirus. That would mean that in Germany, as is now the case in Tyrol, small islands of infection could form again and again where the disease had already passed through with a high number of cases – in Saxony in the east, for example, which has been hard hit, or Heinsberg, the site of the first major outbreak in Germany last year, or Tischenreuth.

And it wouldn’t necessarily take the South African or Brazilian variant for that to happen. Evolution seems to favor escape mutations everywhere where many immune systems are already armed against the previous, more harmless SARS-CoV-2. In Britain, B.1.1.7 has also further mutated to acquire the “eeek mutation,” with which it may be able to reinfect people who have recovered from a previous coronavirus infection.

“We have already seen 28 cases of B.1.1.7 with the E484K mutation to date in Britain,” says Jeffrey Barrett of the Wellcome Sanger Institute in Cambridge, where more than 60,000 positive virus samples have been sequenced and analyzed since December. The mutation has now occurred at least three times independently. “Viruses are always mutating,” Barrett says. “The appearance of a worrisome mutation like E484K on top of the B.1.1.7 variant was inevitable.”

That’s exactly what can happen if vaccination is as slow as it is in the European Union, but where high infection rates are still raging: SARS-CoV-2 is adapting. That’s why it’s so important to keep the number of “new infections as low as possible everywhere in the world,” says Barrett.

So how smart is it in a situation where you have a high infection rate like the one seen in Germany to reopen schools for in-class teaching, as the eastern state of Saxony did this week? Or as other states are planning on doing in March? “By doing so, we risk letting B.1.1.7 slip out of our control,” warns Meyer-Hermann of the Helmholtz Institute for Infection Research. “Because then we won’t get into the low case rate zone in time.”

It is indisputable that schools, like any place where many people meet, contribute to the incidence of infection. Most recently, a large representative study of Austrian schools showed that children are just as likely to get infected as adults, including primary school pupils.

And since the mutants began their rampant spread around the world, another awful suspicion has been added to the list: that the new pathogens are increasingly infecting children. Tests in Corzano, for example, showed that 10 percent of the northern Italian municipality’s 1,400 inhabitants were infected with B.1.1.7 and that 60 percent of those infected were primary school- and day-care aged children.

In Israel, doctors with the Association of Pediatricians recently sent an alarming letter to the country’s health minister. They had found that more than 50,000 children and teenagers had tested positive for SARS-CoV-2 in January – the largest number ever, even more than in the first and second waves. Cyrille Cohen of Bar-Ilan University told the British Medical Journal that since mid-December, when B.1.1.7 emerged in Israel, the proportion of new daily infections among under-10-year-olds has risen by almost a quarter. Although the vaccines haven’t been approved yet for use in children, Israel now wants to become the first country to vaccinate risk patients under 16 years of age.

Schools, which were supposed to reopen as part of Israel’s successful vaccine campaign, remain closed. “It is my opinion that we should still reopen gradually,” Cohen told the British Medical Journal, “until we understand better the infection pattern of this new variant.”

Still undetected at the time in autumn, the mutant in England spread primarily through schools. Observers were astonished at the number of cases, which increased especially among children and adolescents. As the incidence continued to skyrocket in November, pubs and restaurants were closed, people were strongly encouraged to work from home and the number of social contacts allowed was restricted.

But even with all those measures in place, they were unable to stop B.1.1.7.

In Canterbury, in the southeast English county of Kent, the weekly incidence rose to around 600 cases per 100,000 inhabitants. “And other places around here were much higher,” reports a translator who has lived in Canterbury for years and keeps a close eye on the coronavirus situation.

It wasn’t until the strict “Tier 4” lockdown imposed by Prime Minister Boris Johnson just before Christmas in some regions that the tide turned. Many people are only allowed out of the house to buy groceries and rarely even go outside to get fresh air. “I haven’t been in the city center for ages,” says the translator.

The good news coming out of Britain is that it is possible to keep B.1.1.7 in check with strict containment measures. The number of cases has also fallen sharply in Ireland after strict lockdown measures there, as well. Schools and most stores in the country are closed. And people are only allowed to leave their homes if they have a valid reason.

“Everybody has found this lockdown very difficult,” says Patrick Mallon, a professor of microbiology at University College Dublin and a doctor of infectious disease at St. Vincent’s University Hospital. “The mental health toll is considerable.”

But he says the situation at his hospital has since eased noticeably. The real challenge, Mallon says, will be when it comes to relaxing the strict regime again. Will that even be possible with the new variant without the case numbers immediately shooting up again?

“No one really knows,” Mallon says. “It’s going to be an experiment.” He says it is important to get the number of cases down as low as possible.

That view is shared by the 14 scientists in Germany who have joined forces to form the “No Covid” initiative. With improved contact tracing in the public health departments – “faster and more automated” – Meyer-Hermann calculates that the reproduction number increased by the mutants to over 1 can be reduced, but not with the current high case numbers, according to the professor in Braunschweig. “That could be successful in the range of an incidence of 10” infections per week per 100,000 residents, he says.

Then the current measures, together with more efficient contact tracing, would make it possible to bring the reproduction number of B.1.1.7 down below 1.

But last Wednesday, German politicians voted against “No Covid,” at least for the time being. The only concession made to the idea of low case numbers is that the target is now 35 rather than the equally erratic and scientifically unfounded target of an incidence of 50 cases per week per 100,000 inhabitants.

The muddle of hair salon and school openings with contact restrictions continuing, however, makes it difficult to extend Meyer-Hermann’s curves toward spring. No one knows exactly what will happen now. But it is considered likely that in the end, it won’t just be a single variant that prevails. In addition to B.1.1.7, the South African and Brazilian variants are also likely to spread in Germany.

It is conceivable, for example, that B.1.351 will soon be found increasingly in southern Germany because of its proximity to Tyrol – and everywhere where many people are already immune to the earlier coronavirus.

“The more people that get vaccinated, the more likely it is that variants will spread in our country against which the vaccines aren’t as effective,” explains virologist Timm.

Vaccine manufacturers are already working at full speed on new vaccines that they hope will also be effective against the new variants. But when they are used, they also nudge the evolution of the virus correspondingly – and the more people in multiplies in, the faster that happens.

“Viruses evolve to survive,” says Dublin infectious disease specialist Mallon. That’s just what viruses do. “Unless you recognize and accept that, you will never be able to fight them successfully.”

Der Spiegel

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